Over the past few decades it’s become common practice for drug companies and drug regulators, such as Health Canada, to sit down together at what are called pre-submission meetings.
These are get-togethers where both parties talk about an upcoming application from the company. Health Canada’s Guidance for Industry on the management of drug submissions lays out some of the goals: familiarizing Health Canada’s review staff with a submission prior to its arrival, uncovering any major unresolved problems, identifying whether submitted studies are adequate, allowing Health Canada to redistribute funding if necessary.
These types of meetings sound benign or maybe actually positive. Health Canada gets to use its limited resources in the most productive way, the drug company doesn’t have to do extra unnecessary testing and, most importantly, new drugs may reach patients faster.
Moreover, if clinical trials of a new drug in humans are optimized, fewer people will be exposed to unknown risks. If trials are smaller and faster, they will be less expensive and that may mean lower drug prices.
But there are also potential downsides.
More drug safety problems
First, it’s Health Canada’s job to protect public health, not to make it less costly for companies to run trials. And the two are not necessarily synonymous. Less expensive trials are typically smaller trials, but fewer patients also means it’s harder to spot rarer side effects before drugs hit the market.
Getting through the regulatory system faster is also cheaper for drug companies, but speedier reviews equate to more safety problems once drugs are being sold. We also need to remember that in most cases Health Canada doesn’t need to rush new drugs to the market. Only about one in 10 offer a significant improvement over what’s already available.
The idea that the price of drugs is a reflection of how much companies spend on research and development has been debunked by the likes of Hank McKinnell, the former CEO of Pfizer.
Finally, if Health Canada is giving drug companies advice about how to run their trials, then will the agency feel obliged to approve those trials once they are submitted, even if they don’t convincingly show a drug to be safe and effective?
As an analogy, suppose a judge meets with the prosecutor before a trial starts, to discuss with the prosecutor how best to present her case. As the defendant, how confident would you be that the judge will be objective in coming to a decision?
In the case of Health Canada and the pharmaceutical industry, the defendant is the Canadian public.
A revolving door
These pre-submission meetings occur alongside other ongoing relationships between drug companies and drug regulators. Health Canada already gets 50 per cent of the cost of operating its prescription drug program from money that companies are obliged to pay and it wants that to go up to 75 per cent.
Regulators in other countries recover upwards of 90 per cent of their costs from companies. Although not that visible a problem here in Canada, in the United States there is a revolving door between the Food and Drug Administration and the drug industry. After Dr. Scott Gottlieb resigned as FDA commissioner his next move was to the board of Pfizer.
This type of relationship has garnered criticism in multiple different countries. When a British House of Commons Committee looked into the influence of the pharmaceutical industry on that country’s drug regulator, it concluded that the Medicines and Healthcare products Regulatory Agency (MHRA):
“… like many regulatory organisations, is entirely funded by fees from those it regulates….This situation has led to concerns that it may lose sight of the need to protect and promote public health above all else as it seeks to win fee income from the companies.”
The European Medicines Agency recently organized a consultation on pre-submission meetings. In reply the International Society of Drug Bulletins and the French drug bulletin, Prescrire wrote that, “EMA’s confidential pre-submission ‘scientific advice’ to companies jeopardises its ability to make independent decisions.” These bodies advised that:
“… experts involved in providing national pre-submission scientific advice must not be involved in any subsequent evaluation of European marketing authorisation applications for the same medicine.”
Weaker standards for approving drugs
Critics of the intertwined nature of the regulation-industry relationship claim that one of the results is that weaker standards for approving new drugs have become acceptable.
Many drugs are approved on the basis of surrogate endpoints — such as changes in the level of blood sugar or how much cancer tumours shrink — rather than outcomes that really matter to patients, such as whether they’ll have a better quality of life or whether they’ll live longer.
Half the new drugs approved come on the market without any comparison to standard therapy, leaving doctors and patients wondering whether the new drug is any better than the old one.
Is Health Canada’s relationship with drug companies the reason why one spokesperson told a reporter for the Toronto Star that the reason that it had never prosecuted a drug company for illegally marketing unapproved uses was that it “has not been made aware of any specific similar issue in Canada and has not received complaints concerning these companies promoting off-label uses of their products in Canada?”
Drug companies have a job to do and so does Health Canada. Health Canada should not confuse what those two jobs are.
Joel Lexchin, Professor Emeritus of Health Policy and Management, York University, Emergency Physician at University Health Network, Associate Professor of Family and Community Medicine, University of Toronto