Streamlined mail-based methods for large randomised trials: lessons learnt from the ASCEND study

Abstract

Reliable assessment of the effects of an intervention usually requires large randomised trials but such studies are becoming increasingly complex and costly to run. 'Streamlined' trials are needed in which every aspect of the trial design and conduct is simplified, retaining only those elements needed to answer the research question and ensure the safety of the individual participants. In this review we discuss how the trial 'A Study of Cardiovascular Events iN Diabetes' (ASCEND) was streamlined. The study included a two-by-two factorial design: it assessed the effects of low-dose aspirin and, separately, supplementation with n-3 fatty acids on serious vascular events in 15,480 people with diabetes but no overt cardiovascular disease. Other key streamlined design features, such as mail-based recruitment and follow-up, mainly by post, with no in-person visits and use of a run-in period, are also described. We go on to discuss the success of the study and other studies that have employed a similar mail-based approach, and the type of clinical trials that are suitable for mail-based design. Finally, we consider the limitations of the study, and how these could be circumvented in future studies. ASCEND randomised large numbers of eligible participants, achieved good adherence rates and almost complete follow-up at a fraction of the cost of traditional clinic-based trials. Such studies are necessary if researchers are to address the important clinical questions most relevant to improving health.

A systematic review of methods used to conduct decentralised clinical trials

“…These decentralised clinical trials (DCTs), where some or all elements of a trial are selected to reduce the need for clinical trial site attendance, aim to reduce the burden of trial participation, boost trial accessibility and recruitment, and improve the generalisability of trial‐generated evidence 2,3 . Whilst the use of decentralised trial designs is not new, the tools and approaches available to achieve these have changed dramatically since the introduction of postal‐based clinical trials in the 1980s 4,5 . This systematic review aims to summarise and evaluate published evidence on the conduct of DCTs to inform future clinical trial design.…”

Learning from remote decentralised clinical trial experiences: A qualitative analysis of interviews with trial personnel, patient representatives and other stakeholders

“…Trials without face‐to‐face interactions are not new; large, streamlined mail‐based randomised trials have been conducted since the 1980s 11–13 . Recent advances in communications technology have permitted new approaches to trial activities, such as telemedicine visits, data capture using mobile devices and online participant‐reported outcomes.…”

“…Trials without face‐to‐face interactions are not new; large, streamlined mail‐based randomised trials have been conducted since the 1980s. 11 , 12 , 13 Recent advances in communications technology have permitted new approaches to trial activities, such as telemedicine visits, data capture using mobile devices and online participant‐reported outcomes. Pfizer's REMOTE study was the first large‐scale attempt at exploiting the potential of internet‐enabled technology to run a completely web‐based trial for an investigational new drug application.…”

Medical Research Council Hot Topic workshop report: Planning a UK Nutrition and Healthy Life Expectancy Trial

“…Jane Armitage from the University of Oxford spoke about how new opportunities with digital technologies and data linkage could enhance the ability to run streamlined trials at scale with lower costs and improved quality. Giving examples from the large‐scale ORION ‐ 4 and ASCEND trials (ClinicalTrials.gov Identifier: NCT03705234; NCT00135226), she highlighted the importance of simple inclusion criteria; and the use of electronic health records to identify large numbers of participants, screen and consent them efficiently, and follow them up more completely for a wide range of events (Mafham et al, 2020).…”