Adverse Event Reporting in Clinical Trials of Finasteride
A new meta-study finds the following:
“Of 34 clinical trials, none had adequate safety reporting, 19 were partially adequate, 12 were inadequate, and 3 reported no adverse events. Funnel plots were asymmetric with a bias toward lower odds ratio for sexual adverse effects, suggesting systematic under detection…”
From Wiki definition: A meta-analysis comprises statistical methods for contrasting and combining results from different studies in the hope of identifying patterns among study results, sources of disagreement among those results, or other interesting relationships that may come to light in the context of multiple studies.[1] Meta-analysis can be thought of as “conducting research about previous research.”
The report is interesting but a Meta Analysis is only as good as the clinical trials it is analyzing. All studies have its advantages and pitfalls. If adverse or sexual side effects were being examined, I question why other (much larger and comprehensive clinical trials) of finasteride 5mg was excluded.
This seems a little concerning…
As someone who has been in the biotech industry for over 30 years
(overseeing clinical trials), the above post is lacking detail (and
unreferenced) that would make it easier to understand. But, I do
believe the poster’s observation, with some very important caveats. As
Dr R notes, a meta-analysis is only as good as a trial it is
evaluating. I have observed poorly conducted trials, most often
“investigator-initiated” (university professor) rather than an
industry-sponsored trial for drugs where marketing approval is sought.
With thousands of clinical trials, and many more supporting drug
approval, I suspect the above clinical trials are early-stage and
poorly done and not ones that are considered ‘pivotal” phase 3
trials supporting drug approval. The latter studies undergo extreme
scrutiny by the regulators evaluating the trials (as evidenced by the
submission packages that are freely available on the FDA web site).
Even in an early-stage study I have never heard of a trial with no
adverse events, given that an adverse event is any untoward change
regardless of causality (ie, someone can hit their leg on a table and
have pain for 2 seconds and that is an adverse event). Finally, if the
above quotes refer to sexual adverse events only, the key piece of
info (how many patients were in the meta-analysis) is missing. With a
2-5% rate of an event, an uncontrolled trial of 30 patients is going
to miss certain events on average that a controlled trial of 4000
patients would not. Finally, how an investigator asks about adverse
events (open-ended vs. checklist) has been shown to influence the
number of events reported and is another critical feature that should
be considered in a meta-analysis evaluating rates of adverse events
(assuming that the study populations are similar, which also
influences reporting. If the “take away” message from the post above
is that finasteride trials may underrepresent sexual advrese events, I
would suspect that the above met-analysis did not include well-sone
pivotal trials (by the nottaion that “none had adequate” safety
reporting.
I was able to locate the article that forms the basis of the post; it
is published in the April edition of JAMA Dermatology and is freely
available to readers at:
https://www.ncbi.nlm.nih.gov/pubmed/?term=belknap+finasteride
A well-written article but needs proper interpretation. As I suspected
(and noted in my earlier comment), most of the trials were small
studies conducted by academic investigators (at universities) not
seeking drug approval (rather than large, pivotal studies by drug
companies). The “funding” column in Table 1 does not allow this
distinction as many academic investigators doing their
“investigator-initiated trials” may still receive funding from a
drug company. But, academic-initiated drug studies – which are not
submitted to regulators – are not overseen by drug companies,
conducted completely indepently, and often do vary in safety reporting
methods. In the case of finasteride and alopecia, I would consider the
studies in the finasteride label to be more informative than, for
example, an academic center’s 33-patient open-label study (Example 3
in Table 1).