Using clinical trial data and linked administrative health data to reduce the risk of adverse events associated with the uptake of newly released drugs by older Australians: a model process.

BACKGROUND: The study was undertaken to evaluate the contribution of a process which uses clinical trial data plus linked de-identified administrative health data to forecast potential risk of adverse events associated with the use of newly released drugs by older Australian patients. METHODS: The study uses publicly available data from the clinical trials of a newly released drug to ascertain which patient age groups, gender, comorbidities and co-medications were excluded in the trials. It then uses linked de-identified hospital morbidity and medications dispensing data to investigate the comorbidities and co-medications of patients who suffer from the target morbidity of the new drug and who are the likely target population for the drug. The clinical trial information and the linked morbidity and medication data are compared to assess which patient groups could potentially be at risk of an adverse event associated with use of the new drug. RESULTS: Applying the model in a retrospective real-world scenario identified that the majority of the sample group of Australian patients aged 65 years and over with the target morbidity of the newly released COX-2-selective NSAID rofecoxib also suffered from a major morbidity excluded in the trials of that drug, indicating a substantial potential risk of adverse events amongst those patients. This risk was borne out in post-release morbidity and mortality associated with use of that drug. CONCLUSIONS: Clinical trial data and linked administrative health data can together support a prospective assessment of patient groups who could be at risk of an adverse event if they are prescribed a newly released drug in the context of their age, gender, comorbidities and/or co-medications. Communication of this independent risk information to prescribers has the potential to reduce adverse events in the period after the release of the new drug, which is when the risk is greatest.Note: The terms 'adverse drug reaction' and 'adverse drug event' have come to be used interchangeably in the current literature. For consistency, the authors have chosen to use the wider term 'adverse drug event' (ADE).

Improving benefit-harm assessment of glucocorticoid therapy incorporating the patient perspective: The OMERACT glucocorticoid core domain set.

OBJECTIVE: Our primary objective was to develop an Outcome Measures in Rheumatology (OMERACT) core domain set to capture the impact of glucocorticoids (GC), both positive and negative, on patients with Rheumatic conditions. METHODS: The OMERACT Filter 2.1 was used to guide core domain selection. Systematic literature reviews, qualitative studies and quantitative surveys were conducted by the OMERACT GC Impact working group to identify candidate domains for a core domain set. A summary of prior work and Delphi exercise were presented at the OMERACT 2020 virtual GC workshop. A proposed GC Impact core domain set derived from this work was presented for discussion in facilitated breakout groups. Participants voted on the proposed GC Impact core domain set. RESULTS: 113 people, including 23 patient research partners, participated in two virtual workshops conducted at different times on the same day. The proposed mandatory domains to be evaluated in clinical trials involving GCs were: infection, bone fragility, hypertension, diabetes, weight, fatigue, mood disturbance and death. In addition, collection of disease specific outcomes was included in the core domain set as "mandatory in specific circumstances". The proposed core domain set was endorsed by 100% (23/23) of the patient research partners and 92% (83/90) of the remaining participants, including clinicians, researchers and industry stakeholders. CONCLUSION: A GC Impact core domain set was endorsed at the OMERACT 2020 virtual workshop. The OMERACT GC Impact working group will now progress to identify, develop and validate measurement tools to best address these domains in clinical trials.

Manufacturing the truth: From designing clinical trials to publishing trial data.

This paper expands on some of the points made by Deepak Natarajan on techniques used in designing clinical trials of new drugs to ensure favourable outcomes. It also considers the nexus between the manufacturers of new drugs and the publishers of medical journals in which edited versions of these favourable outcomes are presented to the medical fraternity. The argument will be illustrated by referring to the clinical trials of rofecoxib (Vioxx®) and etoricoxib (Arcoxia®). Both these drugs are COX-2 selective non-steroidal anti-inflammatory drugs (NSAIDs) manufactured by Merck and Co. Because of the unparalleled access to Merck's internal confidential documents, due to the subpoenaing of these documents by government and private individuals in civil and criminal actions, we are still learning about the company's unconscionable acts. What we learn can inform our judgement concerning published reports of both new and old drugs.

Seeking evidence from medical research consumers as part of the medical research process could improve the uptake of research evidence.

Concerns have been expressed about gaps between available medical research evidence and current medical practice. These gaps have been attributed to process problems with the implementation of evidence previously judged to be appropriate, rather than to problems with the appropriateness of the evidence provided for implementation. Two such 'appropriateness' problems are the applicability of research evidence to an individual patient, and the acceptability to an individual patient of a proposed treatment. Part of both these problems is due to the pre-eminence of the scientific paradigm within the medical research domain, and of the randomized controlled clinical trial within that domain. However, there is an opportunity beneficially to address both these problems by supporting reciprocal communication between medical research 'producers' and medical research 'consumers'--both practising clinicians and patients' representatives--in the setting of research priorities, selection of topics for research, development of research questions and study designs, in-progress reviewing, and final reporting of medical research projects. Such communication could allow researchers to understand, and respond to, clinicians' and patients' inputs concerning the applicability, utility and acceptability issues that will ultimately affect whether, and how, medical research findings can be applied. Such communication could also assist with some post-research implementation issues: integration of appropriate evidence into everyday practice; access to appropriate information sources; and a critical lack of necessary time.