Dataset Information

Effects of the endpoint adjudication process on the results of a randomised controlled trial: the ADVANCE trial.

ABSTRACT:

Background

Endpoint adjudication committees (EPAC) are widely used in clinical trials. The aim of the present analysis is to assess the effects of the endpoint adjudication process on the main findings of the ADVANCE trial (Trial registration: ClinicalTrials.gov NCT00145925).

Methods and findings

The ADVANCE trial was a multicentre, 2 × 2 factorial randomised controlled trial of blood pressure lowering and intensive blood glucose control in 11140 patients with type 2 diabetes. Primary outcomes were major macrovascular (nonfatal myocardial infarction, nonfatal stroke and cardiovascular death) and microvascular (new or worsening nephropathy and retinopathy) events. Suspected primary outcomes were initially reported by the investigators at the 215 sites with subsequent adjudication by the EPAC. The EPAC also adjudicated upon potential events identified directly by ongoing screening of all reported events. Over a median follow-up of 5 years, the site investigators reported one or more primary outcomes among 2443 participants. After adjudication these events were confirmed for 2077 (85%) with 48 further events added through the EPAC-led database screening process. The estimated relative risk reductions (95% confidence intervals) in the primary outcome for the blood pressure lowering comparison were 8% (-1 to 15%) based on the investigator-reported events and 9% (0 to 17%) based on the EPAC-based events (P for homogeneity = 0.70). The corresponding findings for the glucose comparison were 8% (1 to 15%) and 10% (2% to 18%) (P for homogeneity = 0.60). The effect estimates were also highly comparable when studied separately for macrovascular events and microvascular events for both comparisons (all P for homogeneity>0.6).

Conclusions

The endpoint adjudication process had no discernible impact on the main findings in ADVANCE. These data highlight the need for careful consideration of the likely impact of an EPAC on the findings and conclusions of clinical trials prior to their establishment.

SUBMITTER: Hata J

PROVIDER: S-EPMC3563633 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effects of the endpoint adjudication process on the results of a randomised controlled trial: the ADVANCE trial.

Hata Jun J Arima Hisatomi H Zoungas Sophia S Fulcher Greg G Pollock Carol C Adams Mark M Watson John J Joshi Rohina R Kengne Andre Pascal AP Ninomiya Toshiharu T Anderson Craig C Woodward Mark M Patel Anushka A Mancia Giuseppe G Poulter Neil N MacMahon Stephen S Chalmers John J Neal Bruce B

PloS one 20130204 2

<h4>Background</h4>Endpoint adjudication committees (EPAC) are widely used in clinical trials. The aim of the present analysis is to assess the effects of the endpoint adjudication process on the main findings of the ADVANCE trial (Trial registration: ClinicalTrials.gov NCT00145925).<h4>Methods and findings</h4>The ADVANCE trial was a multicentre, 2 × 2 factorial randomised controlled trial of blood pressure lowering and intensive blood glucose control in 11140 patients with type 2 diabetes. Pri ...[more]

PMID: 23390553

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Project description:ObjectiveTo evaluate the effect of a video decision support tool on the preferences for future medical care in older people if they develop advanced dementia, and the stability of those preferences after six weeks.DesignRandomised controlled trial conducted between 1 September 2007 and 30 May 2008. Setting Four primary care clinics (two geriatric and two adult medicine) affiliated with three academic medical centres in Boston.ParticipantsConvenience sample of 200 older people (>or=65 years) living in the community with previously scheduled appointments at one of the clinics. Mean age was 75 and 58% were women.InterventionVerbal narrative alone (n=106) or with a video decision support tool (n=94).Main outcome measuresPreferred goal of care: life prolonging care (cardiopulmonary resuscitation, mechanical ventilation), limited care (admission to hospital, antibiotics, but not cardiopulmonary resuscitation), or comfort care (treatment only to relieve symptoms). Preferences after six weeks. The principal category for analysis was the difference in proportions of participants in each group who preferred comfort care.ResultsAmong participants receiving the verbal narrative alone, 68 (64%) chose comfort care, 20 (19%) chose limited care, 15 (14%) chose life prolonging care, and three (3%) were uncertain. In the video group, 81 (86%) chose comfort care, eight (9%) chose limited care, four (4%) chose life prolonging care, and one (1%) was uncertain (chi(2)=13.0, df=3, P=0.003). Among all participants the factors associated with a greater likelihood of opting for comfort care were being a college graduate or higher, good or better health status, greater health literacy, white race, and randomisation to the video arm. In multivariable analysis, participants in the video group were more likely to prefer comfort care than those in the verbal group (adjusted odds ratio 3.9, 95% confidence interval 1.8 to 8.6). Participants were re-interviewed after six weeks. Among the 94/106 (89%) participants re-interviewed in the verbal group, 27 (29%) changed their preferences (kappa=0.35). Among the 84/94 (89%) participants re-interviewed in the video group, five (6%) changed their preferences (kappa=0.79) (P<0.001 for difference).ConclusionOlder people who view a video depiction of a patient with advanced dementia after hearing a verbal description of the condition are more likely to opt for comfort as their goal of care compared with those who solely listen to a verbal description. They also have more stable preferences over time.Trial registrationClinicaltrials.gov NCT00704886.

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Project description:BackgroundResearch has highlighted the need for evidence-based interventions to improve paediatric advance care planning (pACP) in adolescents with cancer. Although adolescents express the desire and ability to share their values, beliefs and preferences for treatment, there is a lack of structured multicomponent interventions to improve parent-adolescent communication on different ACP themes including those not limited to end-of-life care. The aim of this study is to evaluate the effectiveness and implementation, context and mechanisms of impact of a novel ACP program in paediatric oncology.MethodsWe will conduct a multi-centre parallel-group randomised controlled superiority trial with embedded mixed-methods process evaluation in Flanders, Belgium. Adolescents aged 10-18 who have cancer, and their parent(s) will be recruited via all four university hospitals in Flanders, Belgium, and support groups. Families will be randomised to receive care as usual or the multicomponent BOOST pACP program, consisting of three conversation sessions between an external facilitator and the adolescent and parent(s). The primary endpoint is improved parent-adolescent communication from the perspective of the adolescent. Secondary endpoints are adolescents' and parents' attitudes, self-efficacy, intention and behaviour regarding talking about ACP themes with each other, parents' perspective of shared decision making in the last clinical encounter, and the paediatric oncologist's intention and behaviour regarding talking about ACP themes with the family. Measurements will be performed at baseline, at 3 months and at 7 months using structured self-reported questionnaires. We will perform a process evaluation in the intervention group, with measurement throughout and post-intervention, using structured diaries filled out by the facilitators, interviews with facilitators, interviews with involved paediatric oncology teams, and audio-recordings of the BOOST pACP conversations.DiscussionThe BOOST pACP program has been developed to stimulate conversations on ACP themes between parent(s) and the adolescents, simultaneously lowering the threshold to discuss similar themes with healthcare professionals, initiating a process of normalization and integration of ACP in standard care. This combined outcome and process evaluation aims to contribute to building the necessary evidence to improve ACP in paediatric oncology.Trial registrationThe study is registered at ISRCTN, ISRCTN33228289 . Registration date: January 22, 2021.

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Dataset Information

Effects of the endpoint adjudication process on the results of a randomised controlled trial: the ADVANCE trial.

Background

Methods and findings

Conclusions

Publications

Effects of the endpoint adjudication process on the results of a randomised controlled trial: the ADVANCE trial.

Similar Datasets

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