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Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies.

ABSTRACT: OBJECTIVES:To define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs. DESIGN:Cross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies. DATA SOURCES:Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers. OUTCOME MEASURES:Trial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level. RESULTS:The FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%-100%) of trials in patients were registered, 71% (IQR 57%-100%) reported results or shared a CSR synopsis, 80% (70%-100%) were published and 96% (80%-100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%-100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries. CONCLUSIONS:Among large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track companies' transparency records and recognise exemplary companies may encourage further progress.

SUBMITTER: Miller JE

PROVIDER: S-EPMC5728266 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies.

Miller Jennifer E JE Wilenzick Marc M Ritcey Nolan N Ross Joseph S JS Mello Michelle M MM

BMJ open 20171205 12

<h4>Objectives</h4>To define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs.<h4>Design</h4>Cross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies.<h4>Data sources</h4>Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and inte ...[more]

PMID: 29208616

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Project description:ObjectivesTo investigate German physicians' attitudes towards and experiences with voluntary disclosure of payments by pharmaceutical companies in a public database and their impact on future decisions for or against disclosure.DesignA national cross-sectional survey conducted in 2018 among physicians who voluntarily disclosed at least one payment in the German transparency regulation.SettingRetrospective paper-pencil questionnaire about attitudes towards and experiences with voluntary payment disclosures in the first (2015) and second (2016) years of the German transparency regulation.ParticipantsGerman physicians who disclosed either in the first year only, the second year only, or in both years of the transparency regulation.Primary outcomes(1) The probability to disclose in 2016, predicted by physicians' experience of reactions from others in 2015, descriptive norms and attitudes towards transparency; (2) Frequency and (3) Content of reactions from others in 2015 compared with 2016.ResultsData of 234 respondents were analysed (n=42, 45 and 147 physicians who disclosed in 2015, 2016 or both years, respectively). The probability to disclose in 2016 was not predicted by perceived reactions, norms or attitudes towards transparency (p>0.01). Most participants reported not to have received any reactions by patients (190/234, 81%), colleagues (128/234, 55%) or the private environment (153/234, 65%). Neither frequency nor content of reactions differed between the first and second years (scale 1-5; frequency: Mdn 2015,2016 = 1.33 vs 1.00, r b=-0.17, p>0.01; content: Mdn 2015,2016 = 3.00 vs 3.00, r b=0.19, p>0.01). However, media reporting, fear of reputational damage and a feeling of being defamed were mentioned as reasons for non-disclosure.ConclusionsWhile confirmatory analyses did not provide significant results, descriptive analyses showed that participants who voluntarily disclose payments mainly do not experience any reactions towards their disclosures but report fears about losing their reputation due to disclosures.

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Project description:BackgroundTreatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR-TB) is expensive, labour-intensive, and associated with substantial adverse events and poor outcomes. While most MDR/RR-TB patients do not receive treatment, many who do are treated for 18 months or more. A shorter all-oral regimen is currently recommended for only a sub-set of MDR/RR-TB. Its use is only conditionally recommended because of very low-quality evidence underpinning the recommendation. Novel combinations of newer and repurposed drugs bring hope in the fight against MDR/RR-TB, but their use has not been optimized in all-oral, shorter regimens. This has greatly limited their impact on the burden of disease. There is, therefore, dire need for high-quality evidence on the performance of new, shortened, injectable-sparing regimens for MDR-TB which can be adapted to individual patients and different settings.MethodsendTB is a phase III, pragmatic, multi-country, adaptive, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of shorter treatment regimens containing new drugs for patients with fluoroquinolone-susceptible, rifampin-resistant tuberculosis. Study participants are randomized to either the control arm, based on the current standard of care for MDR/RR-TB, or to one of five 39-week multi-drug regimens containing newly approved and repurposed drugs. Study participation in all arms lasts at least 73 and up to 104 weeks post-randomization. Randomization is response-adapted using interim Bayesian analysis of efficacy endpoints. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 750 patients across 6 arms affords at least 80% power to detect the non-inferiority of at least 1 (and up to 3) experimental regimens, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per protocol populations.DiscussionThe lack of a safe and effective regimen that can be used in all patients is a major obstacle to delivering appropriate treatment to all patients with active MDR/RR-TB. Identifying multiple shorter, safe, and effective regimens has the potential to greatly reduce the burden of this deadly disease worldwide.Trial registrationClinicalTrials.gov Identifier NCT02754765. Registered on 28 April 2016; the record was last updated for study protocol version 3.3, on 27 August 2019.

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Dataset Information

Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies.

Publications

Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies.

Similar Datasets

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