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


CONCLUSIONS
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.


BACKGROUND
German Clinical Trials Register: DRKS00006256 , date of registration 09/01/15.
Research Division, Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany.|Centre for Translational Medicine, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Julia Carolin
JC
Stingl
Research Division, Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany. katharina.kaumanns@bfarm-research.de.|Centre for Translational Medicine, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany. katharina.kaumanns@bfarm-research.de.
Katharina Luise
KL
Kaumanns
Research Division, Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany.|Centre for Translational Medicine, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Katrin
K
Claus
Research Division, Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany.|Centre for Translational Medicine, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Marie-Louise
ML
Lehmann
Institute of General Practice and Family Medicine, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Kathrin
K
Kastenmüller
Institute of General Practice and Family Medicine, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Markus
M
Bleckwenn
Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Gunther
G
Hartmann
Research Division, Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany.|Centre for Translational Medicine, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Michael
M
Steffens
Research Division, Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany.
Dorothee
D
Wirtz
Research Division, Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany.
Ann-Kristin
AK
Leuchs
Research Division, Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany.
Norbert
N
Benda
Department of Economics and Management, Wilhelm Löhe University of Applied Sciences, Merkurstraße 41, 90763, Fürth, Germany.
Florian
F
Meier
Department of Health Management, University of Erlangen-Nürnberg, Lange Gasse 20, 90403, Nürnberg, Germany.
Oliver
O
Schöffski
Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Stefan
S
Holdenrieder
Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Christoph
C
Coch
Institute of General Practice and Family Medicine, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Klaus
K
Weckbecker
D000368:Aged; D000369:Aged, 80 and over; D000066491:Clinical Decision-Making / Q000379:methods*; D002985:Clinical Protocols; D020000:Decision Support Systems, Clinical; D003661:Decision Support Techniques; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis* / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D019338:Polypharmacy; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D016037:Single-Blind Method
ADR risk assessment; Adverse drug reaction; Clinical decision support system; Drug interaction; Elderly; Individualized medicine; Pharmacogenetics; Polymedication