For this post I want to transition back to a bit more topical discussion on health and drug discovery. One of the issues that I’ve been reading about recently, and that you might have been reading about, Is the idea of the “Right to Try” Act that has just been passed. This act of congress allows terminally ill patients to directly contact drug companies to receive drugs that have passed Phase I FDA clinical trials but do not have full FDA approval. What’s been weighing on my mind is the thought of whether or not this is a good thing for the patients that it hopes to help. There are two points that I think we need to discuss with this topic: whether or not there is a need and also whether or not it will work. It’s hard to see exactly what might happen, if anything, as a result of this act being passed but it brings up the topic of clinical care vs clinical trials which I think we should discuss.
Firs let’s ask the question: “Is there a need for this act”. According to the “Right to Try” website sponsored by the Goldwater Institute: “Over 1 million Americans die from terminal illness each year” (1). That seems like a large number! Furthermore, the Goldwater Institute also claims: “Fewer than 3% of clinically ill patients gain access to investigational treatments through clinical trials”. Okay so what does this mean? What’s being said here is that, of that 1 million or so people, only about 30,000 are getting drugs? Does this mean that, without regulations, all 1 million people could get drugs? The answer to that is a yes and no. The writers for the website Biospace looked into the frequency of investigational drugs being given to patients through the current FDA “compassionate use” program. They noted that “the FDA receives about 1000 annual requests for compassionate use and approves about 99% of the time” (2). So while the raw numbers may be concerning (1 million people), the cases of terminally ill patients that can actually benefit from investigational drugs may actually be fairly low.
Regardless of the numbers, could these drugs actually help people? We need to ask ourselves that question. To answer this we need to think about the fact that we’re taking drugs that have passed Phase 1 FDA clinical trials. Phase 1 clinical trials in humans means that the drugs will not actively kill or harm you at the doses that are potentially useful. A recent review paper from Borysowski et al in 2016 summarized the frequency rates of these drugs going all the way through clinical trials. The authors noted that from a compilation of other studies, “probability of a drug in clinical testing eventually being approved was as low as 11.83%” and furthermore that “lack of efficacy [accounted for] 35.3% of failures”. This means that 35% of the drugs in these studies, that got past Phase 1 trials, failed because they were not efficacious; they simply did not work. Still there is a non-zero chance of the drugs actually helping people. It’s difficult to find information related to patient outcomes related to compassionate use because drug companies are not required to publish that information. One could imagine however, that there are some cases in which patients have actually been cured by such drugs.
So what’s the verdict on Right to Try legislation? I think that, as it’s written, the law makes sense and that there’s very little direct risk to patient’s health. Drugs that pass Phase 1 clinical trials should be mostly safe to use if not particularly effective. In my personal opinion the main problem comes from an increased blurring of the line between Clinical Care, and Clinical Research. These are two entirely different things. Clinical Care means that someone is proscribing you a treatment with the goal of improving your health. Clinical Research means that someone is proscribing you a treatment with the goal of getting a drug through the FDA approval process. This is why the FDA and review boards exist: to make sure that people realize what they are getting themselves into with a clinical trial. Now, with Right to Try, we’ve created a weird group that is not quite getting Clinical Care but also explicitly not involved in Clinical Research. This puts doctors in a bit of a bind as well. A doctor needs to consider the liability surrounding compassionate use. They need to think about whether or not they have enough of an understanding of an experimental drug to recommend it to a patient. This could lead to some grey areas concerning doctors with conflicts of interest such as being involved with the research itself.
In another recent review from 2017, Miller et al make a good point in suggesting that “ Legislative efforts should also aim to expand patient access to clinical trials, which in some cases could alleviate the need for expanded access and compassionate use programs” (4). Perhaps this is a complementary way forward that we should consider as well. Expanding patient sign up programs with subsidies, building avenues for patient transport to studies, and increase openness about the efficacy of clinical trials as they are happening could all lead to the same or better outcomes as compassionate use. Overall, I personally find that this legislation probably provides both little risk but also little benefit. It’s a good thing that we’re considering the role of regulatory agencies in drug development. If nothing else we should keep the conversation going.
Thanks again for reading. Again, I’ll be setting up the lab soon and meeting with new people. I start sharing those experiences very soon as well!
- Goldwater Institute, 2018, http://righttotry.org/faq/ Accessed 06/01/2018
- Biospace, 2018, https://www.biospace.com/article/right-to-try-law-and-fda-face-criticism-from-law-s-author/?utm_campaign=Newsletters&utm_source=hs_email&utm_medium=email&utm_content=63436544&_hsenc=p2ANqtz-8L780WbA4697q2DeSbAg_lzRwrt6_FoPB1q_rky9t7i0HEh967ZID4vXUOTZWLaXlsdvasLuktDSxQVgs_isma6P5MBg&_hsmi=63436544 Accessed 06/01/2018
- Borysowski J, et al. Ethics Review in compassionate use. BMC MED, 15:136, 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523146/#CR30
- Miller JE et al. Characterizing expanded access and compassionate use programs for experimental drugs. BMC Res Notes 10:350 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534121/