FDA finally admits need for large safety studies premarketing
For the last few years, I have held an opinion contrary to most of my colleagues in the industry–that sponsors should be required to conduct large (simple) safety studies prior to marketing authorization for drugs intended to be used chronically in large, especially elderly, populations. Such studies would have as their primary goal a safety evaluation including a systematic assessment (including independent adjudication) of fatal and serious, nonfatal adverse events. See my prior posts, here and here for arguments I have proffered to support this judgment.
While I have seen limited softening of contrary opinion among my industry colleagues, there has been much more progress towards my viewpoint by regulators. Consider an interview John Jenkins, FDA’s Office of New Drugs director, gave to Reuter’s Health the other day. The piece focuses on heart safety, but the sentiments apply to chronic safety in general, with heart safety being the most urgent need. Jenkins stated that FDA is ”changing how we look at how much data you need to get a drug approved” and that FDA “might look at more requirements for large studies after approval.”
It appears that drugs used to treat hyperglycemia in Type 2 diabetes will be the first to benefit (or suffer from, depending on your viewpoint) FDA’s revised view towards premarket risk evaluation. Clearly, any new study requirements before launch will increase the cost and time to market for such drugs beyond historical norms. No one likes to see longer more expensive drug programs, certainly not me. But before condemning the coming changes for this reason, it is necessary to consider the positives to patients and to sponsors.
Liability risk
If drugs are properly vetted prior to marketing, sponsors’ commercial liability risk should be much lower and much easier to predict than today. When I was last in Pharma in 2003, liability risk wasn’t even a consideration during portfolio planning. These days, sponsors that don’t consider liability risk when determining the relative value of products in the pipeline are rightfully considered neglectful or naive. Being able to better predict liability risk should improve portfolio prioritization, helping managers funnel investments to projects with the best risk-adjusted returns, for example.
Consumer confidence and industry reputation
I don’t have objective evidence to support this assertion, but it seems to me that a negative surprise goes down a lot worse with consumers than a known issue, especially when the consumers are doctors. I would bet that not only is a drug product at risk from post-launch surprises but also that the manufacturer’s brand value suffers as well. Swift manufacturer response in the form of recalls, Dear Doctor letters, and the like can mitigate negative consumer reactions, but avoiding them in the first place should do wonders to improve the public’s confidence in our industry.
Therapeutic guidance for prescribers and unexpected benefits
Large studies mean many opportunities for individual case assessment. Each case (i.e., systematically observed chronic drug use) is an opportunity to learn more about the full range of patient responses, both efficacy and safety, thereby providing sponsors with examples to use to guide clinicians in practice.
It’s been shown that clinicians rely more on their personal experiences with individual cases than aggregate study results to guide their future therapy choices; they tend to create an image of the ideal candidate for each therapy. It might be the case that offering doctors detailed descriptions from a broad variety of cases, using examples from these large, diverse study populations, will enhance prescriber marketing. This idea hasn’t been well-tested as far as I know, but it makes sense in theory.
The other side of the safety coin is benefit. And so it is likely that as many new benefits of drugs will be observed as new risks during extended premarket evaluation. From time to time, such benefits will equal or surpass the health value of the studied indication, leading to secondary indications or follow on products for different uses. Such uses discovered during a sponsored trial are significantly more valuable to manufacturers than uses discovered outside of sponsored research.
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It can’t be determined at this time whether the financial benefits of prolonging the time to market for improved safety evaluation can counterbalance the costs, but for the reasons above, there is some reason to expect at least partial mitigation of the cost impact. However, if I were a U.S. lobbyist working on behalf of PhRMA I would work diligently to convince legislators to revise the Hatch-Waxman patent restoration rules to accommodate regulatory demand for a longer clinical trial period. Specifically, the current patent restoration maximum of five years should be increased to at least seven and preferably eight years total for chronic-use drugs to ensure that sponsors maintain an adequate time period for profit generation.
