Informed consent in pragmatic trials: results from a survey of trials published 2014-2019.

OBJECTIVES: To describe reporting of informed consent in pragmatic trials, justifications for waivers of consent and reporting of alternative approaches to standard written consent. To identify factors associated with (1) not reporting and (2) not obtaining consent. METHODS: Survey of primary trial reports, published 2014-2019, identified using an electronic search filter for pragmatic trials implemented in MEDLINE, and registered in ClinicalTrials.gov. RESULTS: Among 1988 trials, 132 (6.6%) did not include a statement about participant consent, 1691 (85.0%) reported consent had been obtained, 139 (7.0%) reported a waiver and 26 (1.3%) reported consent for one aspect (eg, data collection) but a waiver for another (eg, intervention). Of the 165 trials reporting a waiver, 76 (46.1%) provided a justification. Few (53, 2.9%) explicitly reported use of alternative approaches to consent. In multivariable logistic regression analyses, lower journal impact factor (p=0.001) and cluster randomisation (p<0.0001) were significantly associated with not reporting on consent, while trial recency, cluster randomisation, higher-income country settings, health services research and explicit labelling as pragmatic were significantly associated with not obtaining consent (all p<0.0001). DISCUSSION: Not obtaining consent seems to be increasing and is associated with the use of cluster randomisation and pragmatic aims, but neither cluster randomisation nor pragmatism are currently accepted justifications for waivers of consent. Rather than considering either standard written informed consent or waivers of consent, researchers and research ethics committees could consider alternative consent approaches that may facilitate the conduct of pragmatic trials while preserving patient autonomy and the public's trust in research.

Smoking cessation in individuals who use vaping as compared with traditional nicotine replacement therapies: a systematic review and meta-analysis.

OBJECTIVES: Despite the aggressive marketing of electronic nicotine device systems (ENDS) as smoking cessation tools, the evidence of their effectiveness is mixed. We conducted a systematic review of randomised controlled trials to determine the effect of ENDS on cigarette smoking cessation, as compared with other types of nicotine replacement therapies (NRT). DESIGN: Systematic review and meta-analysis using the Grading of Recommendations Assessment, Development and Evaluation approach. DATA SOURCES: MEDLINE, Embase, the CENTRAL Trials Registry of the Cochrane Collaboration using the Ovid interface, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform trials registries were searched through 17 June 2020. ELIGIBILITY CRITERIA FOR STUDIES: Randomised controlled trials in which any type of ENDS was compared with any type of NRT, in traditional cigarette users. DATA EXTRACTION AND SYNTHESIS: The primary outcome was smoking cessation, defined as abstinence from traditional cigarette smoking for any time period, as reported in each included study, regardless of whether abstinence is self-reported or biochemically validated. Secondary outcomes included smoking reduction, harms, withdrawal and acceptance of therapy. A random-effect model was used, and data were pooled in meta-analyses where appropriate. RESULTS: Six studies were retained from 270. Most outcomes were judged to be at high risk of bias. The overall quality of evidence was graded as 'low' or 'very low'. Pooled results showed no difference in smoking cessation (rate ratio (RR) 1.42, 95% CI 0.97 to 2.09), proportion of participants reducing smoking consumption (RR 1.25, 95% CI 0.79 to 1.98), mean reduction in cigarettes smoked per day (mean difference 1.11, 95% CI -0.41 to 2.63), or harms (RR 0.96, 95% CI 0.76 to 1.20), between groups. CONCLUSION: We found no difference in smoking cessation, harms and smoking reduction between e-cigarette and NRT users. However, the quality of the evidence was low. Further research is needed before widespread recommendations are made with regard to the use of ENDS. PROSPERO REGISTRATION NUMBER: Systematic review registration number: protocol registered with the International Prospective Register of Systematic Reviews (PROSPERO) on February 27th, 2020; CRD42020169416.

A review of pragmatic trials found a high degree of diversity in design and scope, deficiencies in reporting and trial registry data, and poor indexing.

OBJECTIVE: We established a large database of trials to serve as a resource for future methodological and ethical analyses. Here, we use meta-data to describe the broad landscape of pragmatic trials including research areas, identification as pragmatic, quality of trial registry data and enrolment. STUDY DESIGN AND SETTING: Trials were identified by a validated search filter and included if a primary report of a health-related randomized trial published January 2014-April 2019. Data were collated from MEDLINE, Web of Science, ClinicalTrials.gov, and full text. RESULTS: 4337 eligible trials were identified from 13,065 records, of which 1988 were registered in ClinicalTrials.gov. Research areas were diverse, with the most common being general and internal medicine; public, environmental and occupational health; and health care sciences and services. The term "pragmatic" was seldom used in titles or abstracts. Several domains in ClinicalTrials.gov had questionable data quality. We estimated that one-fifth of trials under-accrued by at least 15%. CONCLUSION: There is a need to improve reporting of pragmatic trials and quality of trial registry data. Under accrual remains a challenge in pragmatic RCTs despite calls for more streamlined recruitment approaches. The diversity of pragmatic trials should be reflected in future ethical analyses.