Underreporting in clinical trials and how we can increase transparency about our medicines
This is Part 1 of a segment “Transparency in Research,” which focuses on underreporting in drug development. Part 2 will focus on incidental findings.
I grabbed lunch with someone in the pharma industry one day. As we discussed the latest drug approvals, she unearthed a story that got buried. "This hasn’t been publicized," she disclosed, "but I know people who were at this company when it happened."
This company was developing a drug for autoimmunity and they started noticing that the female patients were getting pregnant. Many of these patients already had fertility issues. In fact, the link between infertility and autoimmunity is well known, so it's likely these patients were never expecting to conceive.
The researchers repeatedly came across markers for pregnancy in the routine testing for their trial, and they began to suspect that their drug had to do with it. In the process of treating their autoimmunity, is it possible the researchers reversed the infertility in some of their female patients?
That question was never investigated. In fact, the company didn't even tell the women that they were pregnant when it came up in their labs.
“Why wouldn’t the company report this information?” I asked. After all, it sounds like a positive, though unintended, side effect.
She explained that anything related to the reproductive system would flag the clinical trial to the FDA. The second they detect potential for reproductive harm, they require extra testing, which would slow down the drug approval process.
Our lunch arrived to the table, and I began to feel angry for the patients. If I didn’t think I could conceive, I would want the researchers to tell me if I was unknowingly pregnant. What if I had ordered a cocktail with that lunch?! I'm not much of a drinker, but still, you get the point.
I also thought of the people on the other side of the equation, the researchers. The entire development process for a drug approval can take years. I imagined the people working on that drug’s clinical trial and how badly they must have wanted it to get approved. How the years they invested in that project could’ve clouded their judgment.
I raise these points to redirect the focus away from the drug and back onto the people. Before we villainize pharma, we need to recognize that the science itself isn’t evil. People conduct the science and people are imperfect with all their biases and and emotional reasoning. That’s why we rely on systems of accountability.
We have these systems in place, but they’re broken. Regulatory bodies allow drug developers to cherrypick the data they report. In this revealing TED Talk, Sile Lane recounts how about half of all clinical trials on the medicines we use today have not published complete results. But that video is from 7 years ago. Haven't things changed?
While I don’t have a comprehensive history on this legislation, we can take a look at the FDA’s current oversight policy…
“Almost half a million clinical trials are registered with ClinicalTrials.gov; however, only a small portion, less than 15%, appear to be applicable clinical trials (ACTs) subject to FDA oversight of registration and results information submission requirements. Although the FDA is not tasked with enforcing the submission of results information for the more than 85% of registered trials that are not ACTs, there is an ethical obligation on the part of sponsors, trialists, and their associated institutions, to make results of trials available to the public, and this obligation can be met by submitting results information to the ClinicalTrials.gov database.” (Published December 4, 2023)
So, for 85% of registered trials, transparency is optional?! This doesn’t build my confidence in the medicines I could be taking, and I suspect it may upset you, too.
Sile Lane's 2016 TED Talk, "The hidden side of clinical trials."
To be clear, I took a look at the ACT criteria, and I don’t know whether the clinical trial discussed at lunch met all the criteria for requiring FDA oversight. But even if the company didn’t do anything illegal, that wouldn’t make me feel better! In fact, I may feel worse knowing that stories like that could happen, not just in secrecy, but out in the open under the protection of our legal system.
So, what can we do about it? Abstaining from clinical trials is not a good option in my book. That's a surefire way to slow scientific innovation and deprive ourselves of life-changing medicines.
We can, however, take action by joining trials as educated, empowered patients. You can see if your trial is an ACT by asking the research team or checking the criteria yourself. (See the hyperlink in my quote above or refer to this diagram the NIH released). And even if a trial isn’t accountable to the FDA’s oversight, you can always report to the research team’s institutional review board (IRB) when you suspect something fishy is going on.
Beyond individual trials, we can also catalyze change on a systemic level. Lane’s TED Talk highlights her campaign called AllTrials. I signed its petition, though it appears the campaign activity has gone down over the years. However, the parent organization, Sense about Science, appears to be quite active. I spotted them recently using "#alltrials" in their Tweets, so I recommend you follow them on any of their social media, if not to share their work, then to follow along with what they're doing and renew your faith that there are devoted scientists working to bring more transparency to research!
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