Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2018

Open Access 01-12-2018 | Review

Post-trial follow-up methodology in large randomised controlled trials: a systematic review

Authors: Rebecca Llewellyn-Bennett, Danielle Edwards, Nia Roberts, Atticus H. Hainsworth, Richard Bulbulia, Louise Bowman

Published in: Trials | Issue 1/2018

Login to get access

Abstract

Background

Randomised controlled clinical trials typically have a relatively brief in-trial follow-up period which can underestimate safety signals and fail to detect long-term hazards, which may take years to appear. Extended follow-up after the scheduled closure of the trial allows detection of both persistent or enhanced beneficial effects following cessation of study treatment (i.e. a legacy effect) and the emergence of possible adverse effects (e.g. development of cancer).

Methods

A systematic review was conducted following PRISMA guidelines to qualitatively compare post-trial follow-up methods used in large randomised controlled trials. Five bibliographic databases, including Medline and the Cochrane Library, and one trial registry were searched. All large randomised controlled trials (more than 1000 adult participants) published from March 2006 to April 2017 were evaluated. Two reviewers screened and extracted data attaining > 95% concordance of papers checked. Assessment of bias in the trials was evaluated using the Cochrane Risk of Bias tool.

Results

Fifty-seven thousand three hundred and fifty-two papers were identified and 65 trials which had post-trial follow-up (PTFU) were included in the analysis. The majority of trials used more than one type of follow-up. There was no evidence of an association between the retention rates of participants in the PTFU period and the type of follow-up used. Costs of PTFU varied widely with data linkage being the most economical. It was not possible to assess associations between risk of bias during the in-trial period and proportions lost to follow-up during the PTFU period.

Discussion

Data captured during the post-trial follow-up period can add scientific value to a trial. However, there are logistical and financial barriers to overcome. Where available, data linkage via electronic registries and records is a cost-effective method which can provide data on a range of endpoints.

Systematic review registration

Not applicable for PROSPERO registration.
Appendix
Available only for authorised users
Literature
1.
Ford I., et al., Long-term safety and efficacy of lowering low-density lipoprotein cholesterol with statin therapy: 20-year follow-up of West of Scotland Coronary Prevention Study. (1524–4539 (Electronic)).
2.
Heart Protection Study Collaborative Group, et al. Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20,536 high-risk individuals: a randomised controlled trial. Lancet. 2011;378(9808):2013–20.CrossRefPubMedPubMedCentral
3.
4.
Brueton VC, et al., Strategies to improve retention in randomised trials: a Cochrane systematic review and meta-analysis. (2044–6055 (Linking)).
5.
Barton J, Young A, Lay M., Introduction of electronic data capture method using participant-completed online web-based follow up questionnaire in mail-based study achieves expected benefits and positive participant feedback. Trials, 2015. 16(2): p44.
6.
Scuffham P, Chaplin S, Legood R. Incidence and costs of unintentional falls in older people in the United Kingdom. J Epidemiol Community Health, 2003. 57(9): p. 740.
7.
Llewellyn-Bennett R, Bowman L, Bulbulia R Post-trial follow-up methodology in large randomized controlled trials: a systematic review protocol. Systematic Reviews, 2016. 5: p. 214.
8.
9.
10.
Arber N, et al. Five-year analysis of the prevention of colorectal sporadic adenomatous polyps trial. Am J Gastroenterol. 2011;106(6):1135–46.CrossRefPubMed
11.
Margolis KL, et al. Long-term follow-up of moderately hypercholesterolemic hypertensive patients following randomization to pravastatin vs usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). J Clin Hypertens (Greenwich). 2013;15(8):542–54. (1751–7176 (Electronic)).
12.
13.
Lloyd SM, et al. Long-term effects of statin treatment in elderly people: extended follow-up of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). PLoS ONE [Electronic Resource]. 2013;8(9):e72642.CrossRef
14.
Kivimaki M, et al. Validity of cardiovascular disease event ascertainment using linkage to UK hospital records. Epidemiology. 2017;28(5):735–9.
15.
16.
Metadata
Title
Post-trial follow-up methodology in large randomised controlled trials: a systematic review
Authors
Rebecca Llewellyn-Bennett
Danielle Edwards
Nia Roberts
Atticus H. Hainsworth
Richard Bulbulia
Louise Bowman
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Trials / Issue 1/2018
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-018-2653-0

Other articles of this Issue 1/2018

Trials 1/2018 Go to the issue

Study protocol

Mechanisms and modulators of cognitive training gain transfer in cognitively healthy aging: study protocol of the AgeGain study

Study protocol

The CIRCuiTS study (Implementation of cognitive remediation in early intervention services): protocol for a randomised controlled trial

Study protocol

Danggwijagyaksan for climacteric syndrome in peri- and postmenopausal women with a blood-deficiency dominant pattern: study protocol for a randomized, double-blind, placebo-controlled pilot trial

Study protocol

Leucine and ACE inhibitors as therapies for sarcopenia (LACE trial): study protocol for a randomised controlled trial

Study protocol

Open-label, randomized multicentre phase II study to assess the efficacy and tolerability of sunitinib by dose administration regimen (dose modification or dose interruptions) in patients with advanced or metastatic renal cell carcinoma: study protocol of the SURF trial

Study protocol

Culturally tailored, peer-based sleep health education and social support to increase obstructive sleep apnea assessment and treatment adherence among a community sample of blacks: study protocol for a randomized controlled trial