Trial Design

We conducted this parallel-group study at five orthopedic clinics in Finland during the period from December 2007 through January 2013. Details of the trial design and methods have been published elsewhere.9 The patients, the people who collected and analyzed the data, and the authors were unaware of the study-group assignments. The protocol was approved by the institutional review board of the Pirkanmaa Hospital District. The first and last authors vouch for the accuracy and completeness of the reported data and analyses and for adherence of the study to the protocol, available with the full text of this article at NEJM.org.

The study was conducted in accordance with the Declaration of Helsinki. All patients gave written informed consent. On entering the study, patients were unequivocally informed that they might undergo sham surgery and that they would be allowed to consider crossing over to the other procedure (arthroscopic partial meniscectomy) 6 months or later after the sham procedure if they did not have adequate relief of symptoms.

Participants

Figure 1. Figure 1. Enrollment of Patients and Randomization.

We enrolled patients 35 to 65 years of age who had knee pain (for >3 months) that was unresponsive to conventional conservative treatment and had clinical findings consistent with a tear of the medial meniscus (Figure 1). Patients with an obvious traumatic onset of symptoms or with knee osteoarthritis as defined with the use of clinical criteria (American College of Rheumatology)10 or radiographic criteria (Kellgren–Lawrence grade >1)11 were excluded. On the Kellgren–Lawrence scale, grade 0 denotes no abnormalities, grade 1 minor degenerative changes (doubtful narrowing of the joint space and possible osteophytic lipping), and grade 2 knee osteoarthritis (definite narrowing of the joint line or an osteophyte). Preoperative magnetic resonance imaging (MRI) was performed to confirm the presence of a medial meniscus tear, but the eligibility of the patients was ultimately determined by arthroscopic examination. Detailed inclusion and exclusion criteria are provided in Table S1 in the Supplementary Appendix, available at NEJM.org.

Diagnostic Arthroscopy

Arthroscopic examination of the knee was first performed in all patients with the use of standard anterolateral and anteromedial portals and a 4-mm arthroscope. The orthopedic surgeon evaluated the medial, lateral, and patellofemoral joint compartments and graded the intraarticular pathologic changes (Table S2 in the Supplementary Appendix).12,13

Randomization

During the diagnostic arthroscopic procedure, if a patient was confirmed to be eligible for the trial, the surgeon asked a research nurse to open an envelope containing the study-group assignment (arthroscopic partial meniscectomy or sham surgery) and reveal it to the surgeon; the assignment was not revealed to the patient. The sequentially numbered, opaque, sealed envelopes were prepared by a statistician with no involvement in the clinical care of patients in the trial. Randomization was performed in a 1:1 ratio with a block size of 4 (known only to the statistician). The randomization sequence involved stratification according to study site, age (35 to 50 or 51 to 65 years of age), sex, and the absence or presence of minor degenerative changes on a radiograph (Kellgren–Lawrence grade 0 or 1, respectively).11 Only the orthopedic surgeon and other staff in the operating room were made aware of the group assignment, and they did not participate in further treatment or follow-up of the patient.

Operative and Postoperative Procedures

During the arthroscopic partial meniscectomy, the damaged and loose parts of the meniscus were removed with the use of arthroscopic instruments (a mechanized shaver and meniscal punches) until solid meniscal tissue was reached. The meniscus was then probed to ensure that all loose and weak fragments and unstable meniscus had been successfully resected, with preservation of as much of the meniscus as possible. No other surgical procedure was performed.

For the sham surgery, a standard arthroscopic partial meniscectomy was simulated. To mimic the sensations and sounds of a true arthroscopic partial meniscectomy, the surgeon asked for all instruments, manipulated the knee as if an arthroscopic partial meniscectomy was being performed, pushed a mechanized shaver (without the blade) firmly against the patella (outside the knee), and used suction. The patient was also kept in the operating room for the amount of time required to perform an actual arthroscopic partial meniscectomy.

No medication was instilled into the knee during arthroscopy. All procedures were standardized and recorded on video. In both the partial-meniscectomy group and the sham-surgery group, postoperative care was delivered according to a standardized protocol specifying that all patients receive the same walking aids and instructions for the same graduated exercise program (Fig. S1 in the Supplementary Appendix). Patients were instructed to take over-the-counter analgesic agents as required.

Outcome Measures

Initially, our two primary outcomes were knee pain after exercise (during the preceding week) and the Lysholm knee score at 12 months after surgery. Knee pain was assessed on an 11-point scale ranging from 0 (no pain) to 10 (extreme pain). The Lysholm knee score is a validated,14 condition-specific outcome measure.15 After the Western Ontario Meniscal Evaluation Tool (WOMET),16 a meniscus-specific health-related quality-of-life instrument, was validated for patients with a degenerative meniscal tear,17 this measure was added as our third primary outcome (before any data analysis). The Lysholm and WOMET scores each range from 0 to 100, with 0 indicating the most severe symptoms and 100 an absence of symptoms. Secondary outcomes included the score for knee pain after exercise and the Lysholm and WOMET score measured at 2 and 6 months after surgery; knee pain at rest, measured at 12 months; and the score on 15D, a generic health-related quality-of-life instrument made up of 15 dimensions and scored on a scale of 0 (death) to 1 (full health), also measured at 12 months.18

Questionnaires were administered at baseline and at 2, 6, and 12 months after surgery. The follow-up questionnaires included a separate section on adverse events, defined as untoward medical occurrences that may or may not have had a causal relationship with the treatment administered. Adverse events were classified as serious if they necessitated hospitalization or prolonged inpatient hospital care, or if they were life-threatening or resulted in death. For the 12-month follow-up questionnaire, the patients also responded to the following four questions: Is your knee better than before the intervention? Are you satisfied with your knee at present? Would you choose to be operated on again if you were asked to make the decision now? Which procedure do you think you underwent? Responses to the first two questions were given on a 5-point Likert scale; the response to the third question was “yes” or “no.”

Statistical Analysis

We powered the study to detect a minimal clinically important improvement in the Lysholm and WOMET scores (improvements of at least 11.5 and 15.5 points, respectively) and in the score for knee pain after exercise (improvement of at least 2.0 points) between the partial-meniscectomy and sham-surgery groups.9 The estimates of minimal clinically important improvement were based on the difference we noted in our prospective cohort of 377 patients with a degenerative meniscal injury who had undergone arthroscopic partial meniscectomy.9 For the study to have 80% power to show a clinically meaningful advantage of arthroscopic partial meniscectomy over sham surgery, under the assumption of a two-sided type 1 error rate of 5%, the required sample sizes were 40, 54, and 40 participants per group for the Lysholm score, the WOMET score, and the score for knee pain after exercise, respectively. Anticipating a loss to follow-up of at least 20%, we planned to recruit 70 patients per group.

The trial was designed to ascertain whether arthroscopic partial meniscectomy is superior to sham surgery, at 12 months after the procedure, with regard to the three primary outcomes. Baseline characteristics were analyzed with the use of descriptive statistics. For the primary analysis, the change in each score (mean and 95% confidence interval) from baseline to 12 months was compared between the two study groups. This analysis was also performed after adjustment for the baseline score and for the stratifying variables used for randomization. Secondary analyses included between-group comparisons of the change in the 15D score and in the score for knee pain at rest, as well as comparisons of the frequencies of patients who reported satisfaction or subjective improvement, who had serious adverse events, or whose treatment assignment was revealed within 12 months after surgery (who required subsequent knee surgery). Analyses of the primary outcomes were also performed at 2 and 6 months, but these analyses were intended only to illustrate the trajectory of the treatment response.

Because knee osteoarthritis has been associated with poor outcomes after knee arthroscopy,19 our only prespecified subgroup analysis was performed with patients stratified according to the extent of radiographically assessed degenerative changes (Kellgren–Lawrence grade 0 [no degeneration] vs. grade 1 [minor degenerative changes]). A Student's t-test and nonparametric test were used to compare continuous variables (normally distributed and not normally distributed, respectively) between the groups, and Fisher's exact test was used with binomial and categorical variables. Univariate analysis was used to test for interaction in the subgroup analysis. All statistical analyses were performed on an intention-to-treat basis; no per-protocol analysis was performed, because the frequency of crossover was low. A P value of 0.05 was considered to indicate statistical significance. SPSS Statistics, version 20 (IBM), was used for all statistical analyses.

The writing committee developed and recorded two interpretations of the results on the basis of a blinded review of the primary outcome data (treatment A compared with treatment B), one assuming that treatment A was arthroscopic partial meniscectomy, and the other assuming that treatment A was sham surgery. Only after the committee members had agreed that there would be no further changes in the interpretation was the randomization code broken, the correct interpretation chosen, and the manuscript finalized (see the Supplementary Appendix).20