Substantial discrepancies exist between registered protocol and published manuscript in trials on exercise interventions for chronic low back pain: a meta-research study

OBJECTIVES: Reporting bias, prevalent in biomedical fields, can undermine evidence credibility. Our objective was to evaluate the proportion of discrepancies between registered protocols and published manuscripts in randomized controlled trials (RCTs) on exercise interventions for patients with chronic low back pain (CLBP).

STUDY DESIGN AND SETTING: Cross-sectional meta-research study.

STUDY SELECTION: We started from the 2021 'Exercise therapy for chronic low back pain' Cochrane Review to select all RCTs reporting a protocol registration on a primary register of the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) or in ClinicalTrials.gov.

DATA EXTRACTION: We extracted data from both registered protocol and published manuscript of RCTs, collecting recruitment and administrative information (e.g., record dates) and details of trial characteristics (e.g., outcomes, arms, statistical analysis plan details). Independent pairs of reviewers assessed discrepancies between registered protocol and published manuscript for the reporting of primary and secondary outcomes domains, measurement instruments, time-points, number of arms and statistical analysis plans (if attached). Outcome discrepancies were characterized as addition, omission, upgrade or downgrade.

RESULTS: We included 116 RCTs reporting an available protocol registration. Overall, 100 RCTs (86.2%) distinguished between primary and secondary outcomes. Of these, 39 RCTs (39.0%) reported one or more discrepancies in primary outcomes, and 78 RCTs (78.0%) reported one or more discrepancies in secondary outcomes. Focusing on discrepancies for the primary outcome, 64.5% of added, upgraded or downgraded outcomes favored statistically significant effects. Few RCTs (n=6) reported discrepancies in the number of arms. Statistical analysis plans were poorly reported in the registered protocols (n=3) for being compared to the publications.

CONCLUSION: We found substantial outcome discrepancies comparing registered protocols and published manuscripts in RCTs assessing exercise interventions for patients with CLBP, with some impacting the statistical significance of the effects. Readers are encouraged to approach RCTs results in this field with caution.