Mind the gap: Efficacy versus effectiveness and pivotal prostate cancer clinical trial demographics

Abstract

The results of clinical trials are critical to informing the care of patients with cancer. These results are used as a basis for the regulatory approval of new interventions, to construct treatment guidelines or pathways, and to facilitate shared medical decisions. However, despite being considered among the highest levels of evidence in the evidence-based medicine paradigm, clinical trials are not without limitations. Trials are expensive to conduct, typically generate results slowly, may not be published, may not be published in a transparent manner, or may be discontinued without completing enrollment. [1][2][3] Perhaps the most often cited limitation of clinical trials, however, is the potential lack of generalizability of the results. Restrictive eligibility criteria and socioeconomic and geographic barriers to participation often result in study populations that do not resemble the general population of patients with the disease being studied, leading to a gap between the "efficacy" and "effectiveness" of new treatments.In this issue of Cancer, Wissing and colleagues explore a concerning potential source of poor generalizability of prostate cancer clinical trial results submitted to the US Food and Drug Administration (FDA) to support marketing approval-the under-representation of racial minorities. 4 Poor representation of racial minorities in cancer clinical trials has been reported by other investigators. 5,6 However, this issue is particularly important in prostate cancer, a disease with a higher incidence, a greater likelihood of advanced stage at presentation, and higher age-adjusted mortality in black men compared with white men. 7,8 The causes of these disparities are likely multifactorial, including both differences in access to care and disease biology. Because there have been more new drugs approved by the FDA for the treatment of advanced prostate cancer in the past 5 years compared with the several preceding decades, this analysis of pivotal trials is especially timely.For their analysis, Wissing and colleagues used a data set of 17 international pivotal prostate cancer clinical trials that were conducted between 1993 and 2013 and involved approximately 40,000 patients. It is noteworthy, but perhaps not surprising, that they demonstrated a decrease in the representation of patients from the United States, compared with European countries, over time. For trials initiated between 1993 and 2004, 47.7% and 9.5% of enrollment was from the United States and Eastern Europe, respectively. For trials initiated between 2005 and 2013, 29.2% and 13.5% of enrollment was from the United States and Eastern Europe, respectively. The enrollment of racial minorities was relatively consistent over time, accounting for approximately 5% to 10% of the study populations. Racial minority enrollment was highest in the United States (approximately 7%), the country with the largest nonwhite population in the data set based on census data. Of concern, enrollment of racial minorities was virtually nonexistent in Eastern E...

Assessing the efficacy‐effectiveness gap for cancer therapies: A comparison of overall survival and toxicity between clinical trial and population‐based, real‐world data for contemporary parenteral cancer therapeutics

“…Efficacy is defined as the performance of a treatment in a controlled, “ideal” setting, and is most commonly measured in randomized control trials (RCTs), which attempt to minimize potential bias affecting the internal validity of an intervention's effects on outcome through randomization and stratification . Clinical trials play a crucial role in informing care for patients with cancer as their results shape the regulatory approval of new treatments and lead to the creation of treatment guidelines . In addition, oncologists use survival and toxicity data from clinical trials to counsel patients, inform decision making, and obtain consent for treatment.…”

“…1,2 Clinical trials play a crucial role in informing care for patients with cancer as their results shape the regulatory approval of new treatments and lead to the creation of treatment guidelines. 1,3 In addition, oncologists use survival and toxicity data from clinical trials to counsel patients, inform decision making, and obtain consent for treatment. Alternatively, effectiveness refers to the treatment's performance in the "real-world" setting, the measurement of which is obtained through observational studies that have high external validity and thus, generate evidence for the generalizability of the therapy's effect.…”

Qualitative study of Oncology Clinicians’ Perceptions of Barriers to Offering Clinical Trials to Underserved Populations

“…5 A "gold standard" of clinical research, clinical trials are referenced for the approval of new treatments and are used to create treatment guidelines. 6 Findings from clinical trials are thus critical to informing the care of individuals with cancer however adequate representation of all patients is crucial to ensure the generalizability of trial findings. Despite national mandates, ethnic/racial minority and socioeconomically disadvantaged patients remain underrepresented.…”