Although over 90% of patient contacts within the NHS occur in primary care, many of the interventions used in this setting remain unproved.1 The relevance of research undertaken in secondary or tertiary care to general practice is questionable, and more research based in primary care is needed.2 Increasing research in primary care will inevitably increase demand for randomised controlled trials in this setting. Some of the trials will be of health service interventions (pragmatic trials),3 where the focus lies in assessing the cost effectiveness of an intervention rather than efficacy or safety. The difficulties experienced in doing randomised controlled trials in primary care have been reported4–6 and are not restricted to this setting.7,8 We discuss some of the issues that must be considered when conducting and interpreting the results of trials in primary care using examples generated during a trial of the management of dyspepsia (box).
Birmingham open access endoscopy study
The study aimed to evaluate the effectiveness of two management strategies for patients presenting in primary care with symptoms of dyspepsia. Two randomised controlled trials were conducted concurrently, with eligibility being determined by the patient's age at presentation. Randomisation was done at the individual patient level by using sealed opaque, sequentially numbered envelopes during a primary care consultation for dyspepsia.
Initial endoscopy trial
Eligible patients—50 years of age or older.
Intervention—Referred for open access endoscopy.
Test and endoscopy trial
Eligible patients—Under 50 years.
Intervention—Tested for Helicobacter pylori antibodies with Helisal near patient test. Patients with positive results referred for open access endoscopy; those with negative results received symptomatic treatment only.
Control arms (both trials)—Managed according to “usual practice” excluding open access endoscopy. This included antacids, H2 receptor antagonists, proton pump inhibitors, outpatient gastroenterology referral, facilitated or direct access endoscopy (for example, vetted by consultant), and testing for H pylori.
Outcomes—Primary outcomes were change in symptom score and cost effectiveness. Secondary outcomes included quality of life and acceptability.
Data collection—At recruitment, general practitioners completed a case report form providing patient identifiers and a limited amount of baseline data. Patients completed the dyspepsia symptom questionnaire and the quality of life questionnaire at recruitment and at six and 18 months after randomisation. A patient satisfaction questionnaire was also completed at 18 months. Data on use of health services were collected from general practice records and endoscopy units at 12 months after recruitment.
- All trials require a compromise between including sufficient practitioners to recruit a representative cohort of patients and the time and cost of recruiting and maintaining the motivation of these practitioners
- Prior beliefs relating to the efficacy and direct or side effects of an intervention affect both doctor and patient participation
- Trials in any setting are rarely fully representative with respect to both patient and disease related characteristics
- Modelling, sensitivity analysis, and statistical estimates of uncertainty are necessary to determine the generalisability of trials and to particularise results to a given clinical setting
- Trials in primary care should give more representative results and are preferable to applying results obtained in secondary care
Dyspepsia is a common clinical problem. About 2% of the population consult their general practitioner each year with dyspeptic symptoms,9 and it costs the NHS more than £1bn a year, with a large proportion of these costs relating to drug prescription.10 The evidence base has largely consisted of cohort studies of patients referred to secondary care for investigation11,12and economic models.13 In the absence of evidence from primary care, several conflicting consensus guidelines have been generated.14,15 Dyspepsia represents a good example of a chronic disease that is largely managed in primary care and that requires high quality evidence from randomised controlled trials in primary care.