Dataset Information

Reporting of Cardiovascular Events in Clinical Trials Supporting FDA Approval of Contemporary Cancer Therapies.

ABSTRACT:

Background

Cardiovascular disease (CVD) has become an increasingly common limitation to effective anticancer therapy. Yet, whether CVD events were consistently reported in pivotal trials supporting contemporary anticancer drugs is unknown.

Objectives

The authors sought to evaluate the incidence, consistency, and nature of CVD event reporting in cancer drug trials.

Methods

From the Drugs@FDA, clinicaltrials.gov, MEDLINE, and publicly available U.S. Food and Drug Administration (FDA) drug reviews, all reported CVD events across latter-phase (II and III) trials supporting FDA approval of anticancer drugs from 1998 to 2018 were evaluated. The primary outcome was the report of major adverse cardiovascular events (MACE), defined as incident myocardial infarction, stroke, heart failure, coronary revascularization, atrial fibrillation, or CVD death, irrespective of treatment arm. The secondary outcome was report of any CVD event. Pooled reported annualized incidence rates of MACE in those without baseline CVD were compared with reported large contemporary population rates using relative risks. Population risk differences for MACE were estimated. Differences in drug efficacy using pooled binary endpoint hazard ratios on the basis of the presence or absence of reported CVD were also assessed.

Results

Overall, there were 189 trials, evaluating 123 drugs, enrolling 97,365 participants (58.5 ± 5 years, 46.0% female, 72.5% on biologic, targeted, or immune-based therapies) with 148,138 person-years of follow-up. Over a median follow-up of 30 months, 1,148 incidents of MACE (375 heart failure, 253 myocardial infarction, 180 strokes, 65 atrial fibrillation, 29 revascularizations, and 246 CVD deaths; 792 in the intervention vs. 356 in the control arm; p < 0.01) were reported from the 62.4% of trials noting any CVD. The overall weighted-average incidence was 542 events per 100,000 person-years (716 per 100,000 in the intervention arm), compared with 1,408 among similar-aged non-cancer trial subjects (relative risk: 0.38; p < 0.01), translating into a risk difference of 866. There was no association between reporting CVD events and drug efficacy (hazard ratio: 0.68 vs. 0.67; p = 0.22).

Conclusions

Among pivotal clinical trials linked to contemporary FDA-approved cancer drugs, reported CVD event rates trail expected population rates.

SUBMITTER: Bonsu JM

PROVIDER: S-EPMC7860639 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Reporting of Cardiovascular Events in Clinical Trials Supporting FDA Approval of Contemporary Cancer Therapies.

Bonsu Janice M JM Guha Avirup A Charles Lawrence L Yildiz Vedat O VO Wei Lai L Baker Brandee B Brammer Jonathan E JE Awan Farrukh F Lustberg Maryam M Reinbolt Raquel R Miller Eric D ED Jneid Hani H Ruz Patrick P Carter Rebecca R RR Milks Michael W MW Paskett Electra D ED Addison Daniel D

Journal of the American College of Cardiology 20200201 6

<h4>Background</h4>Cardiovascular disease (CVD) has become an increasingly common limitation to effective anticancer therapy. Yet, whether CVD events were consistently reported in pivotal trials supporting contemporary anticancer drugs is unknown.<h4>Objectives</h4>The authors sought to evaluate the incidence, consistency, and nature of CVD event reporting in cancer drug trials.<h4>Methods</h4>From the Drugs@FDA, clinicaltrials.gov, MEDLINE, and publicly available U.S. Food and Drug Administrati ...[more]

PMID: 32057377

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Project description:BACKGROUND:Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. PURPOSE:To validate results posted on ClinicalTrials.gov against publicly available U.S. Food and Drug Administration (FDA) reviews on Drugs@FDA. DATA SOURCES:ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical and statistical reviews). STUDY SELECTION:100 parallel-group, randomized trials for new drug approvals (January 2013 to July 2014) with results posted on ClinicalTrials.gov (15 March 2015). DATA EXTRACTION:2 assessors extracted, and another verified, the trial design, primary and secondary outcomes, adverse events, and deaths. RESULTS:Most trials were phase 3 (90%), double-blind (92%), and placebo-controlled (73%) and involved 32 drugs from 24 companies. Of 137 primary outcomes identified from ClinicalTrials.gov, 134 (98%) had corresponding data at Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results. Most differences were nominal (that is, relative difference <10%). Primary outcome results in 14 trials could not be validated. Of 1927 secondary outcomes from ClinicalTrials.gov, Drugs@FDA mentioned 1061 (55%) and included results data for 367 (19%). Of 96 trials with 1 or more serious adverse events in either source, 14 could be compared and 7 had discordant numbers of persons experiencing the adverse events. Of 62 trials with 1 or more deaths in either source, 25 could be compared and 17 were discordant. LIMITATION:Unknown generalizability to uncontrolled or crossover trial results. CONCLUSION:Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half the secondary outcomes, as well as serious events and deaths, could not be validated because Drugs@FDA includes only "key outcomes" for regulatory decision making and frequently includes only adverse event results aggregated across multiple trials. PRIMARY FUNDING SOURCE:National Library of Medicine.

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Dataset Information

Reporting of Cardiovascular Events in Clinical Trials Supporting FDA Approval of Contemporary Cancer Therapies.

Background

Objectives

Methods

Results

Conclusions

Publications

Reporting of Cardiovascular Events in Clinical Trials Supporting FDA Approval of Contemporary Cancer Therapies.

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