WP01 - Design & Validation of new Adverse Drug Reaction Risk in Older Persons (ADRROP) scale

Objectives

  • determine the significant risk factors for ADRs in hospitalized older people from a substantial database of older hospitalized people in whom ADRs have been clearly defined
  • design of the new ADRROP (ADR Risk in Older People) scale based on ADR risk factors
  • prospectively validate the ADRROP scale in an independent population consisting of 540 patients to be recruited from each of the 6 participating centres in months 6-16 of Phase I of the SENATOR Trial
  • develop a stand-alone software interface to calculate the new validated ADRROP

Workpackage Description

Using the existing database of verified ADRs in older people who have been hospitalized with acute illness at Cork University Hospital, the plan is to identify those risk factors that are clearly associated with verified ADRs, using a statistical methodology similar to that used in the recently published GerontoNet ADR Risk Scale (Onder et al.). Variables associated with ADR at p < 0.2 on univariate analysis will be entered into a hierarchical multivariate model in a stepwise fashion. Only one of any highly correlated group of variables will be selected for entry into the ADRROP model. Explanatory variables will be standardized using the standard deviation of their distribution (for continuous variable), and quartiles for ordinal variables. The categorical data will be expressed in a binary fashion. Retained variables with be weighted in accordance with their effect size. Appropriate model diagnostics and scale calibration assessments will be undertaken. This work will be undertaken by the Trial Co-ordinating Centre at UCC, Cork (Ireland) in conjunction with Prof. Petrovic, one of the authors of the GerontoNet ADR Risk Scale, and statistical experts in the Health Research Board Clinical Research Facility at UCC.

Task 1: Evaluation of ADR Risk Factors from the pre-existing UCC older person ADR database.

Firstly the scientists will analyze data on ADRs in the UCC Older Person ADR database totalling 1674 hospitalized older people in whom ADRs were identified and verified by WHO-UMC criteria for ‘probable’ or ‘definite’ ADRs. The UCC database shows a hospital ADR rate on admission of 24%. The observed nosocomial (hospital-acquired) ADR incidence rate from a currently running RCT is 21.2% during the index hospital admission among those older people with acute illness admitted under the care of specialist departments other than Geriatric Medicine. It will be designed and built up the ADRROP scale from the odds ratio analysis of the verified ADRs database in the 1674 older patient ADR database, in which statistically significant ADR risk factors are identified and numerically rated according to comparative importance.

Task 2: Prospective validation of the ADRROP Risk Scale in 6 European centres.

Task 2 will focus to validate ADRROP using the SENATOR Trial database for the initial 540 patients with acute illness, recruited from each of the 6 participating centres (UCC, UGENT, SERMAS, NHSG, INRCA, LUH) in months 6-16 of Phase I (Control arm; as per WP08). This represents a larger validation sample than that used in the GerontoNet prospective validation study.

Task 3: Finalization of the ADRROP Risk Scale for use in the SENATOR software engine.

As described in the GerontoNet ADR risk scale, the incidence of ADRs in each of the 5 ADRROP scale quintiles will be calculated to ensure validity of ADRROP. Receiver-operator-curve analysis will be undertaken to ensure the ADR predictive value of ADRROP. Ultimately the ADRROP calculation will be incorporated into the SENATOR software; initially was developed as a stand-alone instrument and manually entered the ADRROP score into the SENATOR interface, in order to avoid delaying the SENATOR development programme and language translation in time for the trial.

Task 4: End of Trial Refinement of ADRROP score.

Model estimates will be further refined using the entire control arm population of SENATOR (n=900) and using the adjudication committee’s approved ADRs, as well oral anticoagulation related ADRs, following the conclusion of the trial.

WP Leader

Dr. Denis O´Mahony (UCC)

Participating Partners

University College Cork (UCC)
Ghent University Hospital (UGENT)