Wednesday, 28.10.2020

Charles M. Beasley, Jr and Roy Tamura: What We Know and Do Not Know by Conventional Statistical Standards About Whether a Drug Does or Does Not Cause a Specific Side Effect (Adverse Drug Reaction)

(Full text)

Charles M. Beasley’s final  response to Barry Blackwell’s final comment

 

        The response below is likely to be the final response to Barry Blackwell connected with our work (Beasley and Tamura 2019a,b) that was intended primarily to:  1) detail the magnitude of certainty about whether adverse events (AEs) observed in temporal association with the administration of a drug that are included in the product labeling for that drug are adverse reactions (ADRs) to that drug; and 2) remind all that might read our work and that also read the product labeling for drugs that this magnitude of certainty is much less than the magnitude of certainty regarding the efficacy of the drug for its approved indications for many of those adverse events included in the product labeling.

        We agree with Barry that the interchange with all parties involved has been polite and civilized.  We would characterize our original work, the comments and our replies as an in-depth review and exchange of information.  The series of comments and replies have not felt like a debate to us and for that, we are grateful.

        Barry, with his commentary on “Corporate Corruption in the Psychoparmaceutical Industry” (Blackwell 2016), provided the stimulus for our work and we thank him again for the stimulus.  The contents of our work were matters of great interest to Beasley during his last 15 years or so working within the industry, but if it had not been for Barry, the work would not have been written.  Beasley, at the encouragement of Tom Ban, wrote a response to that commentary by Barry (Beasley 2017) in which he provided some sample sizes for robust assessment of whether an AE observed during a randomized clinical trial (RCT) or set of RCTs was an ADR.  The sample sizes described in that response were based on 80% power and a single type of inferential analysis.  After the posting of that response, Beasley became concerned that his response was inappropriately simplistic regarding the sample sizes included in the response.  Depending on the outcome observed in a prospective RCT, and the inferential statistical method applied to the RCT results, a smaller sample size could result in a robust demonstration that an AE was an ADR.  The larger work was written with the assistance of Roy Tamura (Beasley and Tamura 2019a) along with a post-script (Beasley and Tamura 2019b) and these works were intended to provide objective and full disclosure in this somewhat complex domain.

        The larger work (Beasley and Tamura 2019a,b), the various comments and the replies to the comments have intertwined not only Barry’s commentary, Beasley’s response to that commentary, Beasley and Tamura’s longer work but also Ned Shorter’s commentary on Mellaril and QT prolongation.  QT prolongation became an intertwined topic because the Beasley and Tamura work addressed not only the sample size requirements to determine that an AE is an ADR, but a number of other topics including studies intended to demonstrate that a potential ADR is unlikely to be an ADR for a given drug.  QT prolongation, potentially leading to Torsades de Pointe (TdP) is one potential ADR for which an RCT design exists for a robust demonstration of the absence of a clinically meaningful effect predictive of TdP.

        Besides our thanks to Barry, we thank all others who have provided comments and stimulated out thinking further about these matters.

 

References:

Beasley CM. Commentary–corporate corruption in the psychopharmaceutical industry.  inhn.org.controvesies.  March 23, 2017.

Beasley CM, Tamura R.  Full Text (Charles M. Beasley, Jr., and Roy Tamura: What We Know and Do Not Know by Conventional Statistical Standards About Whether a Drug Does or Does Not Cause a Specific Side Effect [Adverse Drug Reaction]). inhn.org.ebooks.  November 21, 2019 (2019a).

Beasley CM.  A Post-Script (Charles Beasley and Roy Tamura: What We Know and Do Not Know by Conventional Statistical Standards About Whether a Drug Does or Does Not Cause a Specific Side Effect [Adverse Drug Reaction]). inhn.org.ebooks.  October 24, 2019 (2019b).

Blackwell B.   Corporate corruption in the psychopharmaceutical industry.  inhn.org.controversies.  September 1, 2016.

 

June 11, 2020