The Publications Book
The Heidari Publications
94 publications · 23 years of research · click or drag a page corner to turn
Royal College
British Orthopaedic
AO Trauma
Churchill
Limb Recon
Specialist Reg.
Schlüssel MM, Keene DJ, Wagland S, Alsousou J, Lamb SE, Willett K, et al..
BackgroundThere has been a recent steep growth in platelet-rich plasma (PRP) use for musculoskeletal conditions, but findings from high quality clinical trial data are lacking in the literature. Here, we describe the statistical analysis plan (SAP) for the Platelet-rich plasma in Achilles Tendon Healing 2 (PATH-2) trial.MethodsPATH-2 is a pragmatic, parallel-group, multi-centre, double-blinded, randomised, placebo-controlled, superiority trial. The study aims to evaluate the clinical efficacy of PRP in acute Achilles tendon rupture in terms of muscle-tendon function. Patients are identified in the orthopaedic/trauma outpatient clinic. The primary outcome is muscle-tendon work capacity from the Heel Rise Endurance Test result, expressed as the Limb Symmetry Index (work, in joules), at 24 weeks post randomisation. Multivariate linear regression adjusting for the stratification factors (centre and age) and additional prognostic factors will be used to investigate the adjusted effect of the intervention. The analysis will be by modified intention-to-treat. Sensitivity analysis will assess the internal validity of the trial results by performing a per-protocol analysis. Safety will be summarised by treatment arm for all patients who started treatment. Secondary patient-reported outcome measures will be analysed using linear mixed effects models to allow all data collected at all follow-up points to be considered. Missing data will be summarised and reported by treatment arm. Missing data imputation will be performed, if appropriate.DiscussionThe PATH-2 trial will be reported in accordance with the CONSORT statement. This SAP publication will avoid bias arising from prior knowledge of the study results. Any changes or deviations from the current SAP will be described and justified in the final report.Trial registrationISRCTN registry: ISRCTN54992179 , assigned 12 January 2015. ClinicalTrials.gov: NCT02302664, received 18 November 2014. UK Clinical Research Network Study Portfolio Database: ID 17850.
What did we look at?
The pre-agreed statistical plan for the PATH-2 trial — a multi-centre, double-blinded, randomised study testing whether platelet-rich plasma (PRP) injections help acute Achilles tendon ruptures heal better than placebo.
Why did we look at it?
PRP has become widely used for tendon and muscle injuries, but it has been adopted faster than the high-quality trial evidence to support it. Publishing a statistical analysis plan before the results are known is good scientific practice: it locks in how the data will be analysed, so the team cannot be accused of choosing the analysis after seeing the answer they want.
What did we find?
The plan describes how the main outcome — calf-muscle work measured by a heel-rise endurance test at 24 weeks — will be compared between the PRP and placebo groups. It defines secondary patient-reported outcomes, how missing data will be handled, and how safety will be reported. Crucially, this paper does not report any results: it is published before the data are unblinded.
What does this mean for patients?
Patients can have more confidence in trial findings when the analysis was pre-specified. The PATH-2 trial itself, when reported, will give a clearer answer on whether PRP genuinely helps Achilles ruptures recover — an answer that has been overdue for the orthopaedic community.
Trials 2018;19(1):464. doi:10.1186/s13063-018-2840-z