Methods
Design and Study Setting
Double-blind pragmatic cluster randomised and parallel controlled study in primary care. The CONSORT-specified flow diagram and flow chart of the study design are shown in figures 1 and 2. A detailed study protocol has been published elsewhere. The study was undertaken in South-eastern Norway in 2011 and 2012.
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Figure 1.
Flow diagram of the study. BI versus BAU. BAU, business as usual; BI, brief intervention; GP, general practitioner; ICHD-II, The International Classification of Headache Disorders, Second edition; MOH, medication-overuse headache.
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Figure 2.
Flow chart of the study design. Figure illustrates main time line as well as timing of various moments for the patients, GPs and investigator group. Main outcome time point at 3 months. GP, general practitioner; MOH, medication-overuse headache.
Participants
General Practitioners. In Norway, all GP specialists participate in mandatory peer continuous medical education (CME) groups. From a list of 35 such groups within 2 h driving distance from Oslo, Norway, we invited 18 groups to a clinical training course on the management of headache in primary care.
Patients. A short headache-screening questionnaire (frequency, intensity and medication use) was posted to all 18–50-year-old patients on the 50 participating GPs' patient lists. Non-responders received two reminders.
Patients with self-reported chronic headache (≥15 days/month) and headache medication overuse ≥10 days/month, that is, self-reported MOH, were eligible for invitation to the study. Inclusion into the trial required that the diagnostic criteria of the International Classification of Headache Disorders (ICHD-II) for MOH were fulfilled after a clinical interview (Box 1). The only exclusion criterion was insufficient Norwegian language skills.
Intervention
Brief Intervention Course. The GPs received a 1-day course on headache management in the CME groups by headache specialists (CL and ESK). The course consisted of small group teaching sessions and a 2 h presentation of BI exemplified by role-play. Half of the GPs received the BI course initially, the remainder received it after the 3 months follow-up.
Brief Intervention. GPs allocated to the BI arm invited screening-positive patients with MOH to a BI consultation. SDS was scored individually during the consultation.
The five questions of the SDS adapted for headache were: (1) Do you think your use of headache medication was out of control? (never/almost never=0, sometimes=1, often=2, always/nearly always=3); (2) Did the prospect of missing a dose make you anxious or worried? (scoring as for question 1); (3) Did you worry about your use of your headache medication? (scoring as for question 1); (4) Did you wish you could stop? (scoring as for question 1); (5) How difficult would you find it to stop or go without your headache medication? (not difficult=0, quite difficult=1, very difficult=2, impossible=3).
Cut-off values of ≥5 for women at risk for MOH and ≥4 for men were used. Patients were, using a short structured scheme based on a flip-over presentation, given information about MOH and the association between medication overuse and chronic headache. Further, based on the individual SDS result, patients received feedback on their SDS score and risk of medication-induced headache. With a consultation in an empathic and collaborative manner, the BI aimed towards achieving a decision by the patient that he/she would cut down the offending medication, an agreement about how the GP could support and a concrete plan. Explicit recommendations were reduction in headache medication towards 'safe levels', and information about possible difficulties and gains including that MOH usually 'gets worse before it improves' 1–2 weeks after withdrawal. The estimated time for the BI procedure was 9 min in one single ordinary consultation. GPs allocated to the BAU arm continued business as usual.
Baseline and Follow-up Assessment
Baseline. A validated diagnostic headache diary was used to prospectively record headache frequency and intensity (VAS—Visual Analogue Scale) and medication use (figure 2). Other baseline data were collected retrospectively at the blinded 3 months follow-up (figure 2).
Follow-up. The participants were interviewed and examined 3 months after inclusion by a headache expert (ESK, KGV or CL; figure 2). The ICHD-II criteria with revisions were applied (Box 1). Patients unable to meet at the clinic were interviewed by telephone. Another 2-week headache diary was completed prior to this follow-up.
Randomisation
To avoid carry-over effects between GPs in the same CME group, the CME groups were the randomisation units, although each GP and his/her patients defined one cluster. An external statistician did the computer-generated randomisation.
Blinding
GPs were recruited, enrolled and the CME groups randomised before patients were screened and enrolled. Both GPs and patients only received information that the study aimed to evaluate headache care in general practice. There was no information about this being an intervention study in the invitation letters. All GPs and patients were blinded to study design, group participation and outcome evaluation. Investigator group (including interviewers) were blinded to patient group, intervention and treatment. The study administration collected consent forms, screening questionnaires and baseline headache diaries before any study-related contact between patient and their GP, and independently of the interviewers.
Outcomes
Outcomes were prespecified in the study protocol. Primary outcomes were numbers of headache and medication days/month comparing the two trial arms, as well as change compared with baseline. Secondary outcomes were numbers of patients at follow-up who no longer had chronic headache and medication overuse, numbers of patients with 25% and 50% reduction in headache days/month and difference in headache index (mean headache days/month×mean headache hours/day×mean pain intensity). In addition, data from headache diaries (change in headache days, medication days and VAS) were also secondary outcomes.
Sample Size
Norwegian GPs have on average 1200 listed patients. It was estimated that each GP had approximately 30–40 chronic headache patients and at least 10 patients with MOH.
Using 80% power for the detection of a difference in medication days similar to a previous study, an intraclass correlation coefficient (ICC) of 0.5 and a 5% significance level, sufficient power would have been reached with 18 patients or 5 clusters (GPs) per arm. For analyses of proportion of patients with chronic headache, calculations suggested 30 patients or 8 GPs per arm. We thus originally assumed a sample size of at least 20 GPs (100 patients assuming 5 patients per GP) to be sufficient. Since the pilot study suggested that more than three patients per GP was not feasible, we increased the number of GPs to 50 to have sufficient power on the individual patient level. If one GP had more than three screening-positive patients, a random sample of three was drawn to avoid GPs declining to participate in the study due to workload.
Statistics
Clinical characteristics were presented as frequencies or means, and SDs or 95% CIs. Differences between BI and BAU groups were assessed by χ tests for categorical variables, and independent samples t tests for continuous variables. A hierarchical linear regression model (SAS MIXED procedure) with random effects for intercepts was fitted to the continuous outcome variables to take possible correlations between members of the same cluster (GP) into account. First, crude regression coefficients were calculated by bivariate analyses. The coefficients were then adjusted for age, gender and migraine status in a multivariate model. All statistical analyses were conducted using SAS V.9.2 and SPSS V.20.0. Significance level of p<0.025 was used for the two primary outcomes (Bonferroni corrected). For all other outcomes, the level of significance was set at 5%.
Registration of data from the interviews was made using Snap Survey (Snap Survey, London, UK).
Financial Incentives
GPs earned CME credits for participating in the study. The participating patients received a free clinical examination by a headache specialist. The study covered the normal patient fee to the GP for the BI consultation.
Ethics and Data Security
Patients received written information and GPs received oral and written information before they consented. Data were anonymised and secured on a research server at Akershus University Hospital. The authors had full access to the study data.