We conducted a randomized, controlled, parallel-group trial in a tertiary care ear, nose and throat centre. All patients provided written informed consent. The study protocol was approved by the Oulu University Hospital ethics committee.
We selected participants from consecutive patients referred for tonsillectomy because of recurrent pharyngitis from Oct. 29, 2007, to June 30, 2010.
The clinical criterion for entry to the study was 3 or more episodes of pharyngitis within the previous 12 months. These episodes had to be disabling, prevent normal functioning, be severe enough for the patient to seek medical attention and be thought to involve the palatine tonsils. It was not necessary for culture or antigen tests to have shown infection with group A streptococcus. Our exclusion criteria were age less than 13 years, history of peritonsillar abscess, chronic tonsillitis, ongoing use of antibiotic agents, residence outside of the Oulu region, pregnancy or previous illness making same-day surgery unfeasible.
We assigned patients to the control group or the tonsillectomy group using simple randomization. The allocation sequence was concealed from the investigators using sequentially numbered, opaque, sealed envelopes (Appendix 1, available at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.121852/-/DC1
The patients in the control group were placed on a waiting list for tonsillectomy to undergo surgery after 5 to 6 months (watchful waiting); patients in the tonsillectomy group underwent surgery as soon as possible. Surgery involved total extracapsular removal of both palatine tonsils under general anesthesia. For practical reasons, the median time between the randomization to the tonsillectomy group and surgery was 14 (interquartile range 8–23) days.
Upon assignment to one of the study groups, patients underwent examination, and we collected background data. Both groups were scheduled to be followed for at least 5 months after randomization.
We advised the patients to visit the study physician or their general practitioner whenever they had acute symptoms suggestive of pharyngitis. In addition, we told patients that it was important to seek medical advice for their symptoms during the trial exactly as they had done before. At the acute visit, patients underwent a thorough clinical examination including a throat swab6
and a blood test to measure serum levels of C-reactive protein (Appendix 1). The blood test was repeated 3 days later. All laboratory and microbiological analyses were performed by staff blinded to the clinical data.
A study notebook provided to the patients included information about the study and written instructions for their general practitioners, which included information on examining and recording ear, throat and nose status and taking blood samples and throat cultures (Appendix 1). Patients received treatment as prescribed by a physician (the study physician if available), who recorded the date, location, diagnosis and treatment of acute episodes in the notebook. For patients in the tonsillectomy group, the study notebook also included a Glasgow Benefit Inventory health-related quality-of-life questionnaire7
to be answered 6 months after surgery. This instrument has been validated in Finnish by translation, reconciliation, back-translation and pilot testing.8
The patients used a symptom diary to record the presence and severity (mild, moderate or severe) of the following acute symptoms: throat pain, cough, rhinitis, fever and absence from school or work. Symptoms lasting more than 30 days were considered chronic and were not included in our analysis.
We collected the study notebooks at the follow-up visit. We checked missing or unreadable information by telephone. We recorded data concerning acute visits and tonsillectomy from patients’ charts.
Our primary outcome was the difference in the proportion of patients who had a severe episode of pharyngitis within 5 months. A severe episode had to involve medical consultation registered in the study notebook, and the patient needed to have acute throat pain and signs suggesting the symptoms originated in the pharynx (e.g., edema, erythema, exudative tonsillitis, anterior cervical lymphadenitis). In addition, the serum level of C-reactive protein either on the day of the appointment or 3 days later had to be higher than 40 mg/L.9
If a blood sample was not taken, the result of a throat culture had to show other than normal flora, and the patient had to grade the throat pain as severe. Secondary outcomes were differences in proportions of patients with any episode of pharyngitis (sore throat lasting ≥ 2 d) and episodes with medical consultation during the 5-month follow-up, times to pharyngitis episodes, the difference in the mean rates of episodes, the mean number of days absent from school or work and the mean number of symptomatic days during follow-up. We also recorded health-related quality of life and adverse effects related to tonsillectomy.
We estimated that 70 patients needed to be enrolled in the study for it to have statistical power of 80% to detect an absolute difference of 25% in the recurrence rates of severe pharyngitis. We determined this estimate using a 5-month recurrence rate of 25% in the control group and 0% in the tonsillectomy group based on the results of the previous trial by Alho and colleagues.3
We considered a 2-sided p
value of 0.05 to be significant. We analyzed all of the participants on an intention-to-treat basis according to a pre-established plan.
For descriptive data, we calculated means with standard deviations or medians with interquartile ranges. We used the Mann–Whitney U test to compare continuous variables. We constructed survival curves, as they related to the treatment group, using the Kaplan–Meier method, starting from the date of randomization in the control group and from the date of surgery in the tonsillectomy group. We tested differences between the groups using the log-rank test. We calculated the absolute difference and the 95% confidence intervals (CIs) in the proportions of recurrence between the groups at 5 months.
We determined the number of all episodes of pharyngitis, symptomatic days and absences from school or work per person-year using data obtained during follow-up. However, in the tonsillectomy group, we excluded from the risk time the individual recovery times immediately after tonsillectomy during which the patient had continuous throat pain (mean 17 ± 6 d). In scoring the Glasgow Benefit Inventory questionnaire, we averaged the responses to all 18 questions to give each question equal weight. We then transposed the average score onto a continual benefit scale ranging from −100 to 100; a score of −100 meant maximal harm, a score of 0 meant no change, and a score of 100 suggested maximal benefit to quality of life.