The emerging relevance of heterogeneity of treatment effect in clinical care: A study using stage IV prostate cancer as a model
Aim: Heterogeneity of treatment effect (HTE) occurs when patient factors modify a treatment’s effect on health outcomes due to interactions between these factors and the treatment. This article reviews evidence regarding HTE in stage IV prostate cancer (S4PC). Method: A systematic literature review was conducted in the MEDLINE and PubMed databases. Inclusion criteria required that articles examine the treatment-related impact of HTE factors on survival, adverse events or health-related quality of life in S4PC patients. The quality of evidence was graded good, fair or poor based on Agency for Healthcare Research and Quality guidelines. Results: The search identified 2659 articles, of which 92 met the inclusion/exclusion criteria. HTE in S4PC was studied for biologic factors including age, race, clinical signs/symptoms, measures of S4PC disease severity, genetic factors, laboratory data, prior treatment, concurrent medications and comorbidities. Nonbiologic factors that were studied included social, geographic and dietary factors. Age and race seldom showed any correlation with S4PC outcomes. Conclusion: Diverse biologic and nonbiologic factors contribute to HTE in S4PC. This review in S4PC also provides an approach for examining HTE for other medical conditions. Ultimately, such knowledge can help oncologists prescribe more personalized medicine, help patients make more informed treatment choices, and inform policy-making and treatment coverage decisions.