Postmarketing Safety-Related Modifications of Drugs Approved by the US Food and Drug Administration Between 1999 and 2014 Without Randomized Controlled Trials
Por:
Shepshelovich, D, Tibau, A, Goldvaser, H, Ocana, A, Seruga, B, Amir, E
Publicada:
1 ene 2019
Resumen:
Objective: To investigate whether US Food and Drug Administration approval of new drugs without randomization or an active drug comparator is associated with more postmarketing safety-related label modifications.
Methods: We searched Drugs@FDA for new drugs approved from January 1, 1999, through December 31, 2014. Drugs approved without supporting randomized controlled trials (RCTs) were matched to between 1 and 2 controls from similar therapeutic categories approved with supporting RCTs within 3 years of the reference drug. Study characteristics, regulatory pathways, and label modifications up to December 2017 were collected from drug labels. Differences in postmarketing safety modifications between cases and controls were assessed using conditional logistic regression.
Results: The study cohort included 52 drugs approved without supporting RCTs and 91 matched controls. Drug approvals not supported by RCTs were associated with lower sample size (odds ratio [OR] per 100 patients, 0.77; 95% CI, 0.68-0.87) and were more likely to receive orphan drug designation (OR, 5.10; 95% CI, 2.23-11.69), fast-track designation (OR, 4.80; 95% CI, 2.25-10.23), and accelerated approval (OR, 7.00; 95% CI, 3.14-15.60). Drugs approved without supporting RCTs were associated with more modifications in black box warnings (28.8% vs 13.2%; OR, 2.67; 95% CI, 1.13-6.27), warnings and precautions (73.1% vs 52.7%; OR, 2.43; 95% CI, 1.16-5.09), and common adverse reactions (48.1% vs 23.1%; OR, 3.09; 95% CI, 1.49-6.41).
Conclusion: Food and Drug Administration approval of new drugs without supporting RCTs is associated with more postmarketing safety-related label modifications than drugs approved with supporting RCTs. Robust postmarketing studies are required for drugs approved without supporting RCTs. Health care professionals should be vigilant for unrecognized adverse effects when prescribing these drugs. (C) 2018 Mayo Foundation Education and Research
Filiaciones:
Shepshelovich, D:
Princess Margaret Canc Ctr, Dept Med, Div Med Oncol & Hematol, Toronto, ON, Canada
Univ Toronto, Toronto, ON, Canada
Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel
Tibau, A:
Hosp Santa Creu & Sant Pau, Oncol Dept, Barcelona, Spain
Univ Autonoma Barcelona, Barcelona, Spain
Goldvaser, H:
Princess Margaret Canc Ctr, Dept Med, Div Med Oncol & Hematol, Toronto, ON, Canada
Univ Toronto, Toronto, ON, Canada
Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel
Ocana, A:
Castilla La Mancha Univ, Albacete Univ Hosp, Translat Res Unit, Reg Ctr Biomed Res CRIB, Albacete, Spain
Castilla La Mancha Univ, CIBERONC, Albacete, Spain
Seruga, B:
Inst Oncol Ljubljana, Dept Med Oncol, Ljubljana, Slovenia
Amir, E:
Princess Margaret Canc Ctr, Dept Med, Div Med Oncol & Hematol, Toronto, ON, Canada
Univ Toronto, Toronto, ON, Canada
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