On Propecia® MDL Observations — An Interesting Comment — And An Answer

This is from a fine comment below — Original Comment:

. . .Thank you for keeping me updated with this pertinent court information. I have recently been following your blog to keep abreast of the MDL status updates.

With regard to Dr. Imperato-McGinley and the document requests- I am not sure what to make of her and the institution’s situation. 21CFR310.303 appears to place the record maintenance burden onto the new drug applicant, while other 21CFR documents require the clinical trial sponsor [not investigator] to explicitly hold certain document types from 2-10 years including financial disclosures and drug receipt/despising. I’m baffled at what she could possibly possess from the clinical trials.

On the other hand- Upon reviewing the the open-label, 5 year follow-up study I took notice to the Discussion regarding finasteride’s Safety, particularly the claims made in the first paragraph which read as: ‘At the end of the five years the percent incidences of reported sexual adverse experiences was less than the percent reported at year 1 …. [and] sexual adverse experiences are reported infrequently with continued use of finasteride’ (1). However, due to the 58% subject drop-out rate from day 0 to the end of year 5 [Editor: Emphasis supplied] this data appears a little fuzzy :

Sexual adverse experiences reported in this study were for impotence, ejaculation disorder, and reduced libido. As stated above there was a 58% subject drop-out rate from day 0 to the end of year 5. Comparing each of these three reported adverse experiences from year-5 against those from year-1yields an decrease incidence for ejaculation disorder (1.7% decrease), a decrease incidence for impotence (39.4%), and a decrease incidence for reduced libido (60.6%). It should be noted however, that such a reduction in subject numbers may not allow for true and accurate ‘excellent safety’ claims to be afforded. For example, the 60.6% reduction in reported libido from subjects day-0 to year-5 decrease in proportion to the 58% drop-out over this interval, while 1.7% decrease for reports of ejaculation disorder, and the 39.4% decrease in the reporting for reduced libido are not so proportional (increases of 34-fold and 1.5-fold, respectively).

I will let the authors of the this 5-year open-label clinical trial also author the final word here: ‘Finasteride to have an excellent safety profile and be well tolerated’.

Moore, E., (1995) Proscar(R): Five-Year Experience Eur Urol. 28:304-309. . . .

And, my answer — in part:

Quite so, Brian.

Just to be clear, it was (and is) permissible and common for the sponsor (in this case Merck/Schering Plough) to contract with the doctor’s institution (here Cornell) to be record keeper, or at least backup record keeper on trials to be submitted as part of FDA approval packets.

In that case, she and her institution might well have relevant records.

Moreover, anyone receiving AERs — or adverse event reports — is charged with certain duties to preserve and forward them, especially post FDA approval — under applicable federal rules.

She as PI (and the institution, as a CRO) might have been contacted by study participants, along these lines.

As ever — it is fair for the plaintiffs to ask — they are paying for the copies after all — and we will see.

UPDATED: I thought I’d offer a little of the FDA’s 1996 to 2014-era perspective on all of this, right here — from a pronouncement related to keeping records on all study participants — even participants who might withdraw or be disqualified from continuing in the study:

. . .FDA previously addressed the topic of data withdrawal in the preamble to the 1996 final rule providing an exception from informed consent requirements for emergency research, 21 CFR 50.24. In response to a comment that a subject’s legally authorized representative should be allowed to prevent the review of the subject’s data, FDA stated:

“FDA regulations (see, for example, Sec. 312.62 and Sec. 812.140(a)(3)) require investigators to prepare and maintain adequate case histories recording all observations and other data pertinent to the investigation on each individual treated with the drug or exposed to the device. The agency needs all such data in order to be able to determine the safety and effectiveness of the drug or device. The fact of having been in an investigation cannot be taken back. Also, if a subject were able to control the use (inclusion and exclusion) of his or her data, and particularly if the clinical investigation were not blinded, the bias potential would be immense. Thus, the agency rejects this comment because it could prevent FDA from learning of an important effect of the product and significantly bias the results of the investigation” (see comment 95, 61 Federal Register 51498, 51519, October 2, 1996). It should be appreciated that FDA’s response applies to the most potentially difficult situation, that is, studies involving an exception from the informed consent requirements in which subjects, due to a life threatening medical condition, are unable to provide informed consent to participate in the study. Subjects may subsequently withdraw from such studies, but the data collected up to withdrawal may not be removed.

[Also, s]uch review of safety data by sponsors is required by 21 CFR 312.56 and 21 CFR 812.46. . . .

There is particular concern with a study’s reliability when subjects withdraw their data in a non-random way because they are unhappy with their experience, either because they failed to obtain a desired effect or suffered an adverse event. Loss of these subjects’ data could greatly distort effectiveness results and could hide important safety information (for example, toxicity) of a poorly tolerated treatment. Allowing subjects to withdraw data could even provide an opportunity for unscrupulous parties to “improve” study results by selectively encouraging certain subjects to withdraw from a study. . . .

So it goes. . .

Namaste — and do stop back by! To one and all — have a great weekend, if we hear nothing from the court today. Smile.


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