Your Guide to MS Treatment Approval
Why does approval for a new MS treatment take so long?
Multiple sclerosis (MS) is a complex disease that has inspired research since the late 1800s. Yet, before the 1990s, MS remained a disease with no known treatment. The five disease modifying therapies (DMTs) we have for relapsing-remitting MS today all emerged less than 20 years ago. Looking at the big picture, you could say that science takes time. You could say the same about the safeguards.
As treatments and research methods are increasingly sophisticated, efforts to ensure public safety have also become more comprehensive. The time required from testing to approval of a new therapy stretched from a couple of years in the 1960s to the present ten years plus. Waiting for the process to unfold as promising new therapies move from laboratory to the pharmacy can be both exciting and frustrating.
Exploring good ideas takes time
It all begins with a new idea. Experimental treatments are first tested in the laboratory (preclinical study) and those with the most promising results move into the clinical trial process. During human trials, more and more information is gained about an experimental treatment, its risks and how well it may or may not work.
The many phases of research
Clinical trial application
Applications to conduct a clinical trial are reviewed by Health Canada’s Health Products and Food Branch (HPFB) to ensure that the trial is properly designed and that participants are not exposed to undue risk.
Clinical trials in Canada must be conducted in accordance with Good Clinical Practices (GCP) standards, internationally accepted ethical and scientific quality criteria for designing, conducting, recording and reporting trials that involve human participation.
While clinical studies of a therapy may be limited to months or a few years, the process of recruiting participants, designing and gaining approval for a trial at each phase of research, and analyzing the data when it is gathered generally takes many years.
Pre-clinical
Research for new treatments begins with scientists developing various chemical or biological remedies. Pre-clinical studies provide important information on the potential use of the drug (or procedure) prior to testing on humans in clinical trials. If initial results are promising, further testing is performed to learn more about its effects, and to find the dosage needed to achieve the desired effect.
Phase I trials
An experimental drug or treatment is tested in a small group of people (20-80) to:
- evaluate its safety
- determine a safe dosage range
- identify side effects
Phase II trials
After initial safety has been confirmed in the Phase I trials, the experimental treatment is given to a larger group of people (100-300) to test its effectiveness and to evaluate its safety.
Phase III trials
The experimental treatment is given to large groups of people (1,000-3,000) in a randomized controlled multicenter trial that will seek to:
- confirm its effectiveness
- monitor side effects
- compare it to commonly used treatments
- collect information that will allow the experimental drug or treatment to be used safely
Given their size and long duration, Phase III trials are usually the most comprehensive step in the treatment approval process. Their results will be a key part of bringing a treatment to the public.
Phase IV trials
Also called post-marketing studies (because they are done after a drug is available to the general public), phase IV trials allow researchers to gather and assess additional information regarding the drug's risks, benefits and optimal use.
Assessing the evidence
Health Canada evaluates and monitors the safety, efficacy and quality of thousands of human and veterinary drugs, medical devices, natural health products and other therapeutic products available to Canadians, as well as the safety and quality of food in Canada.
After the results of clinical studies indicate that a new drug has potential therapeutic value that outweighs the risks (e.g., adverse effects or toxicity) that may occur with its proposed use, the manufacturer may seek authorization to sell the product in Canada by filing a New Drug Submission with Health Canada. (The clinical trials need not have been conducted in Canada.) Health Canada then screens and reviews suitable submissions.
A New Drug Submission typically involves between 100 and 800 binders of data containing scientific information about the product’s safety, efficacy and quality. It includes the results of both the pre-clinical and clinical studies, details on the production of the drug and its packaging and labelling, and information about its claimed therapeutic value, conditions for use and side effects.
Why do some treatments get fast-tracked?
Priority review status may be granted to New Drug Submissions and some medical device applications intended for the treatment, prevention or diagnosis of serious, life-threatening or severely debilitating illnesses or conditions where:
- no product is currently marketed in Canada; or
- the new product offers a significant increase in efficacy and/or significant decrease in risk, so that the overall risk-benefit profile is better than that of existing therapies.
Because there are five approved DMTs with many years of proven efficacy and safety in the treatment of MS, an experimental treatment would need to demonstrate significant benefits over established therapies to be granted priority review status.
Approval takes time
Currently, the process for the review of a drug takes an average of 12 - 24 months from the time that a sponsor submits a New Drug Submission until a marketing decision is made.
If, at the completion of a new drug review, HPFB concludes that the benefits outweigh the risks and that the risks can be reduced and/or managed, the product is issued a letter known as a Notice of Compliance (NOC) and a Drug Identification Number (DIN), as required in the Food and Drugs Act and Regulations. This allows the manufacturer to sell the product in Canada.
Even after a drug becomes available, it may take a significant amount of time before it is accepted for inclusion on provincial formularies, each of which operates independently. If and when that occurs, it becomes eligible for reimbursement through a given provincial/territorial drug benefit program, or through federal programs available for certain groups.
Safety surveillance is ongoing
Once a new drug is on the market, regulatory controls continue. The distributor of the drug must report any new information received concerning serious side effects, including failure of the drug to produce the desired effect.
Patience and persistence pay
While the wait for a promising new therapy can be long, it’s to the benefit of everyone with MS that we have safeguards in place to prevent ineffective or potentially hazardous treatments from gaining approval for widespread use. In the meantime, we are lucky to have disease modifying therapies that help delay disease progression. Have patience, and persist with your MS treatment while we await access to emerging new approaches to the treatment of MS.