U.S. President Donald Trump’s solution to high drug prices is to get drugs onto the market faster by cutting regulations at the Food and Drug Administration (FDA) by 70 to 80 percent. Earlier this year in a meeting with pharmaceutical executives, Trump said “We’re going to be cutting regulations at a level that nobody’s ever seen before.” What he’s advocating is tearing down a system that has been in existence since the thalidomide disaster of the early 1960s — and it’s a move that could impact Canadians as well.
Trump’s suggested changes are happening against a backdrop of weakened drug regulations in the U.S. and the EU — all of which leaves Canada in a precarious spot.
At present, companies largely submit the same clinical trials to Health Canada that are used by the FDA and the European Medicines Agency (EMA), and Health Canada does its own independent analysis of them before deciding that a new product is safe and effective enough to be allowed onto the market.
If companies don’t have to do randomized controlled trials for the FDA and EMA, they may not do them for the relatively small Canadian market. At one Health Canada meeting I attended about a decade ago, a pharmaceutical company representative advised Health Canada against developing “Canadian only” rules, with the implication that if it did companies might not market some drugs here.
This is a nightmare scenario for a number of reasons, one of which is that these regulations help assure doctors and patients alike that medications are effective and safe. Already, there are a substantial number of drugs that initially appear promising but eventually are shown to not be beneficial. Do we want to make this situation worse? Do doctors want to be prescribing drugs to their patients that may turn out to be useless, and do patients want to be taking them?
Even before Trump’s proposed changes, drug regulation in both the United States and the European Union has evolved to get drugs on the market faster and without the same level of evidence that was previously required. One section of the U.S. 21st Century Cures Act, which was passed in December 2016, directs the Secretary of Health and Human Services to allow biomarkers and surrogate measures — indicators that do not necessarily predict whether patients will be better off or live longer after taking the drug — and “any other method, material or measure that the Secretary determines aids drug development” to be used to approve new drugs. “Real world evidence,” including information from health care billing data and patient reported outcomes, may also start to play a prominent role in decisions about whether or not to allow new drugs on the market.
At the same time, the EMA is now piloting “adaptive pathways” to drug licensing, a model that may prove to be as problematic as the U.S. legislation. It allows new drugs for serious “unmet medical needs” to be licensed faster with just preliminary data from human trials, which would then be supplemented after approval with observational data, in some cases as an alternative to randomized clinical trials. These changes would leave both doctors and the public with much less information about the benefits and harms of drugs.
If the FDA and the EMA are both moving in this direction, where does that leave Canada? Will Canada be able to set our own standards for the evidence needed to market new drugs, or will we be forced to go along with what these larger regulatory bodies are doing? And will Canada feel pushed towards adopting the same regulatory standards as the U.S.?
This recommendation has been made before: In 2004, an Expert Advisory Committee on Smart Regulations, made up largely of business executives, advised the federal government that Canadians were losing out because Health Canada was slower than the U.S. in its drug reviews. Making the Canadian economy more efficient “require[s] the removal of regulatory impediments to an integrated North American market and the elimination of the tyranny of small differences,” reads its final report on the issue. In addition to pressure from drug companies to get their drugs to market faster, there may also be accompanying pressure from patient groups, especially those receiving funding from industry.
If Health Canada does decide to harmonize standards with the FDA or the EMA, it will need to up its game in making sure that post-marketing studies required after a drug is on the market are completed relatively quickly and that it acts decisively on negative studies.
Currently, through what’s called a Notice of Compliance with conditions (NOC/c), Health Canada can approve drugs based on preliminary evidence, provided that the pharmaceutical company agrees to submit additional studies that prove the drug works later. If those studies are negative, Health Canada has the authority to revoke the NOC/c and remove the drug from the market.
As of November 2012, it was taking about five years for companies to complete the required studies. A more recent unpublished analysis that I have done found that there are 10 drugs that have been on the market for more than six years without fulfilling the conditions of their NOC/c and three of these drugs have been sold for more than 10 years.
In at least one case, Health Canada allowed a drug to stay on the market despite poor results in follow up studies. Studies on the drug gefitinib (Iressa) showed no survival benefit in patients with non-small cell lung cancer compared to placebo. Yet Health Canada has not removed gefitinib from the market and continues to allow it to be sold.
Finally, if there are limited studies done before drugs come onto the market, how will that affect the recommendations from the Common Drug Review (CDR), which looks at the evidence and recommends which drugs provinces should cover for people under public plans, including those who receive social assistance.
If it acts too early and recommends funding and the drug later proves to be unsafe or ineffective, not only will public money have been wasted, but more importantly, patients may have been harmed. If it decides to wait, then in the post-Trump world that evidence may never come. Until there is more information and the drug turns out to be both effective and safe, patients might have been denied beneficial treatment.
Drug regulation is a combination of imperfect science and country specific historical factors. But there’s a serious risk that we will be negatively impacted by changes in the FDA. To slightly misquote Pierre Trudeau, when you are sleeping next to an elephant, you’ll be affected by every twitch and grunt.