Best practice for analysis of shared clinical trial data

Hollis, Sally; Fletcher, Christine; Lynn, F W; Urban, Hans-Joerg; Branson, Janice; Burger, Hans Ulrich; Smith, Catrin Tudur; Sydes, Matthew R.; Gerlinger, Christoph

doi:10.1186/s12874-016-0170-y

Cited by 18 publications

(15 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the trials were powered for the primary endpoint and were controlled for multiplicity for all secondary endpoints, they were not powered for the type of analyses presented here. Further, post hoc analyses are typically not adjusted for multiple comparisons as they are exploratory, rather than confirmatory in nature [19–21]. In this context, presented p -values are nominal and should be considered cautiously.…”

Section: Discussionmentioning

confidence: 99%

Early onset of efficacy with erenumab in patients with episodic and chronic migraine

et al. 2018

View full text Add to dashboard Cite

BackgroundSubcutaneous erenumab reduced monthly migraine days and increased the likelihood of achieving a ≥ 50% reduction at all monthly assessment points tested in 2 pivotal trials in episodic migraine (EM) and chronic migraine (CM). Early efficacy of migraine preventive medications is an important treatment characteristic to patients. Delays in achievement of efficacy can result in failed adherence. The objective of these post-hoc analyses were to evaluate efficacy in the first 4 weeks after initial subcutaneous administration of erenumab 70 mg, erenumab 140 mg, or placebo.MethodsThere is no generally accepted methodology to measure onset of action for migraine preventive medications. We used a comprehensive approach with data from both studies to evaluate change from baseline in weekly migraine days (WMD), achievement of ≥ 50% reduction in WMD, and proportion of patients experiencing migraine measured on a daily basis. The 7-day moving averages were overlaid with observed data.ResultsIn both studies (EM: N = 955; CM: N = 667), there was evidence of onset of efficacy of erenumab vs. placebo during the first week of treatment, which in some cases reached nominal significance. For EM the changes in WMD were (least squares mean [LSM] [95% CI]): placebo, − 0.1 (− 0.3, 0.0); erenumab 70 mg, − 0.3 (− 0.5, − 0.2) p = 0.130; erenumab 140 mg, − 0.6 (− 0.7, − 0.4) p < 0.001. For CM the changes were: placebo, − 0.5 (− 0.8, − 0.3); erenumab 70 mg, − 0.9 (− 1.2, − 0.7) p = 0.047; erenumab 140 mg, − 0.8 (− 1.1, − 0.5) p = 0.18. Achievement of ≥ 50% reduction in WMD was observed as early as Week 1 (adjusted OR [95% CI] erenumab vs placebo) in EM: erenumab 70 mg, 1.3 (1.0, 1.9) p = 0.097; erenumab 140 mg, 2.0 (1.4, 2.7) p < 0.001. A similar outcome was observed for CM: erenumab 70 mg, 1.8 (1.1, 2.8) p = 0.011; erenumab 140 mg, 1.9 (1.2, 2.9) p = 0.009. Seven-day moving averages of observed data showed each treatment arm differed from placebo by Week 1 (OR [95% CI]): in EM Day 3 for erenumab 140 mg, 0.7 (0.5, 1.0) p = 0.031 and at Day 7 for 70 mg, 0.6 (0.4, 0.8) p = 0.002; in CM: Day 6 for erenumab 70 mg, 0.6 (0.4, 0.9) p = 0.022 and at Day 7 for 140 mg, 0.7 (0.4, 1.0); p = 0.038.ConclusionErenumab showed early onset of efficacy with separation from placebo within the first week of treatment in both chronic and episodic migraine patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Early onset of efficacy with erenumab in patients with episodic and chronic migraine

et al. 2018

View full text Add to dashboard Cite

show abstract

“…38 Flaws were also concentrated in the reporting of additional analyses, such as cal mechanisms, clinical experience, and study evidence is more reliable than a post hoc analysis for determining causal association. 39 Therefore, the CONSORT statement requires authors to distinguish the predesigned confirmatory analyses from the post hoc exploratory analyses. Unfortunately, only 13 (24.5%) RCTs reported these details.…”

Section: Discussionmentioning

confidence: 99%

Adherence to the CONSORT statement and extension for nonpharmacological treatments in randomized controlled trials of bariatric surgery: A systematic survey

Liu

Chen

et al. 2021

Obesity Reviews

View full text Add to dashboard Cite

Reporting is critical for establishing the value of randomized controlled trials (RCTs).This study evaluated the adherence of bariatric surgery RCT reporting to the CONsolidated Standards Of Reporting Trials (CONSORT) statement 2010 and its 2017 extension for non-pharmacologic treatments (NPT extension). We identified all RCTs comparing bariatric surgery with conservational therapy or alternative bariatric surgery up to June 30, 2020. Reporting quality was assessed using criteria developed from the CONSORT statement and the NPT extension and scored as a percentage.The factors associated with reporting quality were explored by univariate and multivariate analysis. In total, 102 RCTs of bariatric surgery were included. The median scores according to the CONSORT statement and NPT extension were 63.3 and 26.8 of a maximum possible 100, respectively. Two-thirds of NPT extension items were reported in less than 25% of the RCTs. The median score improved over time for the CONSORT statement but not the NPT extension. A higher CONSORT score was associated with publication in core clinical journals, protocol registration, and funding. No factors associated with the NPT extension score were identified. Substantial efforts are warranted from authors, journals, registration platforms, and funders to overcome the flaws in the reporting of bariatric surgery RCTs.

show abstract

“…Recent guidance on the use and appraisal of IPDMAs [140,141], reporting standards [130], data sharing [49], and statistical techniques [128] have influenced these policies.…”

Section: Discussionmentioning

confidence: 99%

Obtaining and managing data sets for individual participant data meta-analysis: scoping review and practical guide

Ventresca

Macbeth

Clarke

et al. 2019

Preprint

View full text Add to dashboard Cite

Background Shifts in data sharing policy have increased researchers’ access to individual participant data (IPD) from clinical studies. Simultaneously the number of IPD meta-analyses (IPDMAs) is increasing. However, rates of data retrieval have not improved. Our goal was to describe the challenges of retrieving IPD for an IPDMA and provide practical guidance based on a review of the literature and practical examples and observations. Methods We systematically searched MEDLINE, Embase, and the Cochrane Library to identify publications focused on strategies to obtain IPD. In addition, we searched pharmaceutical websites and contacted industry organizations for supplemental information pertaining to recent advances in industry policy and practice. Finally, we documented setbacks and solutions encountered while completing a comprehensive IPDMA and drew on previous experiences related to seeking and using IPD. Results Our scoping review identified 16 articles directly relevant for the conduct of IPDMAs. We present short descriptions of these articles alongside overviews of IPD sharing policies and procedures of pharmaceutical companies which display certification of Principles for Responsible Clinical Trial Data Sharing via Pharmaceutical Research and Manufacturers of America or European Federation of Pharmaceutical Industries and Associations websites. Advances in data sharing policy and practice affected the way in which data is requested, obtained, stored and analyzed For our IPDMA it took 6.5 years to collect and analyze relevant IPD and navigate additional administrative barriers. Delays in obtaining data were largely due to challenges in communication with study sponsors, frequent changes in data sharing policies of study sponsors, and the requirement for a diverse skillset related to research, administrative, statistical and legal issues. Conclusions Knowledge of current data sharing practices and platforms as well as anticipation of necessary tasks and potential obstacles may reduce time and resources required for an IPDMA. Sufficient project funding and timeline flexibility are pre-requisites for successful collection and analysis of IPD. IPDMA researchers must acknowledge the additional and unexpected responsibility they are placing on study authors or data sharing administrators and should offer assistance in readying data for sharing.

show abstract

Best practice for analysis of shared clinical trial data

Cited by 18 publications

References 29 publications

Early onset of efficacy with erenumab in patients with episodic and chronic migraine

Early onset of efficacy with erenumab in patients with episodic and chronic migraine

Adherence to the CONSORT statement and extension for nonpharmacological treatments in randomized controlled trials of bariatric surgery: A systematic survey

Obtaining and managing data sets for individual participant data meta-analysis: scoping review and practical guide

Contact Info

Product

Resources

About