Information deficits in the summary of product characteristics preclude an optimal management of drug interactions: a comparison with evidence from the literature.

OBJECTIVE: To compare comprehensiveness and accuracy of drug interaction information in the German summary of product characteristics (SPC) with current evidence from the literature and to evaluate the SPC's usefulness with respect to management of drug interactions. METHODS: Information on clinically relevant drug interactions was compared between the SPC and three standard information sources on drug interactions (DRUGDEX, Hansten/Horn's Drug Interactions Analysis and Management, Stockley's Drug Interactions) according to five consecutive criteria (inclusion, appropriateness of class labelling, effect description, management recommendation, explicit dose adjustment). Using medication data of an outpatient population (n=4,949), we determined what percentage of insufficiently characterized combinations indeed occurred in outpatients treated with combination drug therapy. RESULTS: Only for 33% (192/579) of the evaluated combinations did SPCs provide drug interaction information equivalent to the evidence from the published literature. Of the clinically relevant drug interactions, 16% were completely missing and 51% were insufficiently characterized compared with standard sources. Explicit management recommendations were either missing or differed from standard sources in 18% of the evaluated pairs of compounds. Of these missing or insufficiently characterized combinations, 12% (47/387) were indeed prescribed to outpatients. Those drug combinations for which the interaction potential was not mentioned in the SPC were received by 0.6% (32/4,949) of patients, and 4% (192/4,949) of patients received combinations that had insufficiently characterized drug interactions. CONCLUSIONS: If physicians only rely on SPC information for drug interactions, adverse events due to lacking management recommendations may occur. To meet the SPCs claim of being the basis of information for health professionals on how to use medicinal products safely and effectively, information on drug interactions should be thoroughly up-dated and expanded.

Mail surveys: obsolescent model or valuable instrument in general practice research?

QUESTION UNDER STUDY: Due to low response rates mail surveys have been called into question as research instruments in general practice. The most effective actions to reduce non-response, such as financial incentives and complex follow-up procedures, are costly. We investigated whether a good response rate is achievable with a less costly survey design, and examined the effect of increased response rates due to repeated follow-ups on survey results. METHODS: In a mail survey on drug interactions among 2000 general practitioners in south-west Germany, most well-known criteria influencing response rates were met except financial incentives. A four stage design with two reminders was applied and the time course of response was recorded. Results after both reminders were calculated with 95% confidence intervals and compared with initial results using the Jonckheere-Terpstra test with correction for multiple testing. A p <0.01 was considered significant. RESULTS: Although we did not provide financial incentives we achieved a response rate of 60.8% with our survey design. The first reminder with a simple postcard was almost three times less effective than the second reminder including another copy of the questionnaire. For only two survey questions, the answers of late respondents differed significantly from those of initial respondents (p <0.01). For these two questions, cumulative results after both reminders never differed from initial results by more than 3.7%. CONCLUSION: Even if financial incentives are not affordable, good response rates can be obtained among general practitioners when surveys are meticulously planned and implemented. Potential non-response bias introduced by those general practitioners who do not answer despite numerous reminders, cannot be tested by comparing early and late respondents. Therefore, we suggest that the impact of reminders on survey results should be assessed early. If no bias can be detected one further reminder with a copy of the questionnaire might result in estimates very similar to those after numerous reminders.

Dose individualisation in patients with renal insufficiency: does drug labelling support optimal management?

OBJECTIVE: An important information source for pharmacotherapy in populations at risk is drug labelling. We compared the recommendations for patients with renal insufficiency included in German drug labellings with evidence from the literature. METHODS: From the 120 drugs with the highest turnover in a large university hospital, all drugs with pharmacokinetics independent of renal function (n=48) and those with substantial accumulation in renal failure (n=28) were identified. For both groups of compounds, pharmacokinetic and pharmacodynamic aspects relevant for dose individualisation in those with renal insufficiency were extracted from the literature and compared with the information given in the German drug labelling. RESULTS: Over half of the labellings (15 of 26) of non-accumulating drugs without renal adverse drug reactions contained no dose recommendation for patients with renal insufficiency. The labelling of nephrotoxic compounds that do not accumulate included more frequently a recommendation to adapt the dose or to monitor than the labelling of drugs without nephrotoxic potential (15 of 22 versus 5 of 26, P=0.002). For over half of accumulating drugs (16 of 28), the dose given in the labelling depends primarily on creatinine clearance. The ratio between the labelling dose and the dose based on the pharmacokinetic concept to achieve identical plasma concentrations (Q0 concept) differed widely (0.4-2). CONCLUSIONS: When renal failure had no impact on dosing, information was often missing. Such information is however important to differentiate, whether no dose adaptation is necessary or no information is available. If dose adjustment is required, application of a uniform concept is desirable.

Requirements for a successful implementation of drug interaction information systems in general practice: results of a questionnaire survey in Germany.

OBJECTIVE: To determine drug interaction information requirements in general practice with respect to both content and mode of presentation. METHODS: In a mail survey among 2,000 general practitioners in south-west Germany, we collected information on risk evaluation of drug interactions and combinations of concern, usage of and satisfaction with the current information sources, desirable content and mode of future presentation and demographic variables. Categorical variables were compared using chi2 test. Trends were analysed with Cochran-Armitage test and determinants of literature usage with logistic regression. RESULTS: Response rate was 60.8%. The majority of general practitioners considered drug interactions a risk factor in prescribing (88.6%). For 18.2% of the drug combinations most frequently indicated as interacting, there was no published evidence of a clinically relevant interaction. More than half of the participants were dissatisfied with the information on severity, mechanism, and dose adjustment currently available in their sources. In particular, non-interacting alternatives were thought to be lacking (86.9%). Users of drug interaction software more frequently retrieved drug interaction information than non-users [odds ratio (OR) 1.95; 95% confidence intervals (CI) 1.50, 2.52], but only 28.6% of general practitioners had access to such systems. There was a significant trend towards electronic sources among younger physicians, but at present, 41.7% of general practitioners favour printed sources, and 8.8% would refuse to use electronic sources. CONCLUSION: General practitioners wish for more informative support on drug interactions, especially concerning management. Despite a trend towards electronic information sources, printed documents are presently still required to reach all prescribers.

Drug interactions in primary care: impact of a new algorithm on risk determination.

BACKGROUND: If managed adequately, many drug interactions do not result in clinical manifestations. Earlier studies may have overestimated the risk arising from drug interactions because they usually reported interaction frequencies and the severity of potential outcomes irrespective of their manageability. OBJECTIVE: Our objective was to estimate the risk associated with drug interactions in a large population when not only the severity of possible clinical events but also measures of their prevention (manageability, modulating factors) are considered. METHODS: We evaluated all drug pairs concurrently prescribed to 9481 adults aged 50 to 75 years who participated in a health-screening examination. Drug interactions were evaluated by use of an algorithm with 4 decision layers (severity, manageability, risk/benefit assessment, and patient-related risk factors), and this risk evaluation was compared with the conventional evaluation solely on the basis of severity. RESULTS: More than 52% of the patients received combination therapy. Interaction information was available in a standard source (DRUGDEX; Thomson MICROMEDEX, Greenwood Village, Colo) for only 1029 of all 13,672 individual prescribed drug pairs. Of the drug pairs, 881 (6.4%) were identified as interacting. Of these 881 interactions, 132 (15.0%) were of major severity but 101 of 132 (76.5%) were considered manageable. Only 31 (23.5%) of 132 major interactions (ie, 31/881 [3.5% of all interacting pairs]) offered no management options and should thus be avoided. CONCLUSION: For many commonly prescribed drug pairs, explicit drug interaction information is currently not available in DRUGDEX. For major interactions with published evidence, the overwhelming majority were manageable, and therefore risk estimates only based on the severity of potential outcomes will grossly overestimate the risk associated with such combinations.