Safety related label changes for new drugs after approval in the US through expedited regulatory pathways: retrospective cohort studyBMJ 2017; 358 doi: https://doi.org/10.1136/bmj.j3837 (Published 07 September 2017) Cite this as: BMJ 2017;358:j3837
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It is good to read the research article “Safety related label changes for new drugs after approval in the US through expedited regulatory pathways: retrospective cohort study”.
Expedited approvals for new drugs include, “Accelerated approval pathway”, “Breakthrough therapy”, “Fast track designation”, and “Priority review”. The Food and Drug Administration (FDA) initiated “Accelerated approval regulations” in 1992, and the Federal Food, Drug, and Cosmetic Act (FD&C Act) in 2012 allowed the FDA "Accelerated approval for the drugs for serious conditions" with an unmet medical need, based on a surrogate marker or an intermediate clinical endpoint; it also included “Breakthrough therapy”[1,2]. FDA designed a “Fast track process” to facilitate the development, & a “priority review” for faster review within six months (compared to 10 months under standard review) [3,4].
Drug companies must conduct a “confirmatory trial” once the drug is on the market in an accelerated approval program and the FDA must take appropriate action regarding its approval if the drug’s safety or efficacy results are questionable .
Post-approval studies seldom cover the "deficit of knowledge" (orphan drugs) . FDA in their letters generally do not approve applications for new drugs for reasons related to safety and efficacy deficiencies . Fast-track drugs approval by the FDA is harmful and not good for the public at large, the reason being that drug companies are paying huge sums to fast-track FDA approval .
Evidence based medicine appears to be broken owing to corruption in clinical research and also to overdiagnosis harming the patients & healthy people [9,10].
Big pharma companies seem to increase the costs of drugs owing to commercial & professional vested interests and health system incentives favouring more tests and treatments .
It is not just the responsibility of regulatory bodies at a high level: responsibility starts with "Investgators who are involved in the study" and “Institutional Ethics Committees” /or “Institutional Review Boards”, which have a major role in approving the projects/RCTs. Responsibility also lies with "Sponsors/ Funders" of the projects/RCTs.
The FDA should take appropriate measures to prevent the misuse of "Expedited regulatory pathways" for the safety of patients at large. Thank you for an interesting and a relevant research article.
5. BMJ 2015;351:h5260
Competing interests: No competing interests
Re: Safety related label changes for new drugs after approval in the US through expedited regulatory pathways: retrospective cohort study
Mostaghim and colleagues  have compared expedited drugs and standards drugs by using matched pairs to determine different rates of safety related label changes. Matches were formed for pairs of drugs that had the same ATC classification (the third level of detail if possible) and were approved within three years of each other. As there were more standard drugs than expedited drugs, it is unclear if the authors have also tried to integrate more parameters, particularly the mechanism of action, to create matched pairs. Indeed, if expedited drugs corresponded mainly to first-in-class active substances (for example, rosiglitazone approved in1999 in priority review) and standard drugs to a well-known class of active substances (for example, insulin glargine approved in 2000 in standard procedure), more safety related labels changes are awaited for expedited drugs. This applies also if the expedited drug corresponds to a first-in-class active substance and the match standard drug to an active substance of the same class authorised later. To reinforce their results, the authors should provide in an appendix the matched pairs obtained in order to assess if these matched pairs make sense.
Moreover, FDA expedited programs should be seen in the light of Benefit/Risk value and not only in terms of safety issues. Uncertainties about safety in the case of the expedited procedure could be accepted if it is counterbalanced by promised benefit. There is no international criterion judging clinical added value (representing a worthwhile advantage to patients over previously available options). Nevertheless, several scoring systems like Motola’s, Ahlqvist-Rastad’s systems or government agencies [2-4] have been proposed. Using one of these systems, it would be of interest also to compare the clinical added value of the matched pairs obtained.
1. Mostaghim SR, Gagne JJ, Kesselheim AS. Safety related label changes for new drugs after approval in the US through expedited regulatory pathways: retrospective cohort study. BMJ. 2017 Sep 7;358:j3837.
2. Motola D, De Ponti F, Rossi P, Martini N, Montanaro N (2005) Therapeutic innovation in the European Union: analysis of the drugs approved by the EMEA between 1995 and 2003. Br J Clin Pharmacol 59(4):475–478
3. Ahlqvist-Rastad JBD, Beermann B, Mignot G (2004) Judging the therapeutic value of drugs: a comparison between La revue Prescrire and information från Läkemedelsverket, the bulletin of the Swedish medical products agency. Int J Risk Saf Med 16:83
4. Boucaud-Maitre D, Altman JJ. Do the EMA accelerated assessment procedure and the FDA priority review ensure a therapeutic added value? 2006-2015: a cohort study. Eur J Clin Pharmacol. 2016 Oct;72(10):1275-1281.
Competing interests: No competing interests