Finnish Degenerative Meniscal Lesion Study (FIDELITY): a protocol for a randomised, placebo surgery controlled trial on the efficacy of arthroscopic partial meniscectomy for patients with degenerative meniscus injury with a novel 'RCT within-a-cohort' study design

Raine Sihvonen, Mika Paavola, Antti Malmivaara, Teppo L N Järvinen, Raine Sihvonen, Mika Paavola, Antti Malmivaara, Teppo L N Järvinen

Abstract

Introduction: Arthroscopic partial meniscectomy (APM) to treat degenerative meniscus injury is the most common orthopaedic procedure. However, valid evidence of the efficacy of APM is lacking. Controlling for the placebo effect of any medical intervention is important, but seems particularly pertinent for the assessment of APM, as the symptoms commonly attributed to a degenerative meniscal injury (medial joint line symptoms and perceived disability) are subjective and display considerable fluctuation, and accordingly difficult to gauge objectively.

Methods and analysis: A multicentre, parallel randomised, placebo surgery controlled trial is being carried out to assess the efficacy of APM for patients from 35 to 65 years of age with a degenerative meniscus injury. Patients with degenerative medial meniscus tear and medial joint line symptoms, without clinical or radiographic osteoarthritis of the index knee, were enrolled and then randomly assigned (1 : 1) to either APM or diagnostic arthroscopy (placebo surgery). Patients are followed up for 12 months. According to the prior power calculation, 140 patients were randomised. The two randomised patient groups will be compared at 12 months with intention-to-treat analysis. To safeguard against bias, patients, healthcare providers, data collectors, data analysts, outcome adjudicators and the researchers interpreting the findings will be blind to the patients' interventions (APM/placebo). Primary outcomes are Lysholm knee score (a generic knee instrument), knee pain (using a numerical rating scale), and WOMET score (a disease-specific, health-related quality of life index). The secondary outcome is 15D (a generic quality of life instrument). Further, in one of the five centres recruiting patients for the randomised controlled trial (RCT), all patients scheduled for knee arthroscopy due to a degenerative meniscus injury are prospectively followed up using the same protocol as in the RCT to provide an external validation cohort. In this article, we present and discuss our study design, focusing particularly on the internal and external validity of our trial and the ethics of carrying out a placebo surgery controlled trial.

Ethics and dissemination: The protocol has been approved by the institutional review board of the Pirkanmaa Hospital District and the trial has been duly registered at ClinicalTrials.gov. The findings of this study will be disseminated widely through peer-reviewed publications and conference presentations.

Trial registration: ClinicalTrials.gov, number NCT00549172.

Figures

Figure 1
Figure 1
Flowchart of the efficacy trial: enrolment, assigned intervention and follow-up scheme.
Figure 2
Figure 2
(A) The diagram illustrates the randomised controlled trial (RCT) within-a-cohort study design. By prospectively following up all patients undergoing arthroscopic surgery for their degenerative meniscus injury (and not just those randomised to the efficacy RCT), we are able to obtain several distinct groups of patients with distinct prognostic factors. These groups will enable us to address several interesting hypotheses regarding the efficacy, effectiveness and cost-effectiveness of arthroscopic partial meniscectomy (APM). (B) A theoretical scheme based on Cochrane's three-step hierarchy of evidence for addressing the efficacy, effectiveness and cost-effectiveness of APM. By comparing the treatment response of groups C and D, we can address the efficacy of APM: Is the APM superior to placebo? Then, to elucidate whether our RCT truly represents a ‘best-case scenario’ (a true efficacy trial), we will assess whether the outcome of group E is superior to any subgroup of patients within the pragmatic cohort (B). If these hypotheses hold true, we can continue to ‘the second ladder of evidence’, effectiveness. We feel that the treatment response observed in the pragmatic cohort (B) should be clearly more robust than the placebo effect of APM to claim that evidence of effectiveness exists. The placebo effect of APM, in turn, can be ‘extracted’ by subtracting the difference between the groups D and C (blinded APM minus blinded placebo) from the outcome of group E (open APM), a group that should entail the combined effects of placebo and APM. Finally, if evidence of effectiveness is obtained, we can proceed to the assessment of the possible cost-effectiveness (‘cost-efficacy’—extrapolation) of APM.
Figure 3
Figure 3
A diagram outlining the follow-up scheme used in the efficacy randomised controlled trial.

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