Browsing by Author "Rockhold, Frank"

Now showing 1 - 11 of 11
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    Access to patient-level data from GlaxoSmithKline clinical trials.
    (N Engl J Med, 2013-08-01) Nisen, Perry; Rockhold, Frank
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    Bumps and bridges on the road to responsible sharing of clinical trial data.
    (Clin Trials, 2014-02) Berlin, Jesse A; Morris, Sandra; Rockhold, Frank; Askie, Lisa; Ghersi, Davina; Waldstreicher, Joanne
    BACKGROUND: Sharing data from clinical trials could assist with the advancement of science and medicine, potentially providing a better understanding of both the benefits and risks of medicines and other treatments. Sharing data also allows for questions to be addressed at the meta-analysis level that cannot be addressed within individual studies. PURPOSE: In this article, we offer some practical recommendations that will allow researchers to readily combine datasets from different studies and sources, thereby enabling meta-analyses that could have significant impact on advancing medicine. METHODS: The authors relied on their collective experience in the conduct and reporting of clinical trials to define the areas of potential concern related to responsible sharing of clinical trial data. We conducted a review of the literature and engaged in an iterative consensus-building process. RESULTS: To further the goal of responsible sharing of clinical trial data, collaboration on a consistent set of data standards and methods across both industry and academia is sorely needed. Protection of participant privacy is a paramount principle. The additional questions of who maintains, funds, and oversees databases of participant-level data will be important to resolve. Requiring researchers to register their requests for participant-level data and to provide details of their intended research would allow others to evaluate the proposed research plan, consistent with the principles of science and transparency. LIMITATIONS: The recommendations represent the views of the individual authors. We recognize that other approaches to data sharing that have been advocated are also based on sound ethical and scientific principles.
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    Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial.
    (Lancet, 2017-05-06) Ohman, E Magnus; Roe, Matthew T; Steg, P Gabriel; James, Stefan K; Povsic, Thomas J; White, Jennifer; Rockhold, Frank; Plotnikov, Alexei; Mundl, Hardi; Strony, John; Sun, Xiang; Husted, Steen; Tendera, Michal; Montalescot, Gilles; Bahit, M Cecilia; Ardissino, Diego; Bueno, Héctor; Claeys, Marc J; Nicolau, Jose C; Cornel, Jan H; Goto, Shinya; Kiss, Róbert Gábor; Güray, Ümit; Park, Duk-Woo; Bode, Christoph; Welsh, Robert C; Gibson, C Michael
    BACKGROUND: Dual antiplatelet therapy (DAPT), aspirin plus a P2Y12 inhibitor, is the standard antithrombotic treatment following acute coronary syndromes. The factor Xa inhibitor rivaroxaban reduced mortality and ischaemic events when added to DAPT, but caused increased bleeding. The safety of a dual pathway antithrombotic therapy approach combining low-dose rivaroxaban (in place of aspirin) with a P2Y12 inhibitor has not been assesssed in acute coronary syndromes. We aimed to assess rivaroxaban 2·5 mg twice daily versus aspirin 100 mg daily, in addition to clopidogrel or ticagrelor (chosen at investigator discretion before randomisation), for patients with acute coronary syndromes started within 10 days after presentation and continued for 6-12 months. METHODS: In this double-blind, multicentre, randomised trial (GEMINI-ACS-1) done at 371 clinical centres in 21 countries, eligible patients were older than 18 years with unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) or ST segment elevation myocardial infarction (STEMI), with positive cardiac biomarkers and either ischaemic electrocardiographic changes or an atherosclerotic culprit lesion identified during angiography. Participants were randomly assigned (1:1) within 10 days after admission for the index acute coronary syndromes event to either aspirin or rivaroxaban based on a computer-generated randomisation schedule. Randomisation was balanced by using randomly permuted blocks with size of four and was stratified based on the background P2Y12 inhibitor (clopidogrel or ticagrelor) intended to be used at the time of randomisation. Investigators and patients were masked to treatment assignment. Patients received a minimum of 180 days of double-blind treatment with rivaroxaban 2·5 mg twice daily or aspirin 100 mg daily. The choice of clopidogrel or ticagrelor during trial conduct was not randomised and was based on investigator preference. The primary endpoint was thrombolysis in myocardial infarction (TIMI) clinically significant bleeding not related to coronary artery bypass grafting (CABG; major, minor, or requiring medical attention) up to day 390. Primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02293395. FINDINGS: Between April 22, 2015, and Oct 14, 2016, 3037 patients with acute coronary syndromes were randomly assigned; 1518 to receive aspirin and 1519 to receive rivaroxaban. 1704 patients (56%) were in the ticagrelor and 1333 (44%) in the clopidogrel strata. Median duration of treatment was 291 days (IQR 239-354). TIMI non-CABG clinically significant bleeding was similar with rivaroxaban versus aspirin therapy (total 154 patients [5%]; 80 participants [5%] of 1519 vs 74 participants [5%] of 1518; HR 1·09 [95% CI 0·80-1·50]; p=0·5840). INTERPRETATION: A dual pathway antithrombotic therapy approach combining low-dose rivaroxaban with a P2Y12 inhibitor for the treatment of patients with acute coronary syndromes had similar risk of clinically significant bleeding as aspirin and a P2Y12 inhibitor. A larger, adequately powered trial would be required to definitively assess the efficacy and safety of this approach. FUNDING: Janssen Research & Development and Bayer AG.
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    Comments on ‘Estimands in clinical trials – broadening the perspective’
    (Statistics in Medicine, 2017-01-15) Rockhold, Frank
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    Data Sharing at a Crossroads.
    (N Engl J Med, 2016-09-22) Rockhold, Frank; Nisen, Perry; Freeman, Andrew
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    Issues in regulatory guidelines for data monitoring committees.
    (Clin Trials, 2004) DeMets, David; Califf, Robert; Dixon, Dennis; Ellenberg, Susan; Fleming, Thomas; Held, Peter; Julian, Desmond; Kaplan, Richard; Levine, Robert; Neaton, James; Packer, Milton; Pocock, Stuart; Rockhold, Frank; Seto, Belinda; Siegel, Jay; Snapinn, Steve; Stump, David; Temple, Robert; Whitley, Richard
    As clinical trials have emerged as the major research method for evaluating new interventions, the process for monitoring intervention safety and benefit has also evolved. The Data Monitoring Committee (DMC) has become the standard approach to implement this responsibility for many Phase III trials. Recent draft guidelines on the operation of DMCs by the Food and Drug Administration (FDA) have raised issues that need further clarification or discussion, especially for industry sponsored trials. These include, the time when DMCs are needed, the role of the independent statistician to support the DMC, and sponsor participation at DMC meetings. This paper provides an overview of these issues, based on the discussions at the January, 2003 workshop sponsored by Duke Clinical Research Institute.
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    Liability issues for data monitoring committee members.
    (Clin Trials, 2004) DeMets, David L; Fleming, Thomas R; Rockhold, Frank; Massie, Barry; Merchant, Thomas; Meisel, Alan; Mishkin, Barbara; Wittes, Janet; Stump, David; Califf, Robert
    In randomized clinical trials, a data monitoring committee (DMC) is often appointed to review interim data to determine whether there is early convincing evidence of intervention benefit, lack of benefit or harm to study participants. Because DMCs bear serious responsibility for participant safety, their members may be legally liable for their actions. Despite more than three decades of experiences with DMCs, the issues of liability and indemnification have yet to receive appropriate attention from either government or industry sponsors. In industry-sponsored trials, DMC members are usually asked to sign an agreement delineating their responsibilities and operating procedures. While these agreements may include language on indemnification, such language sometimes protects only the sponsor rather than the DMC members. In government-sponsored trials, there has been even less structure, since typically there are no signed agreements regarding DMC activities. This paper discusses these issues and suggests sample language for indemnification agreements to protect DMC members. This type of language should be included in DMC charters and in all consulting agreements signed by DMC members.
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    Moving Data Sharing Forward: The Launch of the Vivli Platform
    (NAM Perspectives) Li, Rebecca; Scott, Jessica; Rockhold, Frank; Hill, Nina; Wood, Julie; Sim, Ida
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    Open science: The open clinical trials data journey
    (Clinical Trials) Rockhold, Frank; Buyse, Marc; Bromley, Ena; Wagner, Erin
    Open data sharing and access has the potential to promote transparency and reproducibility in research, contribute to education and training, and prompt innovative secondary research. Yet, there are many reasons why researchers don’t share their data. These include, among others, time and resource constraints, patient data privacy issues, lack of access to appropriate funding, insufficient recognition of the data originators’ contribution, and the concern that commercial or academic competitors may benefit from analyses based on shared data. Nevertheless, there is a positive interest within and across the research and patient communities to create shared data resources. In this perspective, we will try to highlight the spectrum of “openness” and “data access” that exists at present and highlight the strengths and weakness of current data access platforms, present current examples of data sharing platforms, and propose guidelines to revise current data sharing practices going forward.
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    Presenting Risks and Benefits: Helping the Data Monitoring Committee Do Its Job
    (Annals of Internal Medicine) Evans, Scott R; Bigelow, Robert; Chuang-Stein, Christy; Ellenberg, Susan S; Gallo, Paul; He, Weili; Jiang, Qi; Rockhold, Frank
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    Sharing clinical trial data for research purposes.
    (Innovations & Thérapeutiques en Oncologie) Buyse, Marc; Rockhold, Frank