The Role of Clinical Trial Participation in Cancer Research: Barriers, Evidence, and Strategies

Abstract

Fewer than one in 20 adult patients with cancer enroll in cancer clinical trials. Although barriers to trial participation have been the subject of frequent study, the rate of trial participation has not changed substantially over time. Barriers to trial participation are structural, clinical, and attitudinal, and they differ according to demographic and socioeconomic factors. In this article, we characterize the nature of cancer clinical trial barriers, and we consider global and local strategies for reducing barriers. We also consider the specific case of adolescents with cancer and show that the low rate of trial enrollment in this age group strongly correlates with limited improvements in cancer population outcomes compared with other age groups. Our analysis suggests that a clinical trial system that enrolls patients at a higher rate produces treatment advances at a faster rate and corresponding improvements in cancer population outcomes. Viewed in this light, the issue of clinical trial enrollment is foundational, lying at the heart of the cancer clinical trial endeavor. Fewer barriers to trial participation would enable trials to be completed more quickly and would improve the generalizability of trial results. Moreover, increased accrual to trials is important for patients, because trials provide patients the opportunity to receive the newest treatments. In an era of increasing emphasis on a treatment decision-making process that incorporates the patient perspective, the opportunity for patients to choose trial participation for their care is vital.

Figure 1

Model pathway of trial enrollment process

Figure 2. Increase in Absolute Percentage of Annual 5-Year Cancer-Specific Survival Rates since 1973–1975 by Calendar Year and Age

Baseline is 1973–1975 average. Kaposi sarcoma is excluded due to HIV/AIDS epidemic during the 1980s and early 1990s; thyroid cancer is excluded because of overdiagnosis and increasing survival inflation. Regressions are 4° polynomials. Data source is SEER 9 regions.

Figure 3. Comparison of Average Percent Change (APC) in the 5-Year Cancer Survival Rate and Treatment Trial Accruals, by 5-Year Age Intervals

The open columns represent trial accruals during 2001–2006 and the colored bars the average percent change (APC) in 5-year relative survival rate of all invasive cancer except Kaposi sarcoma during 1985–1999. The red bars indicate the AYA age group. The inset compares the APC in 5-year survival rate with the treatment trial accruals. Accrual data from the NCI Cancer Therapy Evaluation Program (CTEP) were provided by Steve Friedman, Michael Montello, Troy Budd and Samantha Finnegan via the Freedom of Information Act. Survival data were obtained from SEER 9 Regions. Kaposi sarcoma is excluded from the survival statistic since the HIV/AIDS epidemic during the 1980s and early 1990s substantively altered the overall cancer survival rate in AYAs during those years.

Figure 4. Comparison of Average Percent Reduction in the Annual National Cancer Mortality Rate and Treatment Trial Accruals, by 5-Year Age Intervals, Age <40

The open columns represent trial accruals during 2000–2006 and the colored bars the average percent reduction in national cancer mortality rate during 1990–1998. The red bars indicate the AYA age group. The inset compares the mortality rate reduction with the treatment trial accruals. Accrual data from the NCI Cancer Therapy Evaluation Program (CTEP) were provided by Steve Friedman, Michael Montello, Troy Budd and Samantha Finnegan via the Freedom of Information Act. Mortality data were obtained from the National Center for Health Statistics via the SEER program.

Figure 5. Comparison of 2001–2003 and 2007–2009 for Annual Accruals to Treatment Trials sponsored by National Cancer Institute (NCI)-Sponsored Cooperative Groups and NCI-Designated Cancer Centers (red curves) and Accrual Proportion of All Patients in the U.S. with Invasive Cancer onto the Trials by 5-Year Age Intervals (green curves), by Single Years of Age

The heavy curves represent 2007–2009 and the thin curves 2001–2003. Accrual data from the NCI Cancer Therapy Evaluation Program (CTEP) were provided by Steve Friedman, Michael Montello, Troy Budd and Samantha Finnegan via the Freedom of Information Act. Accrual proportion (%) was estimated from cancer incidence in SEER 9 regions and population data from the U.S. Census Bureau.^,

Figure 6. 5-year Leukemia-Specific Survival Rates in Patients with Acute Lymphoblastic Leukemia (ALL) Diagnosed during 2000–2012, and Estimated ALL Treatment Trial Accrual Proportion during 2000–2009, by Single Years of Age

Each year of age was averaged from 2 consecutive years. Joinpoint analysis of survival data identified ages 17 and 20; linear regressions for survival data are for age ranges 5–17, 17–20, and 20–70 years. Survival data were obtained from SEER 18 regions. Accrual data from the NCI Cancer Therapy Evaluation Program (CTEP) were provided by Steve Friedman, Michael Montello, Troy Budd and Samantha Finnegan via the Freedom of Information Act. Accrual proportion (%) was estimated from cancer incidence in SEER 9 regions and population data from the U.S. Census Bureau.^,

Figure 7. Estimated Treatment Trial Accrual Proportion of Patients Diagnosed with Cancer during 2008–2010 by Single Year of Age and the History of SEER Representation of the United States Population

Modified from Bleyer A. Accrual data from the NCI Cancer Therapy Evaluation Program (CTEP) were provided by Steve Friedman, Michael Montello, Troy Budd and Samantha Finnegan via the Freedom of Information Act. Accrual proportion (%) was estimated from cancer incidence in SEER 9, SEER13, and SEER18 regions and population data from the U.S. Census Bureau.^,,,