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Generalizing Randomized Clinical Trial Results: Implementation and Challenges Related to Missing Data in the Target Population.

ABSTRACT: Statins are indicated in patients with elevated levels of high-sensitivity C-reactive protein and normal low-density lipoprotein cholesterol based on results of the multicountry trial, Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) (2003-2008), but the benefit in real-world populations remains unknown. We sought to generalize JUPITER results to trial-eligible population using data from the UK Clinical Practice Research Datalink (CPRD), 2001-2014. We multiply imputed missing baseline characteristics for the CPRD population and selected the trial-eligible participants as the target population based on observed and imputed values. Trial participants were weighted to be representative of the CPRD population (n = 383,418) based on individual predicted probability of selection into the trial. Trial participants were also standardized to the CPRD population without missing values (n = 2,677). In JUPITER, rosuvastatin reduced cardiovascular risk with a 3-year risk difference of -2.0% (95% confidence interval (CI): -2.9, -1.1). The rosuvastatin effect was muted in the first 2 years but remained strong at 3 years after standardizing to the imputed CPRD population (3-year risk difference = -2.7%; 95% CI: -5.8, 0.4) and the CPRD population without missing data (3-year risk difference = -1.7%; 95% CI: -3.5, 0.1). The study serves as an illustration of possible approaches to understanding generalizability of trials using real-world databases given limitations due to missing data on inclusion/exclusion criteria.

SUBMITTER: Hong JL

PROVIDER: S-EPMC5888945 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Generalizing Randomized Clinical Trial Results: Implementation and Challenges Related to Missing Data in the Target Population.

Hong Jin-Liern JL Jonsson Funk Michele M LoCasale Robert R Dempster Sara E SE Cole Stephen R SR Webster-Clark Michael M Edwards Jessie K JK Stürmer Til T

American journal of epidemiology 20180401 4

Statins are indicated in patients with elevated levels of high-sensitivity C-reactive protein and normal low-density lipoprotein cholesterol based on results of the multicountry trial, Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) (2003-2008), but the benefit in real-world populations remains unknown. We sought to generalize JUPITER results to trial-eligible population using data from the UK Clinical Practice Research Datalink (CPRD), ...[more]

PMID: 29020193

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Project description:BackgroundThe study objective was to analyse the implementation challenges experienced in carrying out the IMPROVE programme. This programme was designed to implement checklist-related improvement initiatives based on the national perioperative guidelines using a stepped-wedge trial design. A process analysis was carried out to investigate the involvement in the implementation activities.MethodsAn involvement rating measure was developed to express the extent to which the implementation programme was carried out in the hospitals. This measure reflects the number of IMPROVE-implementation activities executed and the estimated participation in these activities in all nine participating hospitals. These data were compared with prospectively collected field notes.ResultsConsiderable variation between the hospitals was found with involvement ratings ranging from 0 to 6 (mean per measurement = 1.83 on a scale of 0-11). Major implementation challenges were respectively the study design (fixed design, time planning, long duration, repeated measurements, and data availability); the selection process of hospitals, departments and key contact person(s) (inadequately covering the entire perioperative team and stand-alone surgeons); the implementation programme (programme size and scope, tailoring, multicentre, lack of mandate, co-interventions by the Inspectorate, local intervention initiatives, intervention fatigue); and competitive events such as hospital mergers or the introduction of new IT systems, all reducing involvement.ConclusionsThe process analysis approach helped to explain the limited and delayed execution of the IMPROVE-implementation programme. This turned out to be very heterogeneous between hospitals, with variation in the number and content of implementation activities carried out. The identified implementation challenges reflect a high complexity with regard to the implementation programme, study design and setting. The involvement of the target professionals was put under pressure by many factors. We mostly encountered challenges, but at the same time we provide solutions for addressing them. A less complex implementation programme, a less fixed study design, a better thought-out selection of contact persons, as well as more commitment of the hospital management and surgeons would likely have contributed to better implementation results.Trial registrationDutch Trial Registry: NTR3568 , retrospectively registered on 2 August 2012.

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Generalizing Randomized Clinical Trial Results: Implementation and Challenges Related to Missing Data in the Target Population.

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Generalizing Randomized Clinical Trial Results: Implementation and Challenges Related to Missing Data in the Target Population.

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