This research project is in progress. PCORI will post its findings here within 90 days after our final review is complete. In the meantime, results have been published in peer-reviewed journals, as listed below.
Although "evidence-based medicine" has become the dominant paradigm for shaping clinical recommendations and guidelines, recent work has emphasized that there is a fundamental incongruence between the evidence available from clinical trials (i.e., the overall or average effect of a treatment in the study population) versus the information that is needed for most medical decisions (i.e., what treatment is best for an individual patient).
While the field of clinical theraputics has long understood that treatments may work differently in different patients (a concept known as heterogeneity of treatment effect), developing reliable methods for the estimation of individual patient effects has proven difficult. Investigators have traditionally tried to discover heterogeneity by re-examining treatment effects for subgroups defined by single variables, but these analyses are generally inadequate and not truly representative of the complex combination of factors that represent individual patients.
Multivariable risk stratification may more effective identify patients in whom a therapy offers a greater potential net benefit (that is, benefit minus harm). This project re-analyzes two randomized clinical trials with the intent to identify patients at potentially higher risk of experiencing either benefits or adverse effects from the interventions studied (i.e., a positive or negative net benefit), in order to better personalize individual decision making.
The first trial involves patients with insulin resistance and a prior stroke or TIA deciding whether to take pioglitazone for the prevention of stroke or myocardial infarction, given its adverse event profile of weight gain, peripheral edema, and bone fractures. The second trial examines the potential for cardiotoxicity among women with breast cancer receiving anthracycline chemotherapy.
*All proposed projects, including requested budgets and project periods, are approved subject to a programmatic and budget review by PCORI staff and the negotiation of a formal award contract.