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Progressive Licensing Workshop
Health Canada
November 27 - 28, 2006
Discussions on the Theme
(PDF Version - 377 K)
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Deepening our understanding of Canadians' values, issues, interests and priorities regarding a new drug regulatory framework.
Book of Discussion Reports
Table of Contents
List of Discussion Reports
The following 38 discussion reports were generated during the two-day workshop on a new drug regulatory framework, hosted by Health Canada.
Participants identified topics that were important to them, and then led discussions on the topics with others who were also interested. Participants came from across many different stakeholder groups - Health Canada, the pharmaceutical industry, patient and consumer groups, healthcare providers, and academia.
The topic initiator then transcribed the notes of these discussions into a report - they have not been edited, except for clarity around abbreviations and any problematic spelling.
Discussion Report # 1
Topic : Will PL be a burden to the industry, will it drive research = drugs from Canada?
Initiator: A. Christine Nestruck
Participants
Mike Patteson
Alison Maloney
Alison Vanlerberghe
Michelin Piquette
Monica Dhir
Ray Chepesiuk
Discussions, proposals, actions
- Canada is a tiny market.
- Reimbursement issues. Even if product is available, if it is not reimbursed, Canada will lose the product.
- Any access at the end of phase II, i.e. trials must be in line with global clinical trial requirements.
- Will there continue to be two independent, overlapping drug approval processes, i.e. HC and CDER. Lack of harmonization.
- What is the societal benefit of PL.
- Do we have the appropriate tools, processes to analyze risk and Benefit?
- Will there be an option for PL vs the current process. PL is not appropriate for all drugs.
- The possible burden to big pharma, small pharma, Canadian pharma and biotec is not the same?
- More emphasis of the acceptable requirements and considerations for Risk management plans is necessary.
- Don't create something uniquely Canada. Transparency and harmonization critical.
- Expectation vs. requirements. Transparency and harmonization critical
Discussion Report #2
Topic : What should Federal "approval" mean?
Initiator : Robyn Lim
Participants
Mike Tierney
Muna Idris
Michael Taylor
Mary-Anne Kent
Kim Dix
Patrick Cupido
Mike Ward
David Griller
Ken Potvin
Pier-Giorgio Fontana
Michael Hunt
Discussions, proposals, actions
Licensing of drugs: car analogy: similarities: emissions control standard, safety standards
Legal vs perceptual issues: people often perceive more (effectiveness/efficacy/safety) than there really is - political issues?
Certainty vs uncertainty:
Innovative drug - lower threshold for Efficacy / Safety; communicate the Safety / Efficacy / Quality
No metrics for effectiveness: how measure, what processes to measure? Problem.
NOC means Safety and Efficacy
Know the unknowns; Health Canada has the responsibility to follow through with other stakeholders on these issues; can't devolve responsibility
Can't separate health protection from giving access
Definition of Safety, efficacy, effectiveness
Positive Benefit Risk profile at given point in time/conditions of use: e.g. available therapies on market?, conditions?, breakthrough? Risks?
US: life-threatening diseases: theory re efficacy and not toxic and willing to pay for it
How communicate the qualifiers to patients, primary care?
Present appearance of Safety and efficacy
Black and white is unreasonable especially for life-threatening diseases
Possibility to improve primary care: encourage to follow protocol for "special drugs"
Qualifiers for exceptions vs for everything - caveat
Threshold for regulator comfort is so variable - can't capture in regulations; tools to manage threshold of recently approved drugs - restricted use.
Current regs are adequate to address threshold needs (labels help!)
Any rules around trial sizes?: No simple answers
Assume will work and be safe unless told by the physician... e.g. if not working properly after X time, then stop
For prescription: need learned intermediary: major role of prescribers
Over The Counter (OTC): read the instructions
Physician - patient shift in roles...
No notion that one size fits all, gradations, other stakeholders
Comfort level of reg. would be increased if given by specialists
e.g. electronic health record
unknowns- uncertainties -> still captured with this approach
Notice of Compliance with Conditions (NOC/c) is loose for users - define meaning and relate to labelling (borrow from Clinical Trials: requirement for protocols with restrictions for NOCC-type drugs)
NOCC: manufacturer, learned intermediaries: roles!
-protocols have to be part of it
e.g. clinical guidelines development
Q: how get efficacy? A problem
A: access only through trials for drugs with early release: a problem for patients!
Missing piece: manufacturer has to play by same rules - expansion of indications to physicians
Manufacturer has to come on board with regulation: how make regs all-inclusive? Market share...
Make it fair! : clean conditions, regulatory teeth: consequences
How engage?
Quality of data: Progressive Licensing: if more focus on specific life risks: there are colleges they need to play as well
Principle of where HC is at is fine: detail, flex: major challenges
First piece is not broken
Need effectiveness too
Life-cycle is good
Decision for access now based on paying for it - that is wrong too
"early access" make one person very unease: post market tragedies: safety is bottom line!; efficacy: relates to disease context
what is driving access?: innovation strategy (industry); access (industry, patients, inter-related sometimes); international trade issues too
Discussion Report #3
Topic : WHAT IS EFFECTIVENESS?
Initiator : Pierre Morin
Participants : Colleen Fuller, Jean-Pierre Grégoire, Maurica Maher, Paul Sauders, Mario Simard, David Skinner
Discussions, proposals, actions
Discussions:
Efficacy = clinical or theory
Effectiveness is post-market profile (comparative) for
Formularies and approvals for conditions of use
Could provide physicians with improved toolbox.
IMPEDIMENTS
Main difficulty is in collecting meaningful data.
recommandations
STICK TO MEASURING SAFETY
actions
Discussion Report #4
Topic : Access to drugs - low volume
Initiator : Gilbert Matte
Participants : Milan Patel, Ian MacKay
Discussions, proposals, actions
Issues: Improving access to drugs with limited volume of sale:
- radiopharmaceuticals,
- drugs withdrawn from the market
Discussion, proposals and actions.:
Definition of responsibilities:
From Health Canada: to insure drug availability and provide incentive From Manufacturer: to provide alternative or at least insure reasonable transition time when a drug is withdrawn.
Proposals and possible actions:
Identify low volume drug: committee of expert to review definition of Low volume drugs and review evaluation process for low volume drugs. Define a new drug category: with regulatory provisions for either the right of compounding, easier licensing (withdraw agents using older data). Provide incentive to manufacturers: tax incentive and submission cost rebate. International cooperation: Accept paper submission, lower fee, recognize other jurisdiction approval and put incentive for Canadian distribution Progressive licensing using older data when new data are not available due to either low market volume or ethical issues.
Discussion Report #5
Topic : Interpatient Variability in the Risk-Benefit Balance
Initiator : Levine
Participants : Levine; Lee; Berthiaume; Manthorne; Matte; Piquette-Miller; Askerow; Bouchard; Cantin
Discussions, proposals, actions
Recognition of the issues -
Risk-benefit assessments depend upon the perspective being adopted, i.e., regulator, health care provider, or patient. The regulatory process for drug approval is based upon a risk-benefit assessment from a population perspective. Nonetheless, drug effects in populations are actually the aggregate of the effects occurring in individuals that comprise the population. But the risk-benefit assessments (for a specific drug or intervention) will vary amongst individuals depending upon:
- What is the health issue of that particular patient, and where they are in the time line of the illness/health issue, i.e., primary, secondary or tertiary prevention.
- The genetic constitution of the patient, e.g., metabolic enzymes.
- The potential benefit of the drug (intervention),recognizing that not all persons will achieve the benefit and that benefit is measured as the incremental benefit from the usual and customary treatment in the absence of the drug (intervention).
- The risk knowledge available at the time of the risk-benefit assessment, recognizing that absence of risk information is of itself a risk by which a potential benefit may be measured.
In risk-benefit assessment there is no one risk and one benefit that are being weighed against each other. There are a basket of risks (known and unknown) and a basket of potential benefits, and which risk(s) and benefit(s) apply to any individual will vary from person to person resulting in different risk-benefit assessments.
All of this is done in a world of uncertainty. There is no absolute truth that can be ultimately identified, but rather decisions will have to be made from estimates or probabilities of risk-benefit assessment.
In moving from the current drug regulatory process to a new 'life cycle' system, there is a need to collect more drug consequence information in order to make subsequent patient (individual) based risk-benefit assessments. The group articulated some questions on this topic: Who will collect this data and who will be providing the financial and human resources required to support this activity? How will data quality be insured, and how will the signal to noise ratio be preserved (high)? Further, in recognition that health care providers can influence the risk to benefit consequences by virtue of how they 'use' the drug in individual patients, an additional question arose regarding the desire for implementation of controls on drug use in a post-marketing environment.
Recommendations -
It was felt that some of the enhanced information that is required to facilitate risk-benefit assessments with an individualized (patient) perspective should and could be obtained from patients (rather than relying on health care providers). In addition, it was felt that pharmacists might be the conduits for collecting this information, either directly during the prescription refill dispensing process, or by recruiting patients to participate in a patient follow up surveillance program.
Discussion Report #6
Topic : Criteria and Objectives for Framework
Initiator : Agni Shah
Participants : Two
Discussions, proposals, actions
- The mode should be more to "Help" the public rather than "support" the policies, procedures or processes.
- This would require a more proactive stance.
- An example can be: information available to HEALTH Canada (HC) should be used to inform the necessary stakeholders in their decision making.
- HC should seek cooperation from other authorities to get to the state required. Examples here include (a) justice system being approached for tighter enforcement (b) approaching Finance with data for increased funding.
- Teamwork is a great concept but team members must take responsibility for the overall outcome in addition to their own activities.
- Enforcement and consequences in terms of decision makers as well as perpetrators or agents. Example here is that a laboratory analyst can be penalized for analytical errors but the Supervisor who accepts an incorrect result is usually considered faultless. The manager who purchased and authorised use of outdated equipment may be congratulated for being under budget and the person setting up the budget is never involved!
- HC could be working to change other systems. Following a system is fine but correcting a system and getting the correct system is better.
Discussion Report #7
Topic : Communication
Initiator : Cathy Shea
Participants : Approx 35
Discussions, proposals, actions
Who is/should be involved?
Consumers, Physicians, Other health care providers (pharmacists, nurses, psychologists, social workers), Industry, Health Canada Staff (clinical trials, submission reviewers, policy, legal), Politicians, Provincial Ministries of Health, Canadian Institute of Health Research,
Issues:
- Should there be formal links between Health Canada and all involved groups?
- Should there be more links between the separate divisions within Health Canada?
- Links between Health Canada, CIHR ?
What is/should be communicated?
Pre clinical trial decisions, Clinical trial information, Submission information, Approval Decisions, Post-marketing information, Adverse Drug Reaction information, Peer reviewed "scientific" information, Physician to Physician information, patient to patient information, anecdotal information about effectiveness and safety, cost issues, access issues
Issues:
- Who owns the information?
- What are the limits of confidentiality? Should reviewers be allowed to comment or share information about an approved drug?
- Should there be a publicly available summary of reasons for approval?
- Should separate divisions within Health Canada be co-ordinating the flow by working together?
- Whose job is it to communicate/educate? What are the mechanisms for networking?
- Who will pay for communication/education?
- Should consumers have direct access to technical information? To "complete" information?
- What is the difference between education and marketing?
- What about "off-label" uses, orphan drugs, small patient population? How does industry tackle some of the "Catch 22" issues---- trials not approved for same reason trial is being proposed!
- Who interprets definitions or data around policies, technical detail, practical considerations?
When?
- pre-trial
- post approval
- post marketing
- safety issues
- when several drugs within the same class have yielded observations
Issues:
- Who will coordinate this?
- Who will update the information?
- How will we know if communication is effective? Has reached the right group(s)?
How to communicate/ educate?
- use available models such as public health models for communication
- use non physician health care providers to educate consumers
- greater links to International regulatory agencies to share information, perhaps joint reviews on some drugs?
Discussion Report #8
Topic : Key Values
Initiator : Françoise Baylis
Participants : approximately 10 participants
Discussions, proposals, actions
KEY VALUES
EXPLICIT VALUES
Safety
Efficacy
Effectiveness
Access
Accountability (transparency not mentioned till page 23 and again on 29)
Multi-stakeholder consultation
Who (should) determine the values?
Need for clear understanding/definition of these values
HIDDEN VALUES
- Keeping industry "on side" - wanting to make the system easier/better for industry (in places the text suggests that the modernized life-cycle system will serve everyone's interests (including the interests of industry), when in fact Health Canada should have a clear priority to meet Canadian interests, not the interests of "everyone" (See, for example, text of page 5 about Good Planning)
- Need to manage/mediate competing interests (profits, political accountability, public and bureaucracy). Why assume this? Why not give priority to the interests of Canadians and the interests of government in having a viable publicly-funded health care system.
- RCT as gold standard. This assumption gives rise to one of the ethics problems identified in the text - how to approach patients to participate in research for a drug available in the market place when this means they might not get access to the drug.
MISSING VALUES
- "Added value" with new drugs (regulatory framework should be attentive to this issue) If there is no anticipated added value, why undertake drug development ("me too" drugs). There should be a place for this value. Regulators should assess "need" Is the drug in development needed?
- Cost effectiveness - effectiveness is mentioned but it is not clear if this includes cost effectiveness
- Precautionary principle
CLARITY OF VALUES
- effectiveness is named as a value. What does this mean? What does this include? On page 16 there is mention of cost-effectiveness...
- safety and efficacy - presumably safety comes before efficacy - this is not always the ordering in the document
UNDERLYING ASSUMPTIONS that inform the document and need to be questioned (where is the empirical evidence in support of the underlying belief)
- Canadians value drugs to address health problems more so than other mechanisms
- Canadians want quicker access to drugs and are willing to trade safety for access.
- Drug development is and must remain a market driven activity
- Canadians can and will access publicly available information (via internet) about safety
- Proposed mechanism will increase access (it might actually limit access)
FRAMEWORK
- Need for sound clinical trials with appropriate inclusion criteria so that information gathering about diverse patient populations is not left to post-market surveillance. The proposed framework preserves (and perhaps entrenches) some of the status quo that ought to be called into question. One example: The proposed life-cycle approach includes much needed post-marketing surveillance and data collection, but there is tolerance for the current system which allows drugs to be approved and marketed without having been properly tested for safety and efficacy on the populations likely to use the drug. In a way this speaks to tolerance for current system of off-label use instead of seeking to minimize some of this. See for example, page 15 where an example is given of the need to follow up on children and the elderly in anticipation that data on these populations would not be available from clinical trials. Instead, the clinical trials should be more comprehensive from the outset.
- If there is a real commitment to the life-cycle approach, then there is a need to think outside of the current framework - reasonable to ask questions about more than safety and efficacy at the initial stages because Canadians want more than safe and efficacious drugs - e.g., they want cost-effective drugs, so ask questions about "need" "added value"
- How will the proposed system accommodate the likely assumption made by Canadians that an approved drug is a safe drug - this is a very real problem for the proposed new regulatory framework
- Need for more scrutiny of pre- and post- marketing
- Current proposal calls for an economic impact assessment, but what about an ethics impact assessment. Ethical issues are identified, but not engaged with.
- More attention to issues of informed consent is needed - what will patients, consumers know or believe about the safety of drugs under the proposed system where drugs might be approved with incomplete data.
- Problem of regulatory silos
Discussion Report #9
Topic : Process & Accountability (r.e. changes affecting pre-market process perhaps leading to earlier access).
Initiator : Anthony Ridgway
Participants : Ron Bouchard, Gilbert Matte, Michael Paterson, Alison Vanlerberghe, Mary-Anne Kent, David Kohoko, Robyn Lim, Sari Tudiver
Discussions, proposals, actions
Discussions around:
- the "evidence" upon which recommendations/decisions are, or could be, made;
- "hard" scientific data (Q/S/E & benefit/risk) by HC evaluators;
- "exceptional drivers/evidence" of benefit/risk by panels (or fed back to evaluators?);
- the process currently used and what processes could be introduced;
- preservation/distinction of standard Q/S/E evaluation;
- how/when to consider "exceptional drivers";
- how/when involve panels?;
- accountability and "sign-off" r.e. exceptional drivers;
- who signs-off what?;
- delegation by whom for what.
Proposals, actions, thoughts:
Don't want to erode standard upon which Q/S/E reviewer makes recommendation. If other factors are used to influence earlier market availability, standard review decision must be captured. "Exceptional drivers" need to be layered. Need clear processes, transparency r.e. interactions, delegation and accountability.
Could use one panel early to consider suitability of use/application of "exceptional drivers" (but how would this feed into the Q/S/E reviewer evaluation [or would it]?). Could use another panel, after completion of standard review, to feed into final HC recommendation (which may be different than recommendation provided by the reviewer).
How will those involved in current process (and their recommendations) feed into panels? Will panels feed back into reviewer process and, if so, how? Reviewer should not change their data-based recommendation. Need other layers of decision-making and accountability. How does this fit with the current F & D Act and Regulations and the requirements/accountability of the Minister of Health (and/or those to whom the Minister has delegated authority)?
Current approach (review of Q/S/E) incorporates benefit/risk assessments affecting number/breadth of clinical indications, product labelling, etc. For transparency in discussion and communication, need examples of the benefit/risk considerations arising through "exceptional drivers" and how they can be layered to arrive at a final decision. How do possibilities and opportunities arising from early access for those in need translate into benefit/risk evaluations and therefore feed into a final benefit/risk analysis influencing that early access?
Need case studies (in depth) to examine how/where problems happened in past as examples of how new Progressive Licensing approaches might have been beneficial. (e.g. early access proved beneficial and supportable [certain drugs for HIV ?] versus drugs having to be withdrawn from the market).
Be aware that small, vocal, pressure groups sometimes get disproportionate attention. Therefore, must keep standard Q/S/E review as baseline.
Need application of "system analyses" to the Progressive Licensing approaches.
Inspectorate relies on evidentiary standards for post-market activities. New types of standards may need to be developed for application to new products allowed on the market earlier via mechanisms resulting from Progressive Licensing.
Discussion Report #10
Topic : Non-industry Funding for Patient Advocacy
Initiator : Colleen Fuller, PharmaWatch
Participants : 10-12 people
Discussions, proposals, actions
There was general agreement that advocacy serves both the interests of patients and the broader "public interest" in Canada and should be funded - but by whom is the question.
Industry funding can raise conflict of interest within advocacy groups, a situation that is often recognised and discussed among advocacy groups across Canada. It can cause inner turmoil and tensions within groups.
Industry funding is also provided for development of clinical practice guidelines published by groups without disclosure of conflict of interest. This may be a problem in terms of credibility and also in relation to patients' interests.
Some people felt that public funding should be allocated to consumer/patient advocacy groups, but there are also questions about whether groups have a responsibility to raise funds from their own communities, from other private sector organisations and/or from members. However, some groups have to undertake fundraising activities at the expense of advocacy for the people they represent - public funding would ease these pressures on groups.
Pharmaceutical funding allows groups to be independent of government. Many groups were founded years ago when the question of what might compromise their integrity were dealt with differently. In the 1950s, for example, groups needed to distance themselves from government, not the drug industry. Today the industry is often more powerful than governments, so the situation has changed.
Industry funding enables groups to undertake activities that governments may not be able to fund; for example, industry funding has enabled research in adverse side effects of drugs to treat HIV/AIDs.
Groups should "draw the line" in relation to positions or activities that might represent a conflict of interest because of industry funding. This is a major topic of discussion among industry funded groups.
There were questions about how efficient it is for government to fund many groups all advocating similar things. Diverse funding sources (pharmaceutical, non-pharmaceutical industrial funding, membership funding, government funding) could play a role in encouraging groups to pool their resources (both financial and human).
Another aspect of public funding is around accountability. Advocacy should benefit the broader public interest, and funding could be used to create greater accountability and transparency among groups.
Public funding might also enable advocacy groups to engage more effectively with the industry as advocates rather than as funded (by industry) groups.
Many groups engage with Health Canada in a constructive fashion and if they aren't funded by industry this level of engagement is made possible with funding from Health Canada.
Industry doesn't want the public to believe Health Canada is in the back pockets of government, and they don't want government or the public to feel advocacy groups are either.
Industry funds advocacy groups as a service and to make them more aware of new products. Information is needed by patients about new drugs and Rx&D is guided by the industry's "ethical code".
Groups which receive industry funding often advocate for new drugs - and lobby provincial governments to fund those drugs. However, it never occurs to the advocacy groups to lobby the manufacturers to lower the prices of their drugs to make it easier for government to fund them with taxpayer dollars. This lowers the credibility of the advocacy groups.
Industry funding of the groups aims to create more equitable access to drugs across Canada. If drugs aren't in a public formulary, the may be unaffordable to patients. Advocacy groups are focused on that question when they lobby provincial governments to fund drugs.
Government funding can also cause problems, for example, funds often come with strings attached and when the funding ceases there are lots of problems!
Recommendations
To avoid the perception of conflict of interest, and to increase patient confidence, clinical practice guidelines should meet federally-established standards.
Individuals involved in developing guidelines should be required to declare any conflict of interest and such declarations should be publicly available.
Cost-recovery might be a way to enable Health Canada to fund things like advocacy and specifics such as clinical practice guidelines, ADR education/public awareness.
Increased taxes on the industry to support this type of funding? Good luck!
Health Canada might consider diverse funding to groups playing an advocacy role on behalf of patients/consumers. Health Canada should also consider its own role as an advocate for the public interest.
Health Canada should play a larger leadership role in disseminating information to medical profession and the public about issues important to patients.
Actions
Health Canada should consider these recommendations.
Discussion Report #11
Topic : Equality of Access
Initiator : Agni Shah
Participants
Discussions, proposals, actions
This was designed to talk about things we are not talking about or I have not heard people talk. Using Equality of Access as an example, it was hoped to discuss a number of other issues.
We need to define equality as well as access.. Is access availability or availability at a specific cost? Is it about timeliness? Is it about the time for response or quality of life? What about need and population details?
With reference to equality, do we even need it? Is it fair? When you provide something to one individual you are in fact depriving someone else the same or alternate thing because you are using the scarce resource.
There does not appear to be a mechanism to debate this and other similar issues. There are no guidelines and there is even fear to raise the issues. Consider the various scenarios and decide whether they are all equal and should have the same response. There may be costs and resources involved but there should be an open debate. Even if lawyers get involved, hopefully some of the resource and expense will come back in the form of taxes.
- A new arrival who has never contributed to the system
- An individual with funds, resources and loyalties elsewhere
- An individual who has not followed advice or directions
- An individual who courts the condition
- A dependent of someone who does not qualify
- Is a citizen, an immigrant, a visitor or deportee the same?
- Someone who refuses to carry out own responsibilities
This does not refer only to funds. How do we decide to apportion scarce resources? If only 3 can be accommodated and 6 require service, what do we do? How do we challenge the process? How open is the process? How do we monitor and resolve this?
Discussion Report #12
Topic : Issues, interests, & priorities regarding a new veterinary drug framework
Initiator : Jean Szkotnicki
Participants : Arezoo Matin, Monica Dhir, Randy Duhame, Franko Di Salvio, Jean Szkotnicki
Discussions, proposals, actions
Values
- Pets are an integral part of many Canadian households.
- Food animal production is critical to Canada's economy & rural fabric
- There is a link between human well - being & animal ownership e.g. human animal bond.
Issues
- Veterinary medicine is similar to human medicine but there are also differences i.e. there is no social financial support for animal drugs. This fact changes some discussions relative to areas such as importation and use of APIs, use of drug by food animal producers & DTCA.
- The Canadian veterinary drug review process lags behind the E.U., U.S., and Australia. Canadian veterinarians and animal owners do not have access to the same health management tools as those in other countries. This negatively impacts animal health, generally, and the competitiveness of livestock and poultry production.
- Investment in new animal health products in Canada has been negatively impacted by regulatory delays and lack of predictability. This also compromises availability of drugs in the marketplace and extension of label claims.
- The life-cycle approach for veterinary drugs will have limited benefit for veterinary drugs unless Canada takes measures to harmonize its policies on use of APIs and own use importation for animals with the U.S. & E.U. These products have not been required to go through any pre-marketing evaluation and there is no post-marketing effort. There are cases where these products supplant the sale and use of licensed Canadian animal drugs.
- Canada needs to streamline its veterinary review process such that a proportional review is conducted based on a product risk. For instance, a companion animal drug approved by FDA could undergo an expedited review process without compromising animal or human safety. One year of use in the U.S. is ten years Canadian experience.
Discussion Report #13
Topic : Ethical components of early access.
Initiator : Christine Nestruck
Participants
Bob Nakagawa
Ian Mackay
Milan Patel
Pier-Georgio Fontana
Muna Idris
Francoise Bayliss
Arezoo Matin
Kristin Loney
Brandi Epstein
Discussions, proposals, actions
- Early access is considered to be access to drugs before pivotal phase III trials are completed with full clinical benefit implications - the validity of surrogate markers remains to be determined.
- Is early access ethical ?
- Are we as a society prepared to give up options in terms of future research to generate knowledge? Clarity and verification of what Canadian patients want in terms of 'early' access.
- If approval under PLF comes at end of phase II, can one ethically conduct phase III with placebo?
- Patient responsibility for accepting entry into a clinical trial versus the informed risk process.
- Individual patient access versus need for robust trial protocols; only trials that are scientifically valid are ethical.
- Will innovative trial designs, i.e., adaptive designs, n=1 , address some of the ethical issues to allow better predictability of clinical values; fewer patients exposed to drugs ... more patient exposure at optimal.
- What is "promising"? particularly in view of well known attrition rates.
- To what extent do surrogate endpoints need to be fully validated in terms of clinical value and use to regulators in making regulatory decisions.
- To what degree do we compromise safety for early access?
- Mainstream drugs versus special situations.
- Define compassion: empathy versus sympathy.
Discussion Report #14
Topic : Does increased Postmarket surveillance activity justify a decrease in pre-market requirements
Initiator : Bruce Wozny
Participants : Deborah Wild OPI; Durhane Wong-Rieger, CORD; Alison Maloney, CAPRA; Michael Taylor, NHPD; Mary-Anne Kent, HC; Gasan Askerow, CMAAC; Mario Simard, Legal; Karen Timmerman, BGTD; Alison Vanderberghe, BioteCanada
Discussions, proposals, actions
Depends on effectiveness and purpose of tools
Identification of risks is one outcome
Which products should be subject to new pmv tools - all? Certain categories? or by exception?
PmV tools can be initiated, used, then modified over time with experience
Compliance and Enforcement
- how flexible should be be?
Priority review a model (i.e. same requirements, queuing priority)
SAP model (i.e. patient-specific only)
NOC/c (patient registry)
- increased PSUR periodicity
- qualified prescribers only
- increased transparency (patient registry results published)
- balance increased patient access to information with education to deal with possible issues like patient non-compliance, misinformation, faulty scientific reasoning
- HC access in real time to company database
Cost of measures needs to be considered
Do we allow flexibility around safety requirements, or just effectiveness?
Measures cold identify patient populations with special risk profiles
Accessability vs. burden of proof
Must harmonize with other countries on best practices basis
- e.g. risk management plan
- Canada has a limited population
Compliance and enforcement options other than market withdrawal are needed (e.g. financial penalties, communication of risks
MedEffect is a good tool
Is product-dependent; could it be product-class dependent?
Competition issues
- impact of "grandfathering"
- first-on-market/subsequent entry
- need to guard against skewing competition
Need to make sure we are harmonized internationally
Registries could become the norm for some products, e.g. biologics
- patients could enter their own data
- biologics could become the lead for these tools
Education needed to mitigate against misinformation
- CIHR, NIH, Mfrs?
Discussion Report #15
Topic : Is/ will the drug review process (be) managed in a cost effective manner?
Initiator : D. Kohoko
Participants :
Discussions, proposals, actions
- HC has focused on the requirements of the FDA which requires that a drug be reviewed for safety, efficacy and quality. However an important driver has always been the cost of the review. This driver is neither mentioned in regulation nor often considered from a policy standpoint. As we move forward into a PL framework, we seem to have maintained our focus on SQE. The concept paper does not mention, nor has any of the background material focused on cost issues, which continues to drive the review process.
- HC is doing the same review work as other jurisdictions only with much fewer resources. Other regulators are cost recovering or are funded at levels which promote better review times.
- Role of cost as it relates to the traditional balance of safety versus access.
- Fewer resources means delays in approval times.
- Are there system efficiencies that can be found to reduce approval times? For example, joint reviews with other international and domestic jurisdictions.
- Sharing data sets to get data faster
- More targeted therapies
- Tie standards to pricing of drugs on the market place. The time it takes to do a review or the price that HC charges for the service it provides should be related to the cost of the drug once it comes to market. Therefore high cost drugs which are more expensive to review than other health products, and the fee charged for those reviews will be higher.
- Partnering with international peers to reduce overlap and cost, and which will create efficiencies and better data sets. Working in parallel (doing our own work in conjunction with other agencies) and borrowing data sets.
- Progressive pricing - relating pricing to required conditions in the marketplace.
- Seeking out and taking advantage of existing efficiencies.
- Aligning the QSE review standards with evidentiary standards for public reimbursement.
- Finding a way to increase efficiency and data by combining the review process of various regulatory agencies.
- Cost Recovery - Creates benefits for government and for industry. Creates a safer environment and a better review process.
- Question: Is the a triage process for drug review? How does the reviewer determine which reviews to prioritize when there are multiple submissions to deal with.
- Provincial contribution for getting post-marketing data collection. Provinces, in many cases, have much more complete data collection and are able to access data sets quicker than HC can.
- Creating a forum to share / improve data sets.
- 100% cost recovery of 3rd party assessed cost review. This means that a 3rd party will assess the cost for HC to do a review and that HC charges for the full costs of a review. Canada is far behind other jurisdictions in terms of how much we charge for a review.
- Financial incentive or punitive measures for compliance / non-compliance.
- Predictability of the review process for industry. It would be nice to know the time and cost of a review prior to engaging in the process.
Discussion Report #16
Topic : Feedback Mechanism for consumers / Prescribers / Dispensers
Initiator : K.P.S. Aujlay
Participants : 7 participants
Discussions, proposals, actions
There must be direct and active reporting mechanism to and from Health Canada
Reporting mechanism should be user friendly keeping in view cultural sensitivity and language
Should be accessible to Prescribers and other members of the health care team
Enhance the role of pharmacist and other health care professionals
Communication mechanisms for underserviced / vulnerable communities such as seniors, rural population, immigrants, children and first nations
Health Canada should provide active surveillance
Communication back to consumers/prescribers/dispensers
Advisory letter goes to some health care providers, other professional should also be on the mailing list
Health Canada has a role in consumer education
Keeping in view diversity, translation into other languages for key products
Tie in with natural health products regulations.
Discussion Report #17
Topic : DTCA and Advertising to Health Care Providers
Initiator : Madeline Boscoe ed@cwhn.ca
Participants : didn't keep it
Discussions, proposals, actions
Asked what are the possible impacts and implications on the proposal
Focus in not just "advertising" but includes promotion/marketing activities such as advertising in media, detailing, support for Continuing Medical Education, support of patient groups, "media relations"
The current state of regulation of both are very problematic and will influence care negatively
The life cycle approach is incompatible with DTCA and promotion to HCP. In a life cycle approach, less is know at the beginning [though this needs some consideration and review for criteria] while the marketing and promotional activities are focussed on new drugs
Eg Vioxx, Diane 35, "social anxiety" drugs. We aren't going to list the all the problems-they are elsewhere.. safety, cluttering up of care providers, iatrogenic effects, costs.
This issue is missing from the document.
Unless the issue is addressed the proposal is likely unworkable. Likely hood of other vioxx, diane 35 example
The marketing activity will essentially recruit Canadians into an unmanaged post marketing program or "non clinical trial clinical trial" without their consent.
It was note that the US is discussing a moratorium on DTCA for new drugs for 3-5 years.
Therefore:
Health Canada needs to include in this document plans to
- prohibit DTCA reminder ads, "serial" ads and regulate media 'leaking" from other countries by cable, satellite, print
- regulate promotion/marketing[including educational grants] to health care providers[ in partnership with professional regulatory authorities]; patient groups, and the media
The document needs a Knowledge management strategy to actually communicate what is know and what is not know about the drug, how or if it adds value, and the magnitude of that value compared to other interventions or doing nothing. Include professional CME
This will need a new budget and infrastructure:
- remove tax write off for promotional activities
- create higher fees to industry to this strategy
- engage universities and educators in the process
Require industry to provide information on clinical trials participants and numbers. This includes
Numbers, population descriptors ie gender, age, race, health status, other drugs/health conditions, country of the trial and recruitment strategies.
Discussion Report #18
Topic : What is meant by "safe"
Initiator : Mel Fruitman
Participants
Discussions, proposals, actions
Canadians have a tendency to think that anything that is available (goods or services) are "safe", i.e. that some agency has ensured that they will not be harmed by using it.
They tend to make their decisions and actions based on that assumption. Their expectations are quite high if someone else is responsible for their safety rather than themselves.
"Safe" is not an absolute. In most cases it is really a measure of safety vs risk. Both patients and health care practitioners need to understand the equation.
Market authorization is a requirement and needs to incorporate the elements of; reporting of adverse reactions, labelling, product monographs.
There are gaps in communication with the public. Progressive licensing will lead to more understanding.
Safety has to do with context - how capable are we of monitoring changes in the market and catching any mistakes.
Need to get patients/Canadians engaged in getting information in pot-market.
What is public perception of the role of Health Canada? Confusion may be created because of its multiple tasks. With respect to food we expect that "safe" is indeed an absolute. The perception is that if it is available to be eaten, no harm will befall us, period. This even applies to food eaten away from home. (we do not think much about jurisdiction).
Given that that is not going to change it is necessary to change the language with respect to pharmaceuticals, etc. The public needs to be educated that what HC really does is a risk/benefit analysis. This is an entirely new concept for consumers and they will need to have it explained and be educated as to how it applies, generally and specifically. Since the population is not homogeneous, the risk/benefit equation for a given circumstance will give different results different for different groups of people.
There is also a question of trust. As the system changes to progressive licensing, consumers need to understand its benefits and not feel that HC has abrogated its responsibility to them.
Discussion Report #19
Topic : PRECAUTIONARY PRINCIPLE VS RISK MANAGEMENT
Initiator : Pierre Morin
Participants : from 5 to 19 participanrs
Discussions, proposals, actions
Discussions:
At the outset, every participant was asked to give his or her perception of the Precautionary Principle. We got as many answers as there were people but then accepted the definition retained by the Government of Canada, i.e. "Where there is a reasonable risk of serious or irreversible harm, the absence of full scientific evidence is no reason not to act".
Initiator added his concern that policy also states that the Precautionary Principle should not be a substitute to a risk management policy.
Participants then discussed when the principle should be invoked and where it should not be used as an excuse for not wanting to give real reasons for the decision taken, to the extent that the use of the P.P. may be perceived as the absence of a risk management policy.
However, in the context of progressive licensing where much greater emphasis will be given to the post market life of a product, the regulatory framework retained will have to define its risk management policy by the development of adequate tools for data collection and where it will need to integrate the P.P.
Recommendations:
Clear thinking will be imperative around the definitions of Risk Management and the Precautionary Principle in light of the implementation of Progressive Licensing
Discussion Report #20
Topic : Notice of Compliance - what is the bar?
Initiator : Madeline Boscoe
Participants : didn't keep list
Discussions, proposals, actions
In a progressive licensing regime, what is the bar for approval?
What are the assumptions?
Recommendations and discussion points
- It should not be implied that less is being done in the "pre market" approval stage or that less money is spent in Phase 1-3.
- andomized clinical trials and research registries are very important part of evidence --- how is this possible if drugs are on the market? What are we saying to patients?
- What will be the incentive for the manufacturers to finish research?
- Who will be responsible for post marketing research, how will this be funded and monitored ethically and responsibly. Need to move this out of the responsibility of the manufacturers and into a more transparent and accountable process where there are no conflicts of interest [professional and economic]. Need to put in place a tax or fee system that would support an independent review process
- At a minimum, the same bar need to be in place-safety and efficacy --- in the populations that are most likely to use the drug or device or be exposed to the chemicals etc. There is some evidence to suggest the bar is not high enough and that our approach to clinical trials needs to be rethought.
- Different drugs and devices need different standards of evidence. The Clinical trial framework/plan is very important and should be developed with a team that includes sociologists, medical historians, gender and diversity analysts too.
- Example- drugs used to prevent illness or on healthy populations. e.g. contraception, vaccines, "cancer prevention' vs clinical trials for terminal conditions in last year of life.
- We challenged the assumption in the document that Canadian are willing to trade "access" for safety and that approval of a new drug can be equated with access as costs, distribution and questions of real world efficacy remain.
- Recommend that we take a population approach when defining pre-market approval and think differently about clinical trials-Ask who is likely going to be interested in or will be the target of this drug--- and make sure they are included. Women, children, seniors, those taking other drugs, visible "minorities" [who are not minorities in some contexts in Canada] should not be excluded as categories. Clinical trials need to be meaningful to all Canadians.
- challenged the concept of "evidence" being juxtaposed against "demand" and raised questions about how real and deep that "demand" was. What are the impacts of industry sponsored patient groups, how deep is this push and when
- touched briefly on the issue of standard for life style vs therapeutic--- discomfort about treating these differently except in the prioritizing the reviews
Discussion Report #21
Topic : Gender Based Analysis in drug regulation
Initiator : Madeline Bosce
Participants : Sari Tudiver
Discussions, proposals, actions
Health Canada's GBA policy (2000) requires the application of GBA as a matter of standard practice in all HC programs, policies, research and other initiatives.
Health Canada's definition of GBA considers sex [biological, genetic, metabolic] and gender [an analysis of the social context over the life course.] GBA includes analysis of diversity ie population health approach.
As well, HC has an existing guidelines on "The inclusion of women in clinical trials"(1997).
There is currently no recognition of the need for GBA in the PLF concept paper and the next draft needs to include this. Emerging scientific understandings of sex impacts on physiology, sex linked expression, disease pathways and drug metabolism etc, demonstrate a need to have GBA as a foundation in planning and decision making.
As well, GBA needs to be considered in all aspects of any life cycle approach to drug/product regulation.
Implications and requirements for a progressive licensing framework.
- Pre market approval
- Evidence based approach then requires adequate number of the population targeted for the drug/device, with sex desegregation and analysis; subgroup analysis. The clinical trial framework should include a GBA of the disease risk so that conditions where sex is risk factor ie autoimmune conditions or where sex and gender difference may manifest differently in the aetiology of disease are addressed eg cardiovascular conditions
- Post market
- Surveillance systems need to systematically collect data based on all the above.
- As well, when developing a surveillance system, Gender analysis of health service utilization patterns, patient/provider relationships [i.e. which influences who gets what], access to extended benefits plans, use of over the counter medications which can affect drug interactions etc need to be addressed.
Recommendation: That GBA be integrated into the Blue Print process, through mechanisms such as a special workshop with HC scientists and policy staff, experts in GBA, drug researchers, providers and community to review the draft documents for GBA implications and make recommendations for changes.
Recommendation: As there have not mechanisms to monitor implementation of the Guideline on Inclusion of Women In Clinical Trials to date, and as we approach its ten year, it would timely to do so in the context of the clinical trials review.
Recommendation: that as part of the Blue Print renewal, the intent of the Guideline On Inclusion Of Women In Clinical Trials should become a regulation.
Discussion Report #22
Topic : Life Cycle for Near or Post-Patented Medication
Initiator : Micheline Piquette-Miller
Participants : approx 6 participants from Health Canada, academia & consumer groups
Discussions, proposals, actions
Issue: Who is responsible for generating safety information once a drug has gone off patent? Should the originator (Brand) continue responsibility or should generic manufacturers also be responsible.
Background: For every drug there is a PATENT LIFESPAN (market exclusivity) as well as a MARKET LIFE CYCLE (as long as physicians are prescribing meds).
At the point of licence (NOC) there is generally 10 yrs of patent protection remaining. Majority of safety information will be generated during this time and the Brand company will be responsible for submitting pharmacovigilence and periodic updated safety reports.
However many rare ADR and chronic safety issues may only occur and be reported beyond the patent life cycle (ie QT). Moreover long term efficacy and outcomes for many types of drugs (ie cardiovascular, anti-obesity, antidiabetic, etc...) may take 10-20 years to generate.
Currently generic manufactures not required to file periodic safety update reports nor pharmacovigilence plans.
Key Questions: What risk:benefit information will be required for re-evaluating the licence, when will this be performed (1 yr, 5 yr, 10 yr, 20 yr), and who will be responsible for putting together the safety-efficacy, pharmacovigilence reports?
RECOMMENDATIONS
A) Who is Responsible?
- Every manufacturer (Brand & all generics) has obligations for postmarketing surveillance of their products. Periodic re-evaluation and submission of pharmacovigilence reports.
- Databases need to be compatible.
Issue: Many generic companies do not have the clinical resources and expertise.
B) Who pays?
Should be a shared responsibility among all manufacturers.
Payment Models to consider:
- Incentive Model. Additional patent protection is given to Brand manufacturers for filing pharmacovigilence reports and paperwork or clinical trials necessary for post-marketing licence re-evaluation.
- Shared-Responsibility Model. Everyone that makes the drug is responsible for funding safety reports and pharmacovigilence analysis. Studies are performed by an independent body. Funding is obtained from manufactures using a tax-structure model based on market share. Other frameworks for dividing up responsibilities (funding or tasks) are also available.
- Combined Model. A mixture of additional patent protection and tax-based funding is used for additional required studies. Case-by case. For example, an additional clinical trial may result in an additional 6 month market exclusivity, but long term (20 yr) safety reports & pharmacovigilence analysis funded by all manufacturers.
- Network Model. An international problem, therefore Canada and other countries pay an international body (ie. WHO) to monitor safety/ pharmacovigilence. Drug manufactures could pay into this according to a variety of different payment models.
COMPLICATION: ACCESS ASSUMPTION NOT POSSIBLE AT THIS TIME.
*** These models are dependent on the time of market exclusivity remaining when product gets to market. (acceptability and complication of presented models will be affected if clock starts at different times for different products).
- PLF results in Early Access
:
Increased time of market exclusivity covers costs of additional post marketing surveillance. - PLF does not result in Early Access
:
Increased requirements imposes additional financial burden. Incentives need to be built into this system.
Numerous factors such as provincial formularies affects the feasibility of early access. Not all drugs will be eligible for early access.
C) Who packages the Pharmacovigilence/ safety information?
- Independent bodies
- Pharmacovigilence departments of Brand manufacturer
- potential for conflict of interest.
- WHO/ International - WHO standards are currently followed by everyone.
* Does Canada even have enough resources (trained individuals, funds, infrastructure) to perform all required analysis?
Other Factors that must be considered:
- How many additional post-market studies are needed, what are the costs associated and at what time point will be they be required?
- How much additional information is needed to make appropriate RISK:BENEFIT assessments? - there are increment benefits in outcomes with additional data.
- Changes in patent protection has international implications. Need some degree of international harmonization of IP. Not all data deserves increased patent protection.
- What are the behaviour drivers to encourage.
Discussion Report #23
Topic : Key Issues in Current Health Canada Regulations Affecting Access to New Medications
Initiator : Giorgio Fontana
Participants : Giorgio Fontana, Christine Nestruck, Randy Duhaime, Alison Maloney, Jackie Manthorne, Michael Hunt, Ian MacKay
Discussions, proposals, actions
The discussion started by agreeing to a common definition of "access". It was agreed that access meant receiving the best medications at affordable costs.
Access was discussed. In general the following points were raised:
- Canadians now have a much better awareness of what medications/treatments/therapies are available outside of Canada resulting in increased pressure for access.
- In Canada there is a geographic limitation to access (e.g. rural communities, aboriginals)
- The general impression of Canadians is that Canada does not have the same level of access as other countries.
Government funding and pricing in relation to product access was discussed. Points raised around this included:
- CDR/Provincial formularies must considered lives lost due to delays in funding.
- A system for Canadian wide funding should be considered vs. the current model of federal and provincial funding decisions. Individual provincial decisions were felt to be an extra, unnecessary step in a reimbursement decision. If the health economics data for a product is acceptable then this medication should be funded across Canada. Finally, it was felt that there is a need to nationally prioritize what drugs should be funded.
- What is the role of CDR?
- Information sharing between CDR and other countries should occur to facilitate/accelerate access to medicines.
- Progressive licensing may be able to "improve" access (in regards to reimbursement decisions) by taking better control of the lifecycle of drugs.
- The reality of a manufacturer's global business model must be taken into account when discussing access and pricing. If the cost of additional clinical trials is to high, the price set by PMPRB in Canada is too low, or if the product does not receive reimbursement, products may not be available on the Canadian market.
- Do price controls by PMPRB help market access?
Real life effectiveness data was considered and it was stated that if progressive licensing was adopted that specific, binding regulations need to be developed to ensure such data was studied.
Specific methods for early approval, which are used today, were looked at. These include:
- NOC/c
- Weaknesses do exist with this procedure. For example there are no binding regulations to ensure that conditions are met besides removing a product from market.
- Lessons learned should be discussed and studied to ensure that progressive licensing addresses any of these issues.
- If progressive licensing included conditions (as per NOC/c) what happens if the conditions are longer then the patent life of that product? How would one ensure that these conditions were met and who would pay for their completion if a generic company began to market this product.
- SAP
- Clinical Trials
- Progressive licensing could "open up" clinical trials by removing many restrictions (e.g. extensive exclusion criteria) resulting in more real-world trials.
Additional general points included:
- It was agreed that risk/benefit should be considered to determine if a product should go through the progressive licensing process. For instance, for those approvals focused on surrogate markers or biomarkers, more research may be needed for a better prediction of clinical benefit.
- Information sharing between Health Canada and other countries should occur to facilitate/accelerate access to medicines.
Discussion Report #24
Topic : Increasing the Quality and Quantity of ADR Reporting
Initiator : Patrick Cupido
Participants : Mitch Levine, Millicent Toombs, Kellie LeDrew, Paul R. Saunders, Monica Dhir, Karen Timmerman, Kim Dix, Bruce Wozny, John Service, Mike Ward, Joanne Butler, Sylvie Cantin, Mario Simard, Marc Berthiaume
Discussions, proposals, actions
Manufacturer has only mandatory obligation to report - passive
Physicians not required to report
Health Canada - passive receptive process
Need more prospective approach
Signal to noise ratio - danger of reporting everything
Where to set threshold for "serious"
Most of us will be on medication when we die - system will be overwhelmed if all are reported as potential ADR
Distinction between signal and noise is critical - key is pulling out valid info
Not necessary to establish causality prior to reporting - will be determined statistically
MedEffect - still can't submit report online
Doctors not reimbursed for reporting
Triaging of what to report
Misunderstanding of value of ADR reporting - early trend identification - don't need to get all - significant, unexpected or no other real explanation
If not enough info when initially marketed - value in greater reporting
Lessons from other systems eg. 911
Hybrid - spontaneous reporting plus systematically contacting people at intervals
Concern about mandatory reporting using current method (form) which is inefficient
Pharmacists currently largest reporters yet are not in favour of mandatory reporting
Mandatory reporting has not been found to improve system in other countries
We don't have enough health care providers - their focus is first on dealing with individual patient - what is the threshold for reporting
Different strategies needed for different groups - physicians, consumers, etc.
Consumer reporting does contribute to quality of reporting eg CTAC found that consumers were very willing to report ADRs face to face in community-based setting and that information was of good quality
Should we be addressing impact on quality of life rather than narrowly focussing on clinical manifestations?
Value of sentinel groups - either providers or consumers, new drugs or new indications
Workers compensation system - shields employers from legal action and employees get compensation and care - can something similar work for ADRs? - perhaps for medication errors, but issue of determining causality for ADRs - if could report without liability then they would be more willing
Consumers currently have no recourse other than the courts
People filling out the forms need to be asked how they should be designed - perhaps a short and long version
Off label uses - require sentinel system
Public education is needed - what is ADR, what is Health Canada doing Issues of trust among consumers
Reporting needs to become expectation of standard of care - integrate into medical education
Canadian College of Naturopathic Medicine has integrated into curriculum in cooperation with Health Canada
Role of pharmacists is key - everyone getting a prescription med is getting it via a pharmacist
Problem with consumer reports - if don't specify start date of all meds, difficult to determine causality
There needs to be a menu of reporting mechanisms available
Privacy legislation a barrier to consumer reporting via community-based organizations - is there a way around it?
What will motivate reporting?
Appreciation for importance of ADR reporting has not yet developed among providers/consumers
Australia - ¾ of reports from health care providers - they get feedback - if physicians could see feedback from their reports - practical value of reporting - currently a black box
There is a value to the system
Problem of interpretation - if ADR is an expected condition in disease or in sub population (eg. heart attacks in elderly)
Will still need other tools to monitor drugs post market
More info needed - ADR reports trigger studies - this should be made known as it would create incentive to report
Health Canada is working on info package for consumers
Community health clinic as a venue for info to and reporting by consumers
Health care provider - filter role - eg. not much value from reporting well established ADRs
Should enhancement of ADR reporting be focussed on new drugs and new indications?
Expectations of what ADR reporting can do must be realistic
Discussion Report #25
Topic : Regulation of orphan drugs for rare diseases under progressive licensing
Initiator : Alison Vanlerberghe (BIOTECanada)
Participants : Glenn Monteith (AHW), Maurica Maher (HC), Etienne Ouimette (HC), Mana Idris (HC), Susan Paetkau (Ontario Ministry of Health and Long Term Care), Bob Nakagawa, Durhane Wong-Rieger
Discussions, proposals, actions
- seem to be approved and considered for reimbursement under exceptional process
- products for rare diseases are being reimbursed under SAP, which seems to avoid review and NOC process
- SAP is the catch-all, which is a concern since the manufacturer will avoid the review, labelling, quality and GMP aspects to marketing the product
- responsibility for bringing the product into Cda under SAP lies with the physician. HC has no authority beyond the initial approval to import the product on a patient by patient basis.
- SAP must have a minimum requirement
- disconnect between knowledge of patients on SAP medication prior to NOC. Provinces are often surprised to hear that patient is receiving product, and then expected to pay at NOC.
- for products with an NOC, drugs are being used off-label for orphan indications
- government should consider sponsoring studies to examine the efficacy in these indications
- HC should consider requiring manufacturer's to formally study these indications
- government is considering policies that will promote industrial development in orphan diseases
- Orphan drug policies have proven to be very effective in promoting the development of drugs address unmet medical needs in these very small populations
- will the price tag for these medications be too high to pay by the provinces?
- Health Canada cannot remain passive with their decisions to approve these medications, since the implication downstream for the payers is significant
- Need to recognize that there are currently different standards of evidence for approval vs reimbursement
- could progressive licencing model address the disconnect between the evidence required for approval, price and reimbursement. Could a direct correlation be built between early approval and introductory pricing and reimbursement? This relationship could change as more evidence is provided through the lifecycle of the product. This is not currently possible with the PMPRB guidelines, although there is discussion ongoing with rebenching of pricing.
- need to continue to build alliances/partnerships with other jurisdictions to understand the international environment and best practises, both with approval of these products and subsequent reimbursement
- need to consider post-market programs or registries that are independent of companies
- need to look back at our experiences to date, to better understand how to build these programs
- programs are not effective if there are examining a host of endpoints, and work best if they look at well defined and few endpoints
- need registries that don't simply collect data but may test hypothesis
- registries are not designed to replace RCTs, but may provide data for further study
- registries can help drive the standard of care, and will have the ability to drive changes in how patients are treated beyond the labelling of the drug
- interest in sponsoring national disease registries that do not rely on use of proprietary databases
- there is the need within the progressive licencing framework to consider the place of surrogate endpoints vs clinical outcomes in the study of rare diseases
- we need to ensure that surrogate endpoints are appropriately validated
- are placebo-controlled studies required? These are ethical questions that need to be discussed.
- how will future innovations (i.e., gene therapies) be studied in these populations, in the case that a comparator is available
- what should be HC's role, beyond NOC?
- why are we in this position of having to discuss at some length how to regulate these drugs?
- should the approval of these drugs be linked to decision to pay for them?
- recommendation that HC should not depart from their mandate of assessing safety, quality and efficacy; however, needs to be a good way of sharing their review with the groups that assess these products for reimbursement.
- payers need to have a suitable level of evidence to make decision, but recognition that standards of evidence for rare diseases may be different that drugs for the broader population
- need to discuss implementation of policies that identify standard of evidence, appropriate study design (i.e., "n of 1 studies", for the study of rare disease. Guidelines need to consider the international standards as well as considering the Canadian situation.
- progressive licensing should recognize that drugs are approved as part of continuum of its development
- accept that there are unique challenges with these drugs, and that the approval and reimbursement system should be flexible to assess these drugs with the understanding that Canadians need access these medications
- at the same time with need to be fair and equitable in our decision making
- tighter rules may deny access
Discussion Report #26
Topic : Self Induced and Self assisted Illness - Needs of the Consumer
Initiator : Agni Shah
Participants : 2
Discussions, proposals, actions
This was an attempt to discuss whether "public" funds should be expended to mitigate situations where the patient contributed to their own woes. To some extent they brought on the situation themselves. Should there be any apportionment? What is the responsibility of the individual? Are or should there be limits to claims on public coffers? Simply put, should A,B,C... contribute to the resolution of issues caused by X to X?
Let us take some examples:
- An individual chooses to self-medicate or change medication for any reason.
- An individual persists in behaviour likely to harm him/her
- An individual chooses activities that have elements of risk
As a result, the individual makes a claim on the health service. Any resource expended is now not available to the rest of the community. Is this what we want? Should the individual take some of the responsibility? Should there be a debate about the issue? If someone else induces this action (e.g. advertising or testimonial) how much responsibility resides there?
Consider now that the resolution can be helped by non-drug intervention. Can Health Canada participate in this area? How can they collaborate or pass on the issue?
Health system is visualized as an Insurance scheme. This means that payments in are a form of premium and therefore all claims are admissible. Is this what we want? Is it insurance or a contributed benefit? If the latter, we can think of it differently.
A lot of discussion and thought has gone into the subject while discussing smoking, alcoholism and addictive behaviour and it is not proposed to rehash those discussions. It is also not desired to discuss freedom of choice or individualism in this context. The purpose is to point to some possibilities in terms of action and debate given and accepting that resources are limited.
There is always room for efficiencies in terms of expenses and that is also excluded from discussion here.
What may the consumers want?
- Consumers are interested in outcome and in process only in as far as outcomes are affected. And the outcome is total health as a part of complete lifestyle. Therefore difficulties and jurisdiction issues are not of concern to them. Who does what and how is of less importance than what is achieved.
- Consumers are the ultimate payers of the system and are therefore interested in the choices made by all deliverers of the outcomes. This requires that the decisions be open and transparent with all available information and limitations. Hence their interest in "How much of this do I have to pay"?
- Consumers would like it if all decisions and assumptions are open to review and debate in view of newer information. Nothing should be solved for ever! Nothing should be unchangeable.
- Consumers would like fairness and advantages not given to lobbies or special interests as that means depriving the rest of the community.
Discussion Report #27
Topic : Responsibilities and Information Flow
Initiator : Agni Shah
Participants :
Discussions, proposals, actions
This refers specifically to post market activities. Once information is available, the onus should be on the holder of information to adequately transmit it to relevant stakeholders. A process must be developed to assist in this endeavour. This presumes very good interaction, infrastructure and adequate resources. Lack of information is one thing but lack of knowledge of information or action as a follow up to the information are very different things.
We must determine and define:
- The starting point of the information
- Checking the information with timeline
- Dissemination of information
- Confirmation of receipt of information
- Action based on the information
- Limitations of the information and actions
Information is of no value if not with the parties that can act and that parties do act. It must be converted to "action".
We probably need thought on:
- What the physician will do when in possession of some information
- What any other health professional will do
- What a non-professional should do
- What Health Canada should do
- How this will flow to the patients / consumers and all intermediaries
- What about liabilities
We also need an assessment of the process.
Discussion Report #28
Topic : Consequences of Decisions - Collaboration
Initiator : Agni Shah
Participants :
Discussions, proposals, actions
When something goes wrong, there is a tendency to examine or determine why that happened and who or what was responsible for this state of affairs. How far back should we go and how can we both prevent and mitigate the situation? This is really a plea for root cause analysis and actions based on that or similar studies.
This is also to suggest that more and better outcome may be possible if a wider approach is taken. Say a drug has failed to perform as expected in the market. We may know this from post marketing surveillance or progressive licence follow ups.
We might consider:
- Was the drug correctly produced and used?
- If not, where did the process fail?
- If yes, should this have been anticipated in the review?
- Was the review inadequate or was sufficient information not available?
- Was there pressure on the reviewer?
- Were the earlier studies incorrect? If not, were the requirements inadequate? What can be changed?
On another level:
- Did anyone else contribute to the issue?
- How can that be improved?
- Can anyone else help the situation now?
- How can we get them to pitch in and collaborate/
- Who or what is responsible?
- What could we have done before and what can we do now?
Or consider:
- Is this a training issue?
- Is this a resource issue?
- How about publicising this so that others can learn from it?
- If information was wrong, how can we prevent a repeat?
- If decision was wrong, how can we avoid it?
Decision makers must be held responsible for their decisions. It is not enough to plead that there was only partial information. It is not enough to plead pressure or lack of resources.
Discussion Report #29
Topic : What Should Health Canada's Role(s) Be?
Initiator : Robyn Lim
Participants : Chera Jelley, Mel Fruitman, Ray Chepesiuk, Anthony Ridgeway, Marc Berthiaume, Pierre Morin Many-Anne Kent, Gilbert Matte, Kim Dix, Bruce Wozny
Discussions, proposals, actions
US labelling initiatives: industry driven; relates to/driven by legal responsibilities?
Observations: can't sue the US government
Roles hinge on the kind of product at issue: "context": e.g. when there is narrow indication, or benefit not clear: roles shift depending on context
Is it possible to classify products on risk? A: has been tried before and failed "Product Licensing"; can't necessarily know ahead of time what the risk is, benefit needs to be contextualised too. Although could classify after review complete.
Benefit-risk: if recognise this, then can see there is a trade-off for the potential user
Who is accountable? Answering this question would inform as to role(s)
When it is "crunch time": regulator needs to take over: this is a reality, although not necessarily for the right reasons
Role depends on the drug at issue (e.g. disinfectants): these have lower risk and therefore HC is a facilitator: some disagreement on the perceived risk issues with disinfectants
Responsibility: we need a more efficient healthcare system: dynamic, use all resources available in the system, user assumes responsibility for own well-being
Significant change in the system from one of HC having the primary role, to a shared responsibility of all participants
Agreement that there is shared responsibility, especially now, with patients calling for more autonomy
Diagram by one of the participants describing continuum of: a) restriction (safety?) to full access; b) safety with efficacy/benefit with risk; c) patient understanding (low to high); drugs can fall within individual sectors and the role of HC would depend on where the individual drug would fall; also incorporates lifecycle concept to learn continuously
HC has all the 3 roles: health protector, facilitator of access, information provider:
a) with respect to protector role (first step): in the context, determine the S/E/Q and B-R profile: b) if B-R is soft, we need to look at other factors -> then look at facilitator role, including risk management options (this includes the information provider role)
With Progressive Licensing: facilitator role will be more important since will have less info on product before goes to market: Question: do we want all products to go on market with less information: A: no: just particular ones in certain circumstances.
Distinction between benefit and effectiveness; benefit is more nebulous/big picture, with decision made by many people, where everyone will have a role
But assessment of efficacy/effectiveness/safety is the role of the regulator/more of a burden on the regulator; safety is almost an absolute
With respect to the 3 roles: a fundamental question for HC: what can HC do well? What parts can others do it better?
Observation: comments from participants seem to fit, in general, with the concepts described in the concept paper, i.e. regarding making for a clear distinction between the layers of evidence: 1) S/E/Q/, 2) B-R level 1 and 3) B-R level II; and regarding involvement of larger spectrum of decision-makers in cases where B-R level I is not clear: is this so? General agreement
e.g. 7th me too drug where manufacturer intends to offer product at half price of other drugs: what should be done here; general response for participants: this is outside HC's scope; comment that $ is political/not scientific
Another comment regarding what can HC do best? HC can't do it all by itself: use of other reviews/ decisions by other regulators (Australia, Norway, Switzerland). This participant supported following Australia's lead to approve based on others' approvals.
Comment: contextual issues for the country that may be different than in other countries; concept of drug review as a science, best served by multiple, independent assessments. HC currently does use foreign reviews; more information can help, but this is different than taking a decision based on another jurisdiction's decision.
Comment that using other regulator's decision is related to resources and expertise, and not part of the question at hand. General agreement
If benefit-risk profile is not ideal, HC could say 'we need more data", but if there is a clear patient need, HC may need to push into facilitator of access role
Suggestion that the reviewers embody HC's role. IOM report and its description of FDA reviewers' role mentioned in this context.
With respect to who takes the decision: why not use court model? i.e. where patients and others are involved in determining the issues (and where everyone has the same information at hand), with a single "judge" from the group to make the decision.
Comment that this is similar to the "body" described in the concept paper, but no details suggested there about who actually would make the decision. Could therefore be a decision by an external person.
Comment that the Minister currently delegates down, usually to Director General level, and that the DG generally relies on the reviewing division and manager regarding their recommendations: Responsibility therefore often comes down to the Division Managers who expose themselves to significant risks (examples of this already in the system)
Comments that we don't necessarily need a judicial approach, but as decisions are made on less data, we need a larger group to consider the issues, with careful documentation of their deliberations and rationales so that in the course of time, others can make judgements on these decisions in the context of the information available at the time to this larger group.
An example: 5% chance of death: what do you do? Can you identify the population at risk? What if the condition is not a life-threatening one? What is the benefit-risk? No clear answers to this one...
HC is also an auditor/enforcer e.g. with respect to risk communications: if HC decides risk communication is the legal responsibility of the manufacturer, HC's role is one of auditor/enforcer; duty of care is also a consideration. We have to be careful as to the roles we pick. Observation that the role of the regulator is slightly different than the same role by others: e.g. risk communication: if HC is responsible, the role is slightly different than if industry is responsible for this role.
Discussion Report #30
Topic : How can we improve ADR signal reporting?
Initiator : Levine
Participants : Combined with another group
Discussions, proposals, actions
There is a need for a menu of options to improve ADR signal generation, as no one system is sufficient, and the options are not mutually exclusive. ADR signals are valuable for generating hypothesis that will be subsequently evaluated using epidemiologic methodologies. On their own, ADR reports do not provide information regarding causality.
To be useful, the signal to noise ratio must be optimized, thus any attempt to increase ADR reporting needs to focus on: 1. Improving signal detection (not just volume, as that would increase noise as well) and 2. Ensuring high quality data in the reports.
Resources for enhancing ADR reporting should focus on new drugs (first 5 years) or drugs with new indications. That is not to dismiss the need for surveillance of older drugs, but is in recognition of the limited availability of resources and the need to be efficient in trying to modify and enhance the current system.
The recommended approaches to improving ADR reporting include:
- Spontaneous patient reporting of ADR. This is a relatively untapped resource. Patient education to encourage reporting needs to be done. Education will also need to include how to ensure that the reports are high quality so that Health Canada can use the information. Patient reporting ADR to patient support groups, societies and associations needs to be considered as a useful option, as patients may feel more comfortable reporting ADR to these groups rather than directly to Health Canada (the info would then be forwarded to Health Canada). Issues of information privacy will need to be addressed. Mechanism to inform and educate patients regarding their need to provide this information could be done through pharmacies, since all patients receiving a prescription medication do so through a pharmacy.
- Sentinel patient reporting of ADR. While face to face collecting of data may be very useful, this is very resource intense. An alternative would be to identify patients either taking a specific drug or with a specific disease and following them prospectively over time with intermittent telephone calls to assess for ADR. In addition, outcomes like quality of life etc. can be captured over the telephone using validated instruments. Recruitment of patients can be done through pharmacies (at the time of dispensing) or through voluntary enrolment by associations or patient support groups.
- Spontaneous physician reporting. There is a need to enhance reporting from this group but mandatory reporting will increase noise and obscure important signals. To enhance signal reporting, one suggested approach would be to do an intervention in the medical education programs across the country, during the MD degree program. Another approach would be to provide better feedback to physicians in the community who do report ADR, as this would reinforce continued participation in this role.
- Sentinel physician reporting of ADR. Identifying physicians willing to complete forms in a prospective manner targeting either specific drugs or patient groups. (This would be similar to the green card system in Britain.)
- Hospital pharmacist reporting of ADR. This has traditionally been a valuable resource for ADR reporting. This would continue to be a key resource for obtaining ADR reports involving serious outcomes (that lead to hospitalization).
Discussion Report #31
Topic : Framework for review/approval of Drugs/Vaccines where Human Efficacy Studies are not feasible
Initiator : Milan Patel
Participants : Joanne Butler, Anthony Ridgeway, Ian McKay, Michael Hunt, Christine Nestruck, Glenn Monteith, Chera Jetley, Colleen Fuller, Patrick Cupido
Discussions, proposals, actions
Extraordinary use products mainly for Bio- Chem- Defence or Bio- Chem- terrorism
Agreement that a mechanism needs to be placed within the regulatory framework for review and approval of products where human efficacy data is not available.
Decision needs to be made whether this mechanism should be a continuum of the Progressive Licensing Framework or whether it should be a separate mechanism. Review can go up to a certain point under the PLF system but then diverge into a special or extraordinary circumstance.
Suggestion that the product approval under this mechanism should not be an "NOC" but some sort of authorization under a different name to allow practitioners and patients to know that the drug has gone through a different review process compared to a normal drug
Patient consent even after approval should be required. This might become difficult in situations such as DND or under an emergency.
Compare the new framework with Interim Orders rules and determine whether the approval authority should be with the Minister of Health or higher? The framework should include provision for discretion on behalf of the minister
Determine security concerns. Some available data in the submission may compromise national security if it becomes public.
Allow for various levels of review beyond safety and efficacy. Review should include threat of bio- chem.- warfare. Risk/Benefit analysis should include the risk of threat.
Under the PLF, can allow for manufacturing and stockpile of these products.
A condition of approval needs to include a stringent and iron-clad requirement for reporting. This should be part of regulation.
Include provision for immediate start of a clinical trial process where controlled data can be gathered to generate knowledge. Remember that the drug can potentially cause adverse events beyond effect of the warfare agent.
HC leadership will be needed in reporting process. Provincial colleges can institute standards.
Animal models and surrogate markers will need to be considered on case-by-case basis. But regulations should ask for detailed and reasonable amount of work.
Accountability on behalf of the reviewer needs to be considered. Also consider the fact that a standard a reviewer used to standard submissions will be reviewing non-standard data.
Recommendation: Set up an expert advisory committee that includes public experts
3 levels.
- Current Knowledge,
- Knowledge that can Potentially be generated
- Field Experience
Consider standards used by CTA reviewers for first-time in man use.
Dosage will need to be considered and relevance to humans.
First approach should be to look at the products in a traditional way and determine gaps.
Discussion Report #32
Topic : Identifying Key Players, Roles and Responsibilities
Initiator : Monica Dhir
Participants : Kim Dix, Etienne Ouimette, Ken Potvin, Brandi Epstein
Discussions, proposals, actions
Issue: Pre-market- access to drugs in Canada and role of decision makers at F/P/T level and Common Drug Review (CDR)
- less role of private insurers
- what is the role of patient advocacy groups
- consumer's role? - dealing with misinformation - patients responsibilities to find the best information
- issues around NOC - limit decisions made at CDR level
- even with safety and effectiveness information, public drugs plans can not support to reimburse any drug because of budget (issues of funding) - affects access
- Health Canada continue to have a role to seek safety and efficacy of drugs as a condition of NOC
- Health Canada's role should not be one of pricing, rather role should be still about reviewing safety and efficacy of drugs for approval purposes, and in a progressive framework, about reviewing and acting on new safety and effectiveness information
- if drug is not as "effective" then drugs plans should be flexible or comprise - to ensure affordability and access. This should also extend to Health Canada in having the regulatory flexibility of amending or imposing conditions to the approval of a drug.
- Canada should have a role at the International level to apply pressure and drive prices down for drugs that have shown not to be as effective as anticipated when first approved by HC - business decision
- public awareness needed on how the system (objectives of approval process and CDR) works and who are the decision makers
- there should be a collaborative approach/network (at arms length) between the various decision makers, possibility of the creation of an agency.
- under Catastrophic Drug Coverage - variance among provinces ( e.g. Atlantic smaller portion)
- Federal govn't has a role to ensure equality - access - Canadians should not have to move to another province
- National issues - common or national approach may be required - involving all levels of govn't. This is especially true if Health Canada goes beyond its historic role of pre-market review to assessing and acting upon new safety and effectiveness information post-approval.
- the role of health providers should be to communicate to patient - about the drug's safety and effectiveness
- Education of patient and consumer on drug coverage plans etc - ensure Patient Autonomy
- Industry should be required to have a patient registry for new drugs for which the risk/benefit profile has not been fully established: how to implement and what would be motivation/incentives: for industry it would be early marketing and for health care providers, it may call for a compensation
- Provinces are not aware of whom in their provinces are being treated with drugs released through the Special Access Programme
- effects on reimbursement
- issue of sharing confidential information between govn'ts
Issue: Post-market and "progressive licensing" - roles and responsibilities
- Health Canada should be more active to reviewing and acting on new safety and effectiveness information even after the product has received marketing approval - what should be done with this data (decisions made by Health Canada) - recognize that may/will affect what is listed on formularies - should be national vs provincial approach under the Canada Health Act
- approval by Health Canada place a burden on provinces - under a progressive approach, if Health Canada is getting into the business of reviewing safety and effectiveness information, this is likely to add more pressures on provincial drug plans - this may call for a national approach to managing drug access as opposed to a provincially-based system
- there is value at looking at the life-cycle approach to products - "progressive" licensing under NOC - certain conditions should be based on populations ( i.e. cancer) - to ensure required data ( can be smaller studies, lesser requirements, use of International studies etc.)
- for new drugs - mandatory patient registry would assist in more data for future populations
Discussion Report #33
Topic : Transparency in Reporting Negative and Positive Results
Initiator : John Service, Canadian Psychological Association
Participants : Ron Bouchard, CIHR
Michael Peterson, Institute for Clinical Evaluative Sciences (ICES)
Kelly LeDrew. Canadian Psychiatric Association
Bruce Wozny, Marketed Health Products Directorate
Sari Tudiver, Bureau of Women's Health and Gender Analysis
Discussions, proposals, actions
- Transparency and Conflict of Interest: Important intersection of interests
- Levels of Transparency: Clinical trials data:
- Mandatory clinical trial reporting regardless of results required by regulators by the NOC.
- Need sufficient detail. Not sufficient enough at the present time. Health Canada (HC) encouraged to keep working towards more data disclosure (Canadian and international).
- Early phase data: confluence of commercial interests and the public interest
- Some jurisdictions have more data available, especially negative outcomes data (eg USA).
- WHO's 24 Benchmarks important progress.
- Encourage HC to continue to develop MOU's between international regulators re data sharing.
- Some clinical trials data from other jurisdictions do not meet Canadian scientific standards. This data should be used contextually and not as part of the primary data for decision.
- Patient Education: Canadians need to understand that every drug has side effects. There is no such thing as a completely safe drug. Rather than drugs being safe Canadians need to understand that drugs have relative risks and intended benefits rather than being safe which can connote no risk.
- Increase publication of negative scientific results by HC and scientific journals. Scientific publications in all disciplines and across the research spectrum (NSCERC, CIHR, SSHRC) concentrate on positive results only and this is a serious constriction of the advancement of science and public safety.
- Data exclusivity is different than patent protection and is the prevue of Industry Canada (IC) while HC is responsible for safety, efficacy and effectiveness. Recommend encouraging HC and IC to continue to explore ways of increasing cooperation and collaboration.
- As HC moves towards a "gatekeeper" role, what information is essential?
- Move toward full and complete disclosure of negative research results, both domestic and international
- More complete ADR reporting
- Manufacturers compelled to report all side effects and not just those that fall within the definitions of the Notice of Compliance (NOC).
- Are there ways of improving the data reporting relationships and effectiveness of reporting between providers and companies? How can HC ensure it receives all of the ADR data from manufacturers so as to reduce possible citizen and provider cynicism? How can HC and the manufacturers better motivate compliance with ADR reporting so those reporting are ensured that the information is being used? This is a communications issue.
- Encourage HC to continue their efforts to make use of internationally pooled data and to develop effective ways of mining the data or using mined data for the benefit of Canadians.
- CDRs are becoming more utilized which is positive. Increased involvement of stakeholders (eg clinicians, consumers) on CDR panels will improve their decisions and involving these stakeholders early in the process will be a benefit.
- Cost-effectiveness and access are becoming more important factors for regulators when considering their decisions. At some point clinical guidelines will influence regulatory decisions based on empirical evidence supporting non drug therapies when and where they are shown to be more effective or effectiveness is clearly improved with a combination of drug and non drug therapies. This relates directly to health outcomes, access and limited resources.
Discussion Report #34
Topic : An appropriate regulatory framework for established products for self care
Initiator : D.Skinner
Participants: 10 participants
Discussions, proposals, actions
Participants felt that the product life cycle in the progressive licensing document was incomplete as it did not relate well to the self care product class (OTC and NHP). Specifically the life cycle figure only accounted for products with their genesis as a new chemical entity or a new indication for established products but primarily the presented life cycle is prescription oriented. Further, the prescription drug life cycle needs to be amended to reflect what happens to an approved prescription drug once the post-market surveillance evaluation leads to continued marketing versus product removal.
What is missing from the framework is that the self care product life cycle follows largely different steps (some similarity). The framework as augmented by the accompanying self care product life cycle would give a more complete picture of what is needed. (See Attached jpeg).
The critical overlap between the prescription and self care categories may be the area for progressive licensing (Rx switch).
It was also recognized that, unlike Rx products, the graduated licensing for self care products takes place at the provincial level. Specifically, Health Canada licences products with conditions of use (claim, safety information, quality requirements, monograph/labelling) while the provinces schedule products according to conditions of sale (under a physician order, under a pharmacist control, under the supervision of a pharmacist or without conditions of sale). Prescription drugs are sold under the same conditions of sale uniformly by the provinces and those conditions are that the product meets the conditions of use approved by Health Canada. Self care products are scheduled according to the National Drugs Schedules (not completely harmonized but largely so). For example, new self care products are evaluated according to the cascading factors whereby the default for any new substance is prescription status. If the product does not meet the prescription factors it will fall to the pharmacist dispensed category (schedule 2) (Note that the federal and provincial factors for inclusion in schedule 1 and schedule F are the same.) If the product does not meet schedule 2 factors then is falls to schedule 3 and if it does not meet these factors then it is not scheduled at all.
Some issues affecting the access to new self care products include:
- Rx switch - the current gazetting process needs to be replaced with and administrative list to ensure that once a risk benefit decision is made to allow the switch that it happens without undue administrative delay.
- Better coordination between the Health Canada approvals and the provincial assessment to ensure improved harmonization of both conditions of use and conditions of sale.
- A consistent and singular approach to regulating all self care products (OTC and NHP) by moving self care products out of Part C of the regulations and into a separate and appropriate set of regulations commensurate with the relative risk profile of this class of products vis-à-vis prescription drugs.
There was agreement among the participants that the critical elements for an appropriate regulatory framework for self care products include:
- Post-market surveillance for safety
- Pre-market submission data on safety and efficacy
- GMP/quality assurance
- Adequate and consistent science applied through the standards of evidence.
The major element of the progressive licencing framework that was outside the scope of self care regulation was the need for systematic post-market evaluation of effectiveness. The major reason why this was felt to be unnecessary was the fact that there were two major uses for the data collected: cost benefit decision making by payers and removal of a product for failure to provide the therapeutic claim. As it relates to self care, the cost benefit analysis is done an individual basis by the patient (n=1). Provincial governments don't normally reimburse self care products so the drug plans would not make use of the effectiveness data. People who find the product ineffective for them (not all products work best for 100% of the population) will discontinue use and choose a new therapy that does work for them. With respect to using the data to remove a product for failure it is unlikely that such an action would not be necessary nor wanted. Products failing to provide a therapeutic benefit for a disease that would then progress to a more serious condition would be products for illnesses that are treated by prescription drugs. Self care products are indicated for conditions that are most often self-limiting and product failure will not result in a significant health risk (this is one of the factors for switching a product from Rx status).
Another consideration is the volume and clutter in the post market environment to have to increase the utility of post-market surveillance for safety of the 20,000 -40,000 self care products (In addition to Rx) and obtain effectiveness data.
Discussion Report #34
Map
Discussion Report #35
Topic : Role of Culture in approval process
Initiator : K.P.S. Aujly
Participants :
Discussions, proposals, actions
While Considering this topic several questions come to mind
- What is culture?
- What culture has to do with the approval process?
- How the approval process moves?
- How information is processed by different cultures? Etc.
There are no simple answers to the questions raised above. However the fact remains that Canadian population is very diverse and certain diseases are more prevalent in some cultural groups than the others.
Therefore, focus on cultural aspects of population during approval process could prove very productive and cost effective both to Health Canada as well as to the Manufacturers of Drugs.
- For example, if there are no participants from First Nation Population in Clinical Trials for drugs for Diabetes, then will the effectiveness of Drug be questionable?
- For example, Health Canada spends a lot of resources and time to develop information about Drugs. However if this information is not getting to 25% of Canadian Population or is being sent to them through medium that is not culturally sensitive and appropriate, Will it have the intended impact?
- For example if in the proposed Progressive Licensing there is no input from immigrants, socio-economic minorities, First Nation population, after marketing could the word Progressive in Progressive Licensing end up depleting its meaning.
Health Canada could and should use appropriate cultural strengths to make the approval process culturally sensitive, appropriate, timely and cost effective.
Discussion Report #36
Topic : Communicating information from the Drug Safety Monitoring System to Providers and the Public
Initiator : Millicent Toombs
Participants : 6 - 10
Discussions, proposals, actions
Recommendations:
- Health Canada should take an active role in informing the public directly of drug safety information in a timely and relevant fashion.
- Health Canada should establish a consumer drug information system as part of its Blueprint for Renewal.
Discussion
Getting Information to Providers
One of the challenges is getting the necessary information when it's relevant to you. Often health care providers get overloaded with warnings and many of them end up in the trash box.
Is there a way of providing information in a timely fashion to practitioners so that it's there when they need it, and so that the stuff they don't need is filtered out?
- E-prescribing systems might be able to help with this.
What are a warning's implications for clinical practice? HC might contact medical regulatory authorities or other bodies to discuss the clinical implications of their safety advisories; but colleges are still struggling with this role. Assessing the clinical implications of a warning has a fairly long time frame, and time is of the essence in getting safety information out.
Getting information to Consumers
Consumers should be personally notified if there's a new drug alert. How to do this?
- Database of all relevant patients e.g. patients with cancer. (Could be a logistical nightmare.)
- Filter by therapeutic area, e.g. cancer, high blood pressure.
- Posting alerts on web site of groups affected e.g. disease advocacy groups.
- Could end users select what they want to receive? (At present there's no system for that.)
- Build on information infrastructures now in place, e.g. retail & hospital pharmacies. Augment by making use of innovative channels such as public libraries.
Challenges:
- How to inform the public without alarming them unduly, or crying wolf.
- Balance between what people want, what it costs and when people need.
- Could we use a risk stratification system? It's hard to make these judgment calls. It's now being done to an extent - HC is working on risk communication projects.
- Who should do it? Voluntary sector has the channels but not the resources.
- What about information from the drug approval process? Should Health Canada get involved beyond what is currently reported via the media?
Information should help consumers contextualize what warnings mean to their daily lives and management of their conditions. ADR and drug safety info should be meshed with patient education material on an ongoing basis.
Warnings should be in lay language.
- Advocacy groups could help translate warnings into user-friendly language.
- Translation to other languages and cultures - needs to be done by people who know the culture.
- Information should not be on-line only; hard copies should also be available.
There should be a co-ordinating body, like the consumer drug information database recommended by the National Forum on Health.
Role of the media
- Some are more responsible than others.
- They are essential part of communications plan - work out a system for feeding stories to the good guys.
- Initiate a complaints process for media that report drug information irresponsibly.
Discussion Report #37
Topic : Are we learning from other regulatory agents worldwide?
Initiator : Kennedy Mang'era
Participants : Kennedy Mang'era, Pier-Giorgio Fontana, Mario Simard, Mike Ward, Daniel Kohoko, Anon.
Discussions, proposals, actions
Motivation
Initiator is from the radiopharmaceuticals field - considered a niche market. There have recently been very divergent approaches in the regulatory processes for positron emitting radiopharmaceuticals by Health Canada and the FDA, in particular with the radioactive product 18F-fluorodeoxy glucose (FDG). It is believed that the FDA approach was more facilitative whilst that of Health Canada has been burdensome to the Nuclear Medicine community and to patient access.
FDG is a diagnostic product that is injected in very small (tracer) amounts and has been used extensively clinically used in Europe and the US, and after use in > a million patients is known to have a very good safety profile.
A key difference in approach:
- The FDA utilised scientific literature to make the regulatory determination that FDG is safe and efficacious, allows submissions to reference this determination, and therefore has simplified the approval process. Health Canada still requires clinical trials, believed by professionals to be an unnecessary burden.
Extensive information on the current and evolving approach to international collaboration was shared by Health Canada attendees and discussions were centred on these.
Key points:
- Canada has to-date memoranda of understanding and/or treaties with a number of countries, and ongoing interactions are geared towards deepening these relationships and better defining them (some of the countries -Australia, USA, Singapore, China, and Switzerland).
- There is strong current commitment at HC (especially at ADM level) for greater and closer international collaboration. And there is also good international appreciation for greater inter-jurisdictional collaboration. However, there is strong need to get to the NEXT LEVEL.
- Avenues - information sharing, cooperative projects, joint work sharing, parallel review, mutual recognition.
- No other country has a progressive licensing framework, but some incorporate various aspects of the framework.
- Progressive licensing should have ability to consolidate a drug's lifecycle data rather than treat pre- and post-approval data as separate.
- Health Canada does not have an innovation mission - different from Europe and USA where this is explicit.
- Health Canada can utilise publicly available information of other jurisdictions, and can with the consent of the manufacturer obtain and consider foreign assessment reports.
- It is preferable that Canada retains the prerogative to arrive at an independent decision on drug submissions even where the evaluation process is joint, parallel or facilitated by other jurisdictions. This promotes the principle that Health Canada is directly accountable to the Canadian people for the decision.
Current handicaps to international collaboration:
- Issues around confidentiality and consent for sharing of information with other jurisdictions. It was noted that the USA is not legally required to seek consent prior to sharing information, except for information relating to trade secrets.
- Current Health Canada legislative framework and regulations are fairly dated and do not give sufficient flexibility.
Discussion Report #38
Topic : Educating Patients/Public on Evaluation and Assessment of Drugs
Initiator : Durhane Wong-Rieger
Participants : Sylvie Cantin, Muna Idris, Maurica Maher, Karen Timmerman
Discussions, proposals, actions
There was overall discussion around the need for patients and the public to be better informed about the drug evaluation and assessment process for approval and funding. There are increasingly opportunities for patients and public to participate on advisory panels and decision making committees at various levels. Health Canada has done a lot to stimulate this process over the past several years in their consultations and advisory groups. Patients have been included in various policy and consultation forums. Recently, CEDAC (CADTH) added to public members to their expert drug advisory committee. Ontario has called for patients on its Committee to Evaluate Drugs and to set up a Community Council after the model of NICE in the UK. The concern is that patients and public need to be better prepared to serve as effective members on these councils. Similarly, there is an increasing interest among the public as we increase transparency and make information about drugs and their evaluation more accessible.
Issues:
Advocacy groups make requests for support but not necessarily those that could be funded.
Groups don't come with information and an approach that can be understood or appreciated by others.
Selection process for participants in current advisory groups is very lengthy, including nomination and posting and selection.
Level of information that can be shared with those in groups is sometime very limited; not approved for full data sharing.
Barriers include sustaining initiatives and education.
Current practices:
Information sessions on drug approval process to the general (interested) public.
Need for more in-depth information to other sectors of public.
Citizen Network (Health Canada): intention was to set up a group that could be used to provide the perspective of the general public. There was some intent not to educate "too much" since they might no longer reflect a less informed public.
There is a need to provide basic training to all group members.
Sometimes even the "scientific" members need to have education on other aspects that they may not be familiar with, for example, approaches other than clinical trials for evaluation.
Different science groups come with different knowledge backgrounds.
Potential strategies
Introductory training for all advisory group/panel members could be provided to all; this would also be less likely to differentiate the patient members.
Goal is to engage interested individuals and those representing organizations. Education and training is like a pyramid, with education at the broadest general public level the most general and basic; education aimed at a middle level of "interested individuals" and organizations that would be more technical and specific; and education at the top level very specific for those who will join the advisory groups or panels. It may be beneficial to train a large group of that "middle" level of interested individuals and participants who would then have the opportunity to be selected for more specific advisory groups and panels. It would also provide more of a focus and rationale for these individuals to participate in training and education (rather than just knowing). Prior to conferences or forums, even like this one, there could be preparatory meetings for patients/public (and others) to better prepare them for both the content and process, including background on the system, if needed.
This would also serve the need of patient representatives who often feel they need to reflect the opinions of their constituents but have never had an opportunity to discuss the issues with others in their group or with the broader patient community. A preparatory meeting specifically for patients/public would also help to broaden the education around the specific topic or issue.
Pre-meeting teleconferences, maybe locally convened, would also serve the purpose of of preparing patient participants and allow an opportunity for questions or dialogue. Pre-meetings may allow for more democratic participation in advisory groups or conferences.
A barrier is the lack of visibility and relevance of Health Canada to the patient and public communities. Health Canada needs to take a more proactive role in communicating to the public. Marketing and outreach should be specific to a health issue, rather than just promoting Health Canada or making it more visible. There was considerable discussion around health promotion campaigns that have had tremendous public impact, such as "drinking and driving", smoking, and safe sex (using condoms) that have significantly changed behaviours. These have been effective because they have engaged all sectors and levels, including the healthcare professionals and groups. They have also been carried out for a period of time, despite some initial concerns around impact.
What would be the value or outcome for Health Canada to engage in educating patients/public about the drug system? Beyond the impact of public satisfaction, what would be a desirable outcome that is "marketable" to both the funders (government) and to the public? Perhaps the most important would be "better or more appropriate use of drugs." This is an outcome that has inherent benefit from the point of view of drug safety, so people are aware of adverse reactions and taking drugs safely. It would also have appeal to the provinces who would be concerned about people not taking drugs unnecessarily. An example is the antibiotic awareness campaign directed at both patients and physicians to reduce the "over-use" of antibiotics, setting up resistance.
There is a patient/public interest in assuring that people do take drugs appropriately, for example, not abandoning drugs because of an adverse reaction or not getting an immediate desired effect (or quitting before using all of the medication).
By engaging the provinces, patient groups, and individuals, there would be greater likelihood of success. If Health Canada is seen as taking a lead and proactive in outreach and communications, it would help to develop the public perception of Health Canada as a valuable resource and as a partner to the patient and public community. This would help to increase trust in system and a willingness to learn more and to participate.
An interesting outcome would be greater public support for Health Canada, that is, Friends of Health Canada.
