- It's understandable that unusual patients are seen as confounding variables in any study, especially those with small numbers of patients. Though I haven't read beyond the abstract, it also makes sense that larger studies (phase 3 or 4) should not exclude such patients, but perhaps could report results in more than one way -- including only those with the primary malady as well as those with common confounding conditions.
Introducing too many secondary conditions in any trial is an invitation for the drug to fail safety and/or efficacy due to increased demands on both. And as we all know, a huge fraction of drugs fail in phase 3 already. Raising the bar further, without great care, will serve neither patients nor business.
by DigitalPaladin
2 subcomments
- A relative of mine was in the late-stages of cancer, and was not able to find ANY trials willing to accept them. The worst of those trials was out of Baltimore (MD USA), and they ghosted my relative after initial in-person consults that required by relative to drive out of state. Despite the patient's repeated and dogged outreach to the trial authors after that point, there was never an explicit "no" that would let the patient move on, just radio silence instead and that felt cruel to me.
- Abstract: "The FDA does not formally regulate representativeness, but if trials under-enroll vulnerable patients, the resulting evidence may understate harm from drugs. We study the relationship between trial participation and the risk of drug-induced adverse events for cancer medications using data from the Surveillance, Epidemiology, and End Results Program linked to Medicare claims. Initiating treatment with a cancer drug increases the risk of hospitalization due to serious adverse events (SAE) by 2 percentage points per month (a 250% increase). Heterogeneity in SAE treatment effects can be predicted by patient's comorbidities, frailty, and demographic characteristics. Patients at the 90th percentile of the risk distribution experience a 2.5 times greater increase in SAEs after treatment initiation compared to patients at the 10th percentile of the risk distribution yet are 4 times less likely to enroll in trials. The predicted SAE treatment effects for the drug's target population are 15% larger than the predicted SAE treatment effects for trial enrollees, corresponding to 1 additional induced SAE hospitalization for every 25 patients per year of treatment. We formalize conditions under which regulating representativeness of SAE risk will lead to more externally valid trials, and we discuss how our results could inform regulatory requirements."
by kerkeslager
1 subcomments
- This problem is actually even worse than the article identifies, because broad definitions of what a "risk" is, result in broad exclusions.
The most pernicious of these problems is that women--yes, more than half the earth's population--are considered a high risk group because researchers fear menstrual cycles will affect test results. Until 1993 policy changes, excluding women from trials was the norm. Many trials have not been re-done to include women, and the policies don't include animal trials, so many rat studies, for example, still do not include female rats--a practice which makes later human trials more dangerous for (human) female participates.
[1] Sort of one citation: https://www.aamc.org/news/why-we-know-so-little-about-women-... There's more than this--I wrote a paper about this in college, but I don't have access to jstor now, so I'm not sure I could find the citations any more.
by RobotToaster
5 subcomments
- I've personally been excluded from several depression clinical trials for having suicidal ideations, it makes me wonder just what kind of "depression" they are testing drugs on.
- I can’t find the exact MDMA study for PTSD but after reading the study participants rejection criteria for it; it seemed like few could qualify.
I saw a new procedure available in Mexico for 8k for psychedelic treatment with Ibogaine. Still schedule 1 like MDMA in USA.
It looks like there has been a few MDMA trials for ptsd even though the FDA denied more widespread testing.
https://www.science.org/content/article/fda-rejected-mdma-as...
by Madmallard
0 subcomment
- Wonder if this is what happened to fluoroquinolones. They are likely mitochondrial toxins and some small percentage of patients get permanently harmed by them and sometimes in a severe way. Older versions were taken off the market and the current versions each have multiple black box warnings. Sadly, it seems many doctors aren’t even aware of this.
by BananaaRepublik
0 subcomment
- As a lay person, huh, that's something you don't think about. But still even if that were true, I don't see how society, patients and their caretakers will accept high risk patients in trails. And wasn't there news recently of UK phasing out animal trails too?
by nitwit005
2 subcomments
- This covers the trials not being fully representative, but largely neglects why that is the case.
The paper defines a population "at high risk of drug-induced serious adverse events", which presumably means they're also the most likely people to be harmed or killed by the drug trial itself.
by unethical_ban
0 subcomment
- This was a plot in an early season of ER.
- Tangentially related, but I was surprised to learn about the lax attitude towards placebos in trials. Classes of drugs have expected side effects, so it's common to use medications with similar effects as placebos. Last I heard, there is no requirement or expectation to document placebos used, and they are often not mentioned in publications.
by OutOfHere
3 subcomments
- Move generally, whenever you read the percentage of patients that are noted as having a particular side effect from a medicine, the real percentage is much higher.
by umitkaanusta
1 subcomments
- but how do you even convince high risk patients to join the trials?
- i would imagine to make life of the statisticians downstream easier
- See also: women.
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