Individualized versus standardized risk assessment in patients at high risk for adverse drug reactions (IDrug) - study protocol for a pragmatic randomized controlled trial

Abstract

Background: Elderly patients are particularly vulnerable to adverse drug reactions, especially if they are affected by additional risk factors such as multimorbidity, polypharmacy, impaired renal function and intake of drugs with high risk potential. Apart from these clinical parameters, drug safety and efficacy can be influenced by pharmacogenetic factors. Evidence-based recommendations concerning drug-gene-combinations have been issued by international consortia and in drug labels. However, clinical benefit of providing information on individual patient factors in a comprehensive risk assessment aiming to reduce the occurrence and severity of adverse drug reactions is not evident. Purpose of this randomized controlled trial is to compare the effect of a concise individual risk information leaflet with standard information on risk factors for side effects.

Methods/design: The trial was designed as a prospective, two-arm, randomized, controlled, multicenter, pragmatic study. 960 elderly, multimorbid outpatients in general medicine are included if they take at least one high risk and one other long-term drug (polymedication). As high risk "index drugs" oral anticoagulants and antiplatelets were chosen because of their specific, objectively assessable side effects. Following randomization, test group patients receive an individualized risk assessment leaflet evaluating their personal data concerning bleeding- and thromboembolic-risk-scores, potential drug-drug-interactions, age, renal function and pharmacogenetic factors. Control group patients obtain a standardized leaflet only containing general information on these criteria. Follow-up period is 9 months for each patient. Primary endpoint is the occurrence of a thromboembolic/bleeding event or death. Secondary endpoints are other adverse drug reactions, hospital admissions, specialist referrals and medication changes due to adverse drug reactions, the patients' adherence to medication regimen as well as health related quality of life, mortality and resulting costs.

Discussion: Despite extensive evidence of risk factors for adverse drug reactions, there are few prospective trial data about an individualized risk assessment including pharmacogenetic information to increase patient safety. By conducting a health economic analysis, we will evaluate if the application of an individualized drug therapy in daily routine is cost-effective.

Trial registration: German Clinical Trials Register: DRKS00006256 , date of registration 09/01/15.

Keywords: ADR risk assessment; Adverse drug reaction; Clinical decision support system; Drug interaction; Elderly; Individualized medicine; Pharmacogenetics; Polymedication.

Fig. 1

Workflow IDrug study. Each GP provides a list of all patients meeting the inclusion criteria. The order of patient enrollment is random. Following randomization to a study arm, the patients receive either a standardized or an individualized risk assessment leaflet and are followed up for 9 months. 870 patients will be required, and considering an estimated dropout rate of 10 % 960 patients need to be included. At the end of the study, both groups will be compared regarding primary and secondary endpoints

Fig. 2

Scheme of the risk assessments. Both versions of risk assessment leaflets contain general information on the following risk factors for ADR: HAS-BLED- and CHA2DS2-VASc-Score, drug-drug-interactions, age, renal function and pharmacogenetic factors. The individualized risk assessments additionally include a personalized evaluation of the patient’s personal data