Interviewer variability - quality aspects in a case-control study.

Quality assurance and quality control are important for the reliability of case-control studies. Here we describe the procedures used in a previously published study, with emphasis on interviewer variability. To evaluate risk factors for acute pancreatitis, information including previous diagnoses and medication was collected from medical records and by telephone interviews from 462 cases and 1781 controls. Quality assurance procedures included education and training of interviewers and data validity checks. Quality control included a classification test, annual test interviews, expert case validation, and database validation. We found pronounced variations between interviewers. The maximal number of interviews per day varied from 3 to 9. The adjusted average (95% CI) number of diagnoses captured per interview of cases was 4.1 (3.8-4.3) and of controls 3.5 (3.4-3.7) (excluding one deviating interviewer). For drugs, the average (95% CI) number per interview was 3.9 (3.7-4.1) for cases and 3.3 (3.2-3.4) for controls (excluding one deviating interviewer). One of the fourteen interviewers deviated significantly from the others, and more so for controls than for cases. This interviewer's data ;were excluded. Nonetheless, data concerning controls more frequently needed correction and supplementation than for cases. Erroneous coding of diagnoses and medication was also more frequent among controls. Thus, a system for quality control of coding practices is crucial. Variability in interviewers' ability to ascertain information is a possible source of bias in interview-based case-control studies when "blinding" cannot be achieved.

Acid-suppressing drugs and gastroesophageal reflux disease as risk factors for acute pancreatitis--results from a Swedish Case-Control Study.

PURPOSE: To study risk factors for acute pancreatitis, here with emphasis on gastro-intestinal diseases and their treatments. METHODS: Population based case-control study covering four areas in Sweden encompassing 2.2 million inhabitants. Included were 462 incident cases of acute pancreatitis aged 20-85 years, hospitalized from 1 January 1995-31 May 1998, and 1,781 unmatched controls randomly selected from the study base using a population register. Information was captured from medical records and structured telephone interviews. RESULTS: Current use of H(2) antagonists starting within 6 months of index-date was associated with acute pancreatitis with an adjusted OR of 4.9 (95% confidence interval (CI) 1.6-15), and current use of proton pump inhibitors (PPIs) with an adjusted OR of 3.2 (95%CI 1.4-7.4). For both drug classes, the ORs tended to be higher at higher doses. Gastritis/gastro-esophageal reflux disease (GERD) within the last 12 months not treated with PPIs or H(2)-antagonists and inflammatory bowel disease (IBD) not treated with anti-inflammatory or immunosuppressive drugs were associated with development of acute pancreatitis with adjusted odds ratios (OR) of 1.9 (95%CI 1.2-3.0) and 5.1 (95%CI 2.0-13) respectively. CONCLUSIONS: Current IBD without treatment and gastritis/GERD without treatment were found to be associated with increased risks to develop acute pancreatitis but the nature of the latter association needs to be further evaluated. On balance, we judge that the observed associations between current use of H(2)-antagonists and PPIs and increased risk of acute pancreatitis are unlikely to be explained by bias.

Monitoring outcomes of pregnancy following drug exposure: a company-based pregnancy registry program.

Women who discover they are pregnant after exposure to a drug and pregnant women who have a condition that requires continued treatment during pregnancy are told to balance the benefits and risks of the exposure to justify continuation of treatment, discontinuation of treatment or, possibly, pregnancy termination. However, there are limited data available to inform decision-making. The Merck Pregnancy Registry Program is a company-run pregnancy registry whose objective is to acquire and analyse information on drug exposures and pregnancy outcomes to better describe the safety profile of Merck products used during pregnancy. Information is collected from women and healthcare providers who call to report drug exposure during pregnancy. Prospective pregnancies are followed up to outcome and data are collected via questionnaires, telephone calls and a review of medical records. Reports are classified as prospective (information received prior to knowledge of pregnancy outcome) or retrospective (received after the outcome is known). Congenital anomaly reports are assessed for timing of exposure, maternal age and medical history, biological plausibility and concomitant medication exposures. Rates of pregnancy outcomes and birth defects in the prospective cohort are computed and confidence intervals are calculated to reflect the strength of the finding based on the sample size. Rates of pregnancy outcomes in the Pregnancy Registry are compared with the rates of pregnancy outcomes in the general US population and, if available, in subpopulations with the relevant disease states. The limitations of post-marketing surveillance are well known as voluntary reporting of individuals and healthcare professionals is known to be subject to various types of bias. Small sample size is another major limitation. However, the strength of the registry lies in its ability to gather pregnancy outcome reports early in the life of a product and to recognise and analyse unusual birth defects. Our data suggest that pregnancy registries can be used to review human exposure data in a systematic fashion so that useful information can be shared with women and their healthcare providers. The use of the pregnancy registry design has allowed for the collection and analysis of data on the effects of drug exposures on human pregnancies that have otherwise been difficult to obtain.

Dose-response relationships between individual nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) and serious upper gastrointestinal bleeding: a meta-analysis based on individual patient data.

AIMS: To define by amalgamation of data obtained in contemporaneous case-control studies, the risks associated with individual nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) according to doses used. METHODS: Meta-analysis of individual patient data from three retrospective case-control studies using similar data collection protocols was carried out in hospitals in Catalonia, England, Scotland and Sweden. 2472 cases of upper gastrointestinal bleeding and 5877 controls were studied. Main outcome measures were risks associated with individual NANSAIDs according to dose used and the period of time for which they were given. RESULTS: Ibuprofen showed the lowest odds ratio (OR = 1.7; 95% confidence interval 1.1, 2.5), followed by diclofenac (4.9; 3.3, 7.1), indomethacin (6.0; 3.6, 10.0), naproxen (9.1; 6.0-13.7), piroxicam (13.1; 7.9-21.8) and ketoprofen (34.9; 12.7, 96.5). Striking dose-response relationships were seen with four to eight-fold increases in risk within conventionally used dose ranges for all except ketoprofen, where numbers were too few to allow dose analysis. Across the class, risk was highest during the first week of use (11.7; 6.5, 21.0), decreased thereafter with continuing use (5.6; 4.6, 7.0), and fell to 3.2 (2.1, 5.1) 1 week after discontinuing use. Concurrent use of more than one NANSAID substantially increased risk. CONCLUSIONS: The risk of upper gastrointestinal bleeding with NANSAIDs varies twenty-fold depending on the drug, and by three to seven-fold depending on the dose chosen. Risk is maximal during the first week and decreases thereafter. Paracetamol (acetaminophen) is not associated with upper gastrointestinal bleeding at any dose and should be the first-line analgesic wherever possible.

A Swedish case-control network for studies of drug-induced morbidity--acute pancreatitis.

OBJECTIVE: To evaluate risk factors - notably drugs - for developing acute pancreatitis. METHODS: A population-based, case-control study, encompassing 1.4 million inhabitants aged 20-85 years from four regions in Sweden between 1 January 1995 and 31 May 1998. A total of 462 cases were hospitalised in surgical departments with their first episode of acute pancreatitis without previously known biliary stone disease. From a population register, 1781 controls were randomly selected. Information was obtained from medical records and through telephone interviews. RESULTS: Fifty-seven percent of the cases were males. An expert group found evidence for biliary stones in 50% of the cases, alcohol intake in 23%, but in 29% neither of these factors were present. In all, "other" factors, e.g. drugs, could have contributed to the development of acute pancreatitis in 52% of the cases. In a multivariate analysis, the adjusted odds ratios (ORs) for H(2) antagonists were 2.4 (95% CI 1.2-4.8) for proton pump inhibitors (PPIs), 2.1 (1.2-3.4) for non-steroidal anti-inflammatory drugs (NSAIDs), 2.3 (1.3-4.0) for those derived from acetic acid and 1.9 (1.1-3.2) for antibacterials for systemic use. Significant ORs were found for a history of gastrointestinal tract disorders [1.5 (1.1-1.9)] and inflammatory bowel disease (IBD) [3.4 (1.5-7.9)]. Smoking was significantly associated with acute pancreatitis [1.7 (1.2-2.1)] and, for those smoking more than 20 cigarettes per day, the OR was 4.0 (2.2-7.5). Alcohol in moderate amounts did not increase the risk, but for those drinking more than 420 g alcohol per week the OR was 4.1 (2.2-7.5). CONCLUSION: In addition to cholelithiasis, smoking and heavy alcohol use, drugs may be an important risk factor for acute pancreatitis.

Adverse drug reactions as a cause for admissions to a department of internal medicine.

PURPOSE: To assess the occurrence and pattern of adverse drug reactions as a cause for acute hospital admission. METHODS: In 681 randomly selected patients, acutely admitted to a clinic of internal medicine at a Swedish university hospital, information was collected from their medical records about current symptoms and use of drugs, previous diseases and the results of medical investigations and tests. In addition, a standardized interview according to a questionnaire was carried out. A group of experts in clinical pharmacology assessed the data obtained from the patients' case records and the results of the interviews, and then, according to WHO criteria, judged the probability that an adverse drug reaction could have caused or contributed to the actual admission to hospital. RESULTS: Out of the 681 cases included, 94 (13.8%) had symptoms and signs that were judged as drug-related and that had caused or contributed to the admission. Eighty-two patients (12.0%) had altogether 99 symptoms that were classified as adverse drug reactions. Of these, 91% were type A reactions. The relationship between the medication and the reaction was judged certain in eight, probable in 17, and possible in 74 cases. The most common adverse drug reactions were cardiovascular (36.3%). Twelve patients (1.8%) had symptoms indicating intoxications. CONCLUSIONS: The prevalence of drug-related problems causing or contributing to admission to a clinic of internal medicine is high and is dominated by type A reactions, i.e. reactions in principle predictable and preventable. This implies a possibility to increase drug safety by preventive measures.