Health Committee on Sept. 27th, 2018

[The Chair, Liberal, Bill Casey]

I will convene our meeting number 112.

Welcome to our guests. We appreciate your taking the time to share your wisdom with us. We look forward to hearing from you.

Today we have Catherine Parker, Director General, Biologics and Genetic Therapies Directorate, Health Products and Food Branch at the Department of Health. We have Karen Reynolds, Executive Director, Office of Pharmaceuticals Management Strategies; and Dr. John Patrick Stewart, Director General, Therapeutic Products Directorate.

I believe you've been here before, have you not, in this Parliament?

[Dr. John Patrick Stewart, Director General, Therapeutic Products Directorate, Department of Health]

I have previously.

[The Chair, Liberal, Bill Casey]

Welcome, and go ahead with your opening remarks.

[Catherine Parker, Director General, Biologics and Genetic Therapies Directorate, Health Products and Food Branch, Department of Health]

Good morning.

Thank you for the opportunity to be here today to discuss Health Canada's role in maximizing the quality, safety and effectiveness of drugs for rare diseases and in making these drugs available to Canadians.

Joining me today is Dr. John Patrick Stewart, and Ms. Karen Reynolds, also of Health Canada.

Rare diseases are life-threatening, debilitating or serious and chronic conditions affecting a small number of patients. There is no international standard for the definition of a rare disease. Many definitions include prevalence or incidence of the disease being targeted. Within Health Canada we have adopted a definition similar to that used within the European Union of a rare disease being one affecting fewer than five in 10,000 Canadians. Some of these diseases are considered ultra-rare and may even affect fewer than 10 Canadians.

However, although the number of Canadians with a particular rare disease may be low, there are thousands of rare diseases, and it is estimated that as many as one out of every 12 Canadians is affected by one.

Many of these diseases are genetically based and appear at birth or in early childhood. They can lead to a shortened lifespan and reduced quality of life and can place significant challenges on patients, caregivers and the health care system.

I understand you will hear directly from patients living with rare diseases. You will hear first-hand about the difficulties they often face in getting an accurate diagnosis, which can take years and require several specialists.

I now would like to explain the role that Health Canada plays in making drug treatments for rare diseases available to Canadians in need. We are aware of the challenges associated with developing and bringing to market drugs to treat rare diseases, which Canadians often refer to as orphan drugs. These challenges include limited to no information on the natural history of the disease and small patient populations, which make it challenging to conduct the typical clinical trials that are normally necessary to support drug development.

Health Canada oversees the testing of new drugs in clinical trials and their eventual authorization for sale, as well as the post-market surveillance. This includes drugs for rare diseases. Clinical trials represent a good opportunity for rare disease patients to access treatments and to contribute to supporting research to further understand their disease and the potential therapeutic benefit of new therapies.

Health Canada reviews clinical trial applications quickly and efficiently and provides free scientific advice to drug manufacturers on the design of clinical trials in small patient populations. Once a clinical trial is authorized by Health Canada, the trial is included in the clinical trials database. This database aims to help patients and their primary care providers to find available trials and it supports the recruitment of rare disease patients.

Once a drug manufacturer has sufficient evidence of a drug's safety and efficacy, it may seek a market authorization in Canada. Health Canada issues market authorizations for drugs, following an assessment of a complete dossier of information showing that a drug is safe, effective and of high quality, that the benefits will outweigh any risks, and that the risks can be managed. Once the drug is marketed, we continue to oversee it in order to monitor the safety profile.

Drugs that are intended to treat serious or life-threatening diseases, as many rare diseases are, are accelerated through the regulatory review process and given priority status or conditional approval. These accelerated pathways provide earlier access to promising new drugs for patients suffering from rare diseases.

However, a market authorization alone will not ensure availability. Canada's health care system is complex and involves the participation of multiple stakeholders who all have distinct roles in the planning and delivery of health care services. Health Canada's decision-making role in approving a drug is distinct from the roles of those who make decisions about cost-effectiveness, price setting and drug plan reimbursements.

Unfortunately, many rare disease drugs are very expensive. Health Canada, while recognizing and protecting its distinct role, must work with all of its partners and key stakeholders to improve access to drugs for rare diseases by encouraging the development and availability of safe and effective products.

Health Canada is receiving applications and approving drugs for rare diseases. Currently 30% to 40% of all new drugs approved in Canada, as well as in international markets, such as the U.S. and Europe, are drugs for these rare illnesses. Recent research from the Patented Medicine Prices Review Board indicates that nine out of the 10 top-selling orphan drugs are available in Canada. In 2017, 16 of the 36 brand new drugs we authorized in Canada are classified as orphan drugs in Europe or the United States. Most of these were reviewed and approved using our accelerated pathways.

Drugs that are not marketed in Canada may be accessed through Health Canada's special access program. This program provides access to unapproved medications on an exceptional case-by-case basis for practitioners treating Canadians with serious or life-threatening conditions when conventional treatments have failed or are unsuitable or unavailable. Approximately 30% of the drugs authorized through the special access program are used for the treatment of rare diseases.

However, we need to do more. Many jurisdictions have specific legislation in place to incentivize the development of rare disease drugs. The orphan legislation in the European Union and the U.S. were put in place to support the development of drugs that would otherwise not be profitable to bring to market.

In 2016, Health Canada launched the regulatory review of drugs and devices initiative, a major effort to improve the availability of and access to prescription drugs, including drugs for rare diseases. This represented a significant funding initiative in budget 2017.

We understand the particular needs and challenges of Canadians with rare diseases and have made a commitment to improve access to medications that treat these conditions. The regulatory review of drugs and devices initiative will make the regulatory process more efficient and better able to meet the needs of the health care system. It will also help to ensure that patients have access to those important new medications approved by Health Canada.

We will do this by working closely with the health technology assessment bodies to reduce the time between Health Canada approvals and reimbursement recommendations. We will also work with our health technology assessment bodies to provide parallel advice to industry on clinical trial designs at an early stage of drug development.

We will consider health care system needs in making decisions about which drugs Health Canada should prioritize. We'll use existing and new real world evidence to support regulatory decision-making across a drug's life cycle.

We will determine the best way to incorporate patient input into the regulatory approval process. Health Canada recognizes the value of information gathered from patients as the direct users of these products. This is especially true for rare diseases, given the limited information available and the fact that, for some of these diseases, patients and/or their caregivers may be the best experts.

Furthermore, Health Canada is renewing and modernizing the special access program to better meet the needs of physicians and patients. Improvements have already been implemented to provide greater assistance to physicians, and other changes are planned, including a new electronic system that will streamline requests.

In addition to helping to support interested parties navigate the regulatory framework, Canada's regulatory approach to drugs for rare diseases is now described online on Canada.ca.

We have heard that recognition of the orphan status of these products is important to many stakeholders. We now identify drugs that are considered orphan drugs in Health Canada's annual new drug authorizations report, which we have brought copies of for you.

We have sufficient flexibility under our existing regulations and policies to accommodate the challenges posed by drugs for rare diseases and make them available in Canada. Our ongoing regulatory review provides us with an opportunity to continue modernizing our regulatory approach to help support getting Canadian patients the medicines they need.

Now more than ever, it is a shared priority of Health Canada and its federal, provincial and territorial partners to improve the affordability, accessibility and appropriate use of prescription drugs in order to better meet the needs of Canadians.

[The Chair, Liberal, Bill Casey]

Thanks very much.

You have six seconds left to go. That's the way we like it.

We're going to go to questions, and I have one quick question.

How do you access the special access program? What door do you go to for that?

[Catherine Parker]

I will ask Dr. Stewart to answer that question.

[Dr. John Patrick Stewart]

The special access program is meant to be accessed by practitioners who have authority in provincial jurisdictions to prescribe unapproved medication. It's a process that begins with a physician making a decision that the unapproved therapy is the best choice for the patient in front of them given their condition and the current available therapies on the market.

Once they have made a decision that the best choice would be an unapproved therapy and that they are dealing with a serious and life-threatening condition, they complete a special access program request form, which is a two-page document that has five sections to complete. They submit that to Health Canada. It's reviewed by the special access program team to ensure that the request meets the requirement of the regulations, that there is actually a serious and life-threatening condition, that the therapies available on the market have been considered and tried or are unavailable, and that there is use on the safety and efficacy of that drug available to support the authorization.

[The Chair, Liberal, Bill Casey]

Thanks very much.

Now we will go to our panel, starting with Ms. Sidhu for seven minutes.

[Sonia Sidhu, Liberal, Brampton South, ON]

Thank you, Chair.

Thank you, witnesses, for your testimony and presentation.

We know one in 12 Canadians is affected with rare diseases. Does the department look at the approval of rare disease drugs in other countries when approving those in Canada?

[Catherine Parker]

Yes, we certainly do. We're very much involved in collaboration with our international regulatory partners. At the time of a request for authorization, we consider whether a product has been approved in another jurisdiction, particularly with our partners in the United States Food and Drug Administration and the European Medicines Agency. We can get copies of any of their review reports and use them in our own decision-making.

We also participate in teleconferences with those two agencies almost on a monthly basis to discuss certain products that are in the approval process in all three, so that we share information during our review process as well.

[Sonia Sidhu, Liberal, Brampton South, ON]

The national program for newborn screening, with clear guidelines.... What do you think about DNA genomic screening? Do you think that's going to help, to screen?

[Catherine Parker]

That's a very difficult question to answer.

[Dr. John Patrick Stewart]

Certainly there's a trend in development of drugs to personalize medicine. Genomics and other markers can be used to hopefully identify subpopulations of patients with a disease where a therapy might be most beneficial, have the least number of side effects and cause the least number of problems.

This is a direction in drug development. Genomic-type testing is a big part of personalized medicines.

[Sonia Sidhu, Liberal, Brampton South, ON]

Thank you.

Some have suggested that pre-market clinical trials for drugs are not always reliable. Health risks are sometimes great.

In your experience with the challenges associated with pre-market trials for these drugs, how can the department address these challenges?

Anyone can answer.

[Catherine Parker]

I will comment and then pass it to Dr. Stewart.

We acknowledge that clinical trials have restrictions and may not reflect what happens once a drug goes into what we call real-world use. That is one of the reasons we have a conditional approval system for some of these products, where we can issue an approval of a medication on promising evidence from clinical trials, but with a commitment from the manufacturer that they are going to confirm that benefit and that safety profile once the product goes into use. That can be with confirmatory trials, registries, monitoring what happens in the actual usage and so on.

Dr. Stewart may want to add something to my answer.

[Dr. John Patrick Stewart]

I support what Cathy said. With orphan diseases—rare diseases—one of the challenges in studying drugs is the size of the population you're studying. Globally there may be fewer than 1,000 patients suffering from it.

Normally, in clinical trials that approve drugs for market authorization for sale, we're looking at phase three clinical trials with 3,000 to 5,000 patients, where statistics and the size of the studies allow us to have a better understanding of the performance and the risk associated. With rare diseases, we're talking about potentially 10, 20 or 30 Canadians with this condition.

The trials are often designed to be global, with many sites. There are challenges around who would be a controlled group and whether there is a controlled group. Often the participants are also the control group. We're faced with unique kinds of challenges around showing if there is effectiveness and safety with the drug. Globally we work on what is the evidentiary bar we would allow access to. As Cathy said, we also have to put in place conditions that allow us to continue to monitor the performance of the drug and whether the promising effectiveness that's shown in these early trials is borne out by more real-world use.

[Sonia Sidhu, Liberal, Brampton South, ON]

Thank you.

We know that this particular rare diseases group has a lot of challenges: misdiagnosis, unnecessary surgeries and financial hardship. For the orphan drugs, what were the key points of the framework? What work remains to be done to improve access to orphan drugs so more people can have access?

[Catherine Parker]

As the regulator, certainly, our priority is to make sure that as orphan drugs are being developed they come to Canada. We want to see sites in Canada for clinical trials so that patients can have access through that, and so practitioners can become familiar with the products. Also, when a company is ready to file for a market authorization, whether they're planning to file to the U.S. or the European Union, we want them file to Canada at the same time. That is the first step in access. It's to get those products through the approval system.

After that, of course, there are steps in the access chain, which we've described: the health technology assessment and also the reimbursement decisions. What we are doing within Health Canada through our regulatory review initiative is trying to bring some of those processes more into parallel rather than having them occur sequentially. Rather than an HTA proceeding after our approval, or mostly after our approval, we're trying to bring it into a parallel stream so that the regulator is working on the regulatory approval and the HTA body is working on the assessment for a funding decision at the same time, reducing some of those time lags between those. We feel that's a very important step in improving access.

Of course, there are other factors as well. Maybe my colleague Karen Reynolds could add to this.

[Karen Reynolds, Executive Director, Office of Pharmaceuticals Management Strategies, Department of Health]

Thanks very much for the question.

As Cathy was mentioning, ultimate access for many Canadians relies on a drug being reimbursed through either their public drug plan or a private plan. That's why the alignment with the health technology assessment is so important. As you're likely aware, agencies such as the Canadian Agency for Drugs and Technologies in Health and the Institut national d’excellence en santé et en services sociaux in Quebec are the ones that do these health technology assessments and make recommendations, largely to public plans at this time, in order for Canadians to have reimbursement.

The alignment that Cathy is talking about is really important, because at this time it could take several months before a drug is listed on a formulary, and patients will not have access until then, so we're trying to reduce that time and also align the evidence that both Health Canada and CADTH need, such that, again, when those processes are undertaken, they can happen faster.

[The Chair, Liberal, Bill Casey]

Thanks very much.

Ms. Gladu.

[Marilyn Gladu, Conservative, Sarnia—Lambton, ON]

Thank you, Chair, and thank you to the witnesses.

I want to preface my questions by saying that I do think that in Canada we have a good system in place that allows Canadians access to medications that many people in the world don't have access to, and I think we've created a climate where we're punching above our weight in clinical trials. What I'm going to focus on are areas where I have had situations that people in my constituency worry about.

First of all, with regard to the special access program, there were a couple of instances where individuals got hookworm when they went to the Caribbean and doctors prescribed things that were going to be available through the special access program. Both were denied. That had to be escalated to the health minister. Eventually they did get the drug, but I see that as one area where, when the doctor has prescribed it, I don't understand why people would not receive access. Hold that thought.

The second one is about people who have a lifelong condition and need a drug that's only available through special access. What's the one that...?

[Ben Lobb, Conservative, Huron—Bruce, ON]

It's Cystagon.

[Marilyn Gladu, Conservative, Sarnia—Lambton, ON]

Cystagon is one of them. They get access to the drug, but then they have to reapply every few months for their whole life. It's a lifelong condition. It just seems that's a bit of bureaucracy.

The other thing I've heard is that there are drugs that have been on the list in the special access program for 27 years. It seems that at some point, if we're comfortable with the drug, it should somehow make its way onto the provincial formularies.

Will the special access program improvements you're talking about address those three scenarios?

[Catherine Parker]

I will refer that to Dr. Stewart to answer.

[Dr. John Patrick Stewart]

The short answer is yes. The special access program has been in operation for a long time and, as I mentioned earlier, it requires a dialogue with physicians, so the physician has to determine that specific therapy is the best choice for their patient.

They submit a request; it's assessed in the program and then it's ultimately authorized. There may, at times, be problems with documentation or lack of documentation, so there may be a further dialogue. If there isn't a response, it may ultimately be cancelled. If the dialogue with the physician is such that it is determined that it's not the best therapy, then it may be withdrawn.

Actually, formal denials are 0.3%. Last year there were 13,000 requests for the special access program, and only 48 were denied, so it's very rare.

Speaking to your question about process improvements, one of the things we've done is to look at when denials happen and ask how we can make that better. In the last year or two we've actually hired additional resources with clinical expertise, so we have a clinical pharmacist who actually works in the health care system as well as working for Health Canada. Before we make any denials, currently this individual, or someone with similar skills, will contact the physician and have a dialogue. Putting this in place has dropped our denials from about 1.5% to 0.3%, so there is a conversation.

You mentioned the situation with the drugs for the skin condition, larva migrans. We can't speak to specific requests, because that is private information, but I would just say that one of the bars that used to be met is that the request has to explain why the condition is serious and life threatening, and have the documentation on the use and safety and efficacy.

Sometimes requests will come in where that isn't clear. If you have certain conditions, like infectious diseases or the type of conditions that can be self-limiting or there can be aspects where it becomes life threatening, it requires a dialogue to determine whether the situation is serious and life threatening when it's approved.

Putting in place these additional clinical contacts I think will go a long way to avoiding situations where the problem is more clarity of information between the program and the practitioner.

As for other improvements, the communication is there. We've added clinical expertise. We've actually increased the collaboration across directorates and with the bureaus involved with approving drugs. You mentioned drugs that have been on the program for a long time, and this is an area where we are focusing and we've had dialogue with industry on why these drugs aren't coming in. Is it low volume or is it marketing decisions? We're putting in place a series of incentives to try to get companies that have had their drug on the program for so long to actually come in and market the drug.

We've had some success in the last year. We've had three of the top 10 drugs that were on the program for a number of years actually come in and get market approval, so that's a lot of help for pharmacists, for physicians and for hospitals, and we continue to work on that.

The other challenge you mentioned was patients who are on drugs for a long time on the program. Again, we've looked at this and we are changing some of our processes around situations where it's likely there will be a repeat request where the authorization period could be extended.

Having said that, the program is providing access to unapproved therapies that haven't gone through a formal assessment by the regulator to look at safety, quality, and efficacy. Some of these drugs are well known, and some are not, so the hesitancy to provide a long period of approval is that really they're not at the same bar. We don't have the same understanding as we do with approved drugs on the market in Canada.