Our search strategy identified 3381 records. After duplicates were removed, 3355 records underwent title and abstract screening. Inter-rater agreement on which studies met the criteria for full-text screening was high (raw percentage agreement 87.4%; kappa statistic 0.83, 95% CI: 0.91 to 1.00) and resulted in 2226 records being excluded. After full-text screening of the remaining 1129 records, 800 CRTs were included in our review. The study flow diagram is presented in figure 1.

Types of CRT designs included parallel arm (716, 89.5%), stepped wedge (45, 5.6%), factorial (30, 3.8%), crossover (8, 1.0%) and parallel adaptive (1, 0.1%). Clusters were most commonly geographical areas (400, 50.0%), primary care clinics or settings (167, 20.9%) and schools or classrooms (110, 13.8%). The three countries in which most CRTs were conducted were India (83, 10.4%), China (78, 9.8%) and Kenya (53, 6.6%). Table 1 presents descriptive characteristics of the 800 CRTs included in our review, online supplemental table 6 presents a full breakdown of CRT conduct by country.

Descriptive characteristics of n=800 cluster randomised trials included in the review

Among 800 CRTs, 30 (3.7%) had no authors affiliated with an institution based in an LMIC, while 124 (15.5%) were published by authors who were all affiliated with an institution based in an LMIC. First author affiliations were exclusively within high-income countries in 338 (42.2%) CRTs, exclusively with LMICs in 336 (42.0%) and both high-income country and LMIC affiliations in 126 (15.8%). Last author affiliations were exclusively with high-income countries in 410 (51.2%) CRTs, exclusively with LMICs in 303 (37.9%) and both high-income country and LMIC affiliations in 87 (10.9%). The prevalence of first and last author LMIC affiliation increases as country’s economic level increases. In 246 (30.8%) CRTs, neither first nor last author had an LMIC affiliation. Table 2 provides the descriptive summary of author affiliations.

Overview of author affiliations among n=800 cluster randomised trials included in the review

The most commonly reported primary focus among the 800 CRTs was maternal and neonatal disorders (106, 13.3%), followed by HIV/AIDS and other sexually transmitted infections (91, 11.4%) and malaria and other neglected tropical diseases (88, 11.0%). Figure 2 presents the top 10 primary foci of CRTs in LMICs. Online supplemental table 7 presents a frequency distribution of the primary focus of each CRT, including the Global Burden of Disease level 1, 2 and level 3 categories.21

Top 10 primary clinical focus of n=800 cluster randomised trials in low-income and middle-income countries.* Categories taken from the Institute for Health Metrics and Evaluation’s Global Burden of Disease 2019 Cause and Risk Summaries.

Table 3 presents information relevant to trial registration and ethics reporting. Among 800 CRTs, 670 (83.8%) reported registration in 19 different trial registries. Among the 670 CRTs reporting registration, 642 (95.8%) reported registration in one registry and 28 (4.2%) in two different registries.

Adherence to trial registration and ethics reporting requirements in n=800 cluster randomised trials included in the review

A statement about research ethics committee approval was reported in 786 (98.1%) CRTs. Of these, 452 (57.5%) reported review from both host and sponsor country, 315 (40.1%) from host country only, 18 (2.3%) from sponsor country only and 1 (0.1%) reported review from a for-profit ethics committee not associated with either the host or sponsor country.

A statement about consent was reported in 757 (94.6%) CRTs. Among studies with a consent statement, 683 (90.2%) pertained to individual-level participants (eg, patients, students), 56 (7.4%) pertained to professional-level participants (eg, health providers, teachers), 16 (2.1%) pertained to both individual-level and professional-level participants and 2 (0.3%) were unclear.

Informed consent was reported as being obtained for all aspects of the trial in 711 (93.9%) CRTs, obtained for only some aspects of the trial (eg, data collection procedures) in 20 (2.7%) and not obtained or waived for all aspects of the trial in 25 (3.3%). One (0.1%) CRT reported obtaining written informed consent from participants enrolled at three study sites, while a waiver of consent was granted at 30 study sites.

For CRTs in which consent was not obtained or waived for some or all aspects of the trial, 36 (78.3%) provided a rationale. Rationales included the use of deidentified routinely collected data, administrative data or registry data (23, 63.9%), the research involves a standard of care or usual care intervention (6, 17.7%), consent was obtained from gatekeepers (4, 11.1%), the research involves a cluster-level intervention (3, 8.3%) and other (14, 38.9%).

A gatekeeper’s role was identified in 403 (50.4%) CRTs. Identified gatekeeper roles included: assisting with study implementation or intervention development; facilitating or involved in consultations, engagement activities or public events; identifying eligible clusters or participants; providing or withholding access to data or study intervention(s); providing or withholding permission for study conduct or to approach cluster members; providing proxy consent on behalf of cluster members; and reviewing or approving study protocols.

No meaningful changes over time were observed with respect to reporting of trial registration or consent.