Clinical Trial of a New Software ENgine for the Assessment & Optimization of Drug and Non-drug Therapy in Older peRsons

Phase I is designed to test the electronic case report form (eCRF) and the ADR ascertainment method in the six clinical sites in advance of Phase II (randomization phase). In Phase I, we recruited 644 older multi-morbid patients from the 6 clinical sites. After obtaining written informed consent, patients' demographic, clinical and medication details were entered to the eCRF. In the event of one a 12 item Trigger List of adverse clinical events occurring, the eCRF automatically generated a Trigger List assessment proforma. The 12 items in the Trigger List included: 1. New onset falls 2. New onset unsteady gait 3. Acute kidney injury 4. Symptomatic orthostatic hypotension 5. Serum electrolyte disturbance 6. Symptomatic bradycardia 7. New onset major constipation 8. Acute bleeding 9. Acute dyspepsia/nausea/vomiting 10. Acute diarrhea 11. Delirium 12. Symptomatic hypoglycemia In addition, we have included 'Unspecified adverse event' in order to capture the wide range of well recognized ADRs associated with various medications. For example, the rapid onset of a generalized maculopapular rash in a patient with penicillin hypersensitivity would be identified as an ADR under the 'Unspecified adverse event' category. ADR adjudication in Phase I was blinded and no ADR adjudications were undertaken by the site principal investigator (PI). ADRs were defined as 'definite', probable', 'possible', 'unlikely' or 'indeterminate' according to WHO-UMC ADR causality critria. ADR severity was defined according to a modified Hartwig ADR severity scale ranging from Level 1 (trivial) to Level 7 (fatal). Consensus on ADR causality was achieved through a potential endpoint adjudication committee (PEPAC), whose members were the 6 clinical site PI's. A matrix for achieving consensus was devised, such that there was a final decision on the causality of all potential ADRs.