A randomized database study in general practice yielded quality data but patient recruitment in routine consultation was not practical.

OBJECTIVE: To assess patient recruitment and quality of data in a randomized database study. STUDY DESIGN AND SETTING: A randomized database study was conducted in the Integrated Primary Care Information (IPCI) general practice research database. Software was built to allow for automated patient identification and recruitment, and randomization. As an application, we compared gastrointestinal tolerability in persons treated with diclofenac and celecoxib for osteoarthritis. The outcomes were assessed in the IPCI database. To assess accuracy of exposure and outcome, we also collected information by self-administrated patient questionnaires. For all eligible subjects, we assessed the main reason for noninclusion. Physicians were interviewed to evaluate the study and to identify the major obstacles. RESULTS: Forty-two general practice physicians collaborated with the study and 7,127 potential study subjects were identified. Among these subjects, 170 were eligible for recruitment and 20 (11.8%) were randomized. Of the eligible patients, 96 (56.5%) were not recruited because the physician was too busy or the patient was treated by another healthcare provider and 54 (31.8%) were not recruited because of exclusion criteria. CONCLUSION: Concordance between questionnaires and IPCI data and the outcome was good (kappa=0.7; SD=0.14). The physicians reported that recruitment during routine visits was too time-consuming, in particular because of the need for informed consent. Although a randomized database study is feasible, patient recruitment during routine consultations should be avoided.

A technical infrastructure to conduct randomized database studies facilitated by a general practice research database.

General practice research databases are increasingly used to study intended and unintended effects of treatments. However, confounding by indication remains a major problem. The randomized database study methodology has been proposed as a method to combine the strengths of observational database (generalizability) and the strength of the randomized clinical trial (RCT) design (randomization). We developed an infrastructure that enables the execution of randomized database studies with treatment randomization facilitated by a general practice research database. The requirements posed by the methodology of randomized database studies were facilitated by software components. Our assessment showed that it is technically possible to conduct randomized trials in general practice according to the randomized database design. The infrastructure facilitated the conduct of randomized database studies in general practice but some practical difficulties and methodological issues remain. The technical infrastructure seems to be both promising and potentially feasible to facilitate future randomized database studies, although the methodology needs to be evaluated in more detail.

Randomised studies in general practice: how to integrate the electronic patient record.

The 'randomised database study' strategy was first proposed in 1997, with the aim of combining the generalisability of observational database studies based on electronic patient records (EPRs) with the validity of randomised clinical trials (RCTs). The key feature was to randomly assign treatments and to use routine care data, as available in the observational database, for patient identification and follow-up. To our knowledge, however, the idea of the randomised database study has not been implemented yet. The conduct of a randomised study in an observational database requires adjustments to methods of medical information processing in the general practice. We developed a software system that facilitates the conduct of an RCT with observational databases based on EPRs. It identifies eligible subjects and presents them one by one to the physician once their EPR is accessed. The general practitioner can then start an interactive recruitment process; after completion, the computer randomises the patients. Follow-up is documented by normal routine care in the EPR. Although the randomised database study has many methodological advantages, it has never been tested. Our software system is meant as a tool to implement and facilitate evaluation of the randomised database approach.

Spironolactone and risk of upper gastrointestinal events: population based case-control study.

OBJECTIVE: To confirm and quantify any association between spironolactone and upper gastrointestinal bleeding and ulcers. DESIGN: Population based case-control study. SETTING: A primary care information database in the Netherlands. PARTICIPANTS: All people on the database who were aged 18 or more between 1 January 1996 and 30 September 2003. Patients with a history of alcoholism or gastrointestinal cancer were excluded. Ten controls were matched to each case of gastroduodenal ulcer or upper gastrointestinal bleeding by age (year of birth), sex, and index date. MAIN OUTCOME MEASURES: The occurrence of an upper gastrointestinal event (bleeding or ulcers), adjusted for potential confounders with conditional logistic regression analysis. RESULTS: Within the source population of 306 645 patients, 523 cases of gastric or duodenal ulcer or upper gastrointestinal bleeding were identified and matched to 5230 controls. Current use of spironolactone was associated with a 2.7-fold (95% confidence interval 1.2 to 6.0) increased risk of a gastrointestinal event. CONCLUSION: The risk of gastroduodenal ulcers or upper gastrointestinal bleeding is significantly increased in patients using spironolactone.

Channeling and prevalence of cardiovascular contraindications in users of cyclooxygenase 2 selective nonsteroidal antiinflammatory drugs.

OBJECTIVE: To assess use and channeling of cyclooxygenase 2 selective inhibitors (coxibs) over time and to estimate the percentage of coxib users with cardiovascular contraindications. METHODS: The study population comprised all coxib and nonselective nonsteroidal antiinflammatory drug (NSAID) users in the Integrated Primary Care Information project between January 2000 and December 2004. The prevalence of risk factors for NSAID-related upper gastrointestinal ulcer complications, cardiovascular disease, and cerebrovascular disease at the start of treatment was compared between users of coxibs and users of nonselective NSAIDs. RESULTS: The study population included 72,841 nonselective NSAID users and 10,739 coxib users. The prevalence of risk factors for NSAID-related gastrointestinal complications was higher in coxib users than nonselective NSAID users (odds ratio [OR] 1.18, 95% confidence interval [95% CI] 1.10-1.26). Similarly, the prevalence of prior cardiovascular disease was higher in coxib users than in nonselective NSAID users (OR 1.35, 95% CI 1.28-1.43). Channeling of coxibs to patients with NSAID-related gastrointestinal risk factors declined after 2001 but increased again in 2004, whereas the channeling of coxibs to patients with cardiovascular disease remained constant. Less than 15% of all coxib users had history of ischemic coronary or cerebrovascular disease. Among coxib users with increased risk for NSAID-related gastrointestinal disorders, 27% had history of ischemic coronary or cerebrovascular disease. CONCLUSION: This study demonstrates that coxibs were preferentially prescribed to patients with risk factors for NSAID-related gastrointestinal disorders and/or cardiovascular diseases. Only one-quarter of coxib users with increased risk for NSAID-related gastrointestinal complications had cardiovascular conditions compatible with recent European safety contraindications for coxibs.