Registration and reporting characteristics of trials investigating exercise therapy following total knee arthroplasty: a systematic review.

Clinical Snapshot

Key Findings

• P Value: Not explicitly reported in abstract; the CI for prospectively registered trials crosses zero, indicating non-significance

• Effect Size: Prospectively registered: SMD 0.06; Retrospectively registered: SMD 0.67; Unregistered: SMD 0.59

• Primary Outcome: Pooled standardised mean difference (SMD) of primary outcomes stratified by trial registration status, with prospectively registered trials showing markedly smaller effect sizes than retrospectively registered or unregistered trials

• Nnt Or Sensitivity: Not applicable (methodological systematic review); however, the difference in SMD between prospectively registered (0.06) and non-prospectively registered trials (0.59–0.67) represents a clinically meaningful inflation of approximately 0.53–0.61 SMD units attributable to selective outcome reporting — equivalent to moving from a negligible to a moderate-to-large effect by Cohen's conventions

• Confidence Interval: Prospectively registered: 95% CI −0.03 to 0.16; Retrospectively registered: 95% CI 0.22 to 1.11; Unregistered: 95% CI 0.32 to 0.86

Clinical Application

The findings do not directly change exercise prescription but should substantially alter how clinicians and guideline bodies weight evidence from non-prospectively registered trials. Clinicians should seek out prospectively registered trials when evaluating exercise interventions and apply greater scepticism to effect size estimates from unregistered or retrospectively registered studies. In Australia, TKA is one of the most commonly performed elective orthopaedic procedures, with over 60,000 procedures performed annually. Post-TKA rehabilitation is a standard component of care, typically involving physiotherapy-led exercise programs. The RACGP and Australian Physiotherapy Association (APA) clinical guidelines for post-TKA rehabilitation draw heavily on RCT evidence — the finding that the majority of this evidence base is unregistered or retrospectively registered, with inflated effect sizes, has direct implications for Australian guideline development. The TGA does not regulate exercise therapy, but the MBS funds post-TKA physiotherapy services; evidence quality directly informs funding decisions. Australian researchers conducting TKA rehabilitation trials should ensure prospective registration on ANZCTR (Australian New Zealand Clinical Trials Registry) prior to participant enrolment, consistent with NHMRC and ICMJE requirements. Clinicians, guideline developers, systematic reviewers, and researchers working in post-TKA rehabilitation; findings are directly relevant to any clinician interpreting the exercise therapy literature for TKA patients

Abstract

BACKGROUND AND PURPOSE: Prospectively registering the primary trial outcome is important to reduce selective outcome reporting and increase the trustworthiness of findings, which guide clinical practice. The objectives of our systematic review were to explore and compare the reporting characteristics of prospectively and non-prospectively registered trials investigating exercise therapy following total knee arthroplasty. METHODS: Randomized trials comparing effects of exercise therapy after total knee arthroplasty for osteoarthritis were identified in 4 databases from 2000 to August 12, 2024. One primary outcome per trial was extracted, using a pre-specified hierarchical algorithm, irrespective of outcome domain. Pooled standardized mean differences (SMDs) were calculated on pre-specified outcome domains, and risk-of-bias assessed using the Cochrane Risk-of-Bias tool v2. RESULTS: 94 trials, comprising 9,396 participants, were included, of which 13 were prospectively registered, 33 retrospectively registered, and 48 unregistered. A single primary outcome was defined in 44% of the 94 trials, and 4 trials reported a primary outcome consistent with a prospective registration. The pooled SMD of primary outcomes was 0.06 (95% confidence interval [CI] -0.03 to 0.16) for prospectively registered trials, 0.67 (CI 0.22-1.11) for retrospectively registered trials, and 0.59 (CI 0.32-0.86) for unregistered trials. Lower risk-of-bias ratings and higher proportions of intention-to-treat adherence, dropout reporting, and adverse event reporting were observed among prospectively registered trials. CONCLUSION: Among prospectively registered trials we showed smaller effect size estimates between interventions with lower risk-of-bias ratings, and higher proportions of intention-to-treat adherence, dropout reporting, and adverse event reporting in contrast to trials without prospective registration; furthermore, clear specification of a single primary outcome was uncommon among trials evaluating exercise therapy after total knee arthroplasty.

References

1. 1.Grønfeldt, B. M., Husted, R. S., Brødsgaard, R. H., Holst, L., Kallemose, T., Chapple, C. M., Juhl, C. B., & Bandholm, T. (2026). Registration and reporting characteristics of trials investigating exercise therapy following total knee arthroplasty: a systematic review. Acta Orthopaedica. https://doi.org/10.2340/17453674.2026.46047