AccrualNet. NIH Office of Inspector General. 6, clinical trial accruals as a proportion of ALL cases in the United States during 2000 to 2009 drops precipitously for patients age 15 to 20. We have shown data indicating a compelling relationship between the incidence of clinical trial enrollments and improvements in cancer population survival outcomes. Compared with a 1.8% enrollment fraction among white patients, lower enrollment fractions were noted in Hispanic (1.3%; odds ratio [OR] vs whites, 0.72; 95% confidence interval [CI], 0.68-0.77; P<.001) and black (1.3%; OR, 0.71; 95% CI, 0.68-0.74; P<.001) patients. Enrollment fraction, defined as the number of trial enrollees divided by the estimated US cancer cases in each race and age subgroup. Utilizing data from a prospective barriers study, this observation was confirmed.13,66 Thus, the evidence to date of income disparities in trial enrollment is fairly consistent.61 Given that trial treatment costs are not substantially different than nontrial treatment costs,67 this suggests that marginal direct costs play a role. Moreover, predetermined IRB-approved responses to anticipated user-generated content should be available to allow “immediate” responses when required, and links to the study website should be included to allow for integration of study platforms. In their role of guiding patient care, physicians may have a strong inclination toward a specific treatment for a given patient.31-33 The prospective study by Javid and colleagues found that the nature of the study regimen was cited as a reason for not discussing a trial with eligible patients by 56% of physicians.13 Physicians are also frequently concerned that clinical trial participation can interfere with the physician-patient relationship.31,34,35 Random assignment into a phase III trial in particular subjects the treatment choice to uncertainty, and physicians may anticipate that the introduction of uncertainty will subvert patient confidence in the physician’s expertise, even if, as indicated by the existence of a randomized clinical trial, multiple treatments of potentially similar efficacy are available. In this multifactorial decision-making environment, patients may face several barriers to trial participation. This is a concern because people of different ages, races, and ethnicities, may react differently to medical products. American Cancer Society. Clinical Trials: Final National Coverage Decision. It has been previously observed that the age-dependent rate in the reduction of deaths attributed to cancer in the United States is correlated with the age-dependent accrual of young adults to national cancer treatment trials during the same era.69 After suicide, cancer is the second leading cause of death due to disease among AYAs. 2004 Aug 25;292(8):922; author reply 922-3. doi: 10.1001/jama.292.8.922-a. Institute of Medicine. A promising tool to foster informed consent. A number of factors have been found to deter physician recommendation for trial participation. Accrual proportion (%) was estimated from cancer incidence in SEER 9 regions and population data from the U.S. Census Bureau.73,75. Concomitantly, cancer has become the most frequent cause of death due to disease in AYAs.68 During the past decade (2000 to 2009), deaths due to cancer declined in all age groups except in young adults age 20 to 29; in 25- to 29-year-olds, deaths due to cancer actually increased.69, FIGURE 2. Fred Hutch's Dr. Joseph Unger, a biostatistician whose research focuses on improving access to trials, led a new study on how comorbidities squelch patient participation -- and what we might be able to do about it. For the SELECT trial, several strategies specifically addressed patients with low socioeconomic status.61,62 SELECT provided funds to sites semiannually to offset travel expenses and meals, in addition to providing patient retention items. Paper presented at: 23rd Society of Clinical Research Associates Annual Meeting; September 2014; Orlando, FL. As shown in Fig. Descriptive statistics will be summarized and the blood and tissue marker data will be correlated with clinical endpoints (response, DCR12, duration of response, OS, PFS, adverse events, etc.). Availability may be affected by local religious customs concerning contraceptive studies and ethical guidelines limiting pediatric clinical trials. Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: a retrospective analysis of the Know Your Tumor registry trial. Permissions, Authors May 19, 2016. The red bars indicate the adolescent and young adult (AYA) age group. This is unfortunate given the frequency with which the direct and indirect costs of trial participation have been cited as meaningful barriers.41 Two recent articles overcame this limitation. Enrollment to the trial occurred from 2007 through 2011 and reached full accrual of 1,513 patients, indicating a highly successful recruitment effort. The Office of the Inspector General has released guidance regarding the use of clinical trial websites, indicating that IRB approval of a clinical trial listing, if limited to selected basic information, is not required.108, InVentiv Health, a contract research organization, has provided specific plans to assist researchers to plan digital recruitment campaigns (Table 2).109 Their plans are premised on the idea that recruitment for global clinical trials is an area ripe for re-engineering. Crucially, increased accrual to trials is important for patients because trials provide patients the opportunity to receive the newest treatments. 10.Pishvaian MJ, Blais EM, Brody JR, et al. Epub 2007 Aug 8. Efforts to improve trial enrollment of cancer patients are clearly needed. The literature indicates that structural barriers preclude patient participation in trials for half of all cancer patients. More is needed to overcome the national AYA cancer-related death problem, beginning with increased clinical trial availability, access, referrals, participation, and conduct. Finally, increased accrual to trials is important for patients, because trials provide opportunity to receive the newest treatments. However, trials are often criticized for having eligibility criteria that are too narrow, sacrificing generalizability.26 These exclusions also make trials less accessible for patients. Methods: A total of 158 women were treated for ovarian cancer at a regional cancer center. Incorporate error reduction strategies and consider regional variations in the standards of care and their effect on trial results. In comparison to whites, after adjusting for age, cancer type, and sex, patients enrolled in 2000 through 2002 were 24% less likely to be black (adjusted relative risk ratio, 0.76; 95% CI, 0.65-0.89; P<.001). In this article, we attempt to characterize the specific barriers to cancer clinical trial participation. In the United States, the practice of paying patients for trial participation is widespread, but also contentious, highly variable, and lacking in general guidance.122 One concern is that a payment inducement might alter a subject’s assessment of potential risks or impair their judgment, although there is little evidence that payment inducements do or do not affect assessment.123,124 A careful calibration of the size of any monetary incentive would be necessary to avoid undue influence.125, Measures to address socioeconomic disparities in recruitment may have a preferentially beneficial impact on minority patients. A better approach may be to grow and engage your audience first, before patients are recruited.110, TABLE 2. Even if a trial is available, patients may not be eligible. It has been consistently estimated that less than 5% of adult patients with cancer enroll in cancer clinical trials. These additional funds were most commonly used to provide additional staff time for minority recruitment. Implement risk-based monitoring and clinical inspection. 2006 Feb;3(2):e19. Clinical trial accrual to cancer case ratios were evaluated using a database of residents at the continental United States seen at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins from 2005 to 2007. Age-, sex-, and race-based differences among patients enrolled versus not enrolled in acute lung injury clinical trials. How do doctors explain randomised clinical trials to their patients? (2000-2010). Relationships are self-held unless noted. Kaposi sarcoma is excluded due to the HIV/AIDS epidemic during the 1980s and early 1990s; thyroid cancer is excluded because of overdiagnosis and increasing survival inflation. Data source is SEER 9 regions.75. Viewed in this light, the issue of clinical trial enrollment is foundational, lying at the heart of the cancer clinical trial endeavor. Lara et al prospectively tracked barriers to cancer clinical trials at the University of California (UC) Davis Cancer Center from 1997 to 2000.20 Among patients considered for trial availability, there was no trial available to 47% of patients (Table 1). A prior study of the effect of the 2000 Medicare policy change on trial participation found that patients with Medicare plus private insurance participated at a higher rate following the policy change, whereas patients with Medicare alone participated at rates similar to those prior to the policy change.53 This finding points to the prohibitive influence of copays and coinsurance for some patients. Advertisers, Journal of Clinical Oncology Thus, trial results must generalize to nontrial patients, at least to some degree. Cancer.Net, ASCO.org The National Cancer Institute’s (NCI) cooperative group clinical trial treatment program caps enrollment for its funded groups at 17,000 total patients per year, representing 1% of the estimated 1.7 million new cancer diagnoses in the United States in 2015.4, 5, To understand the effect of clinical trial participation on cancer population mortality and survival, one might imagine a counterfactual system in which the cancer clinical trial participation rate was much higher. Diversity Awareness and Documentation Practices Among Oncology Advanced Practice Providers. Despite the importance of diversity of cancer trial participants with regard to race, ethnicity, age, and sex, there is little recent information about the representation of these groups in clinical trials. U.S. Food and Drug Administration. Engage and recruit clinical research participants. In the authors’ view, the globalization of clinical research “is vital to speed up availability of life-saving medicines throughout the world.”99 In the setting of a domestic clinical trial system that has been described as being in a state of crisis, this view has added weight.12. In the view of Barrios et al, the globalization of clinical trial research is unavoidable.99 In a wide ranging review, they propose the following solutions to some of the challenges of clinical trial globalization: Harmonize and share standards and goals for product safety, quality, and efficacy. If a trial is available, an evaluation of trial eligibility is made, and, if eligible, a trial is discussed with the patient. Fewer than one in 20 adult patients with cancer enroll in cancer clinical trials. Kantor O, Chang C, Yao K, Boughey J, Roland C, Francescatti AB, Blair S, Dickson Witmer D, Hunt KK, Nelson H, Weiss A, Oseni T. Ann Surg Oncol. Therefore, a thorough understanding of the nature of trial enrollment patterns and barriers to enrollment is of paramount importance. The proportion of trial participants who are black has declined in recent years. Am Soc Clin Oncol Educ Book 2016;35:185-98.  |  A prospective pilot study, Comparison of toxicity experienced by older versus younger patients enrolled in breast cancer clinical trials, Chemotherapy in the oldest old: the feasibility of delivering cytotoxic therapy to patients 80 years old and older, Use of comprehensive geriatric assessment in older cancer patients: recommendations from the task force on CGA of the International Society of Geriatric Oncology (SIOG), Comprehensive geriatric assessment for older patients with cancer, Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: a systematic review, Identifying an accurate pre-screening tool in geriatric oncology, Detecting disabilities in older patients with cancer: comparison between comprehensive geriatric assessment and vulnerable elders survey-13, Assessment and treatment of elderly patients with cancer, Payment of research subjects involved in clinical trials is unethical, An analysis of U.S. practices of paying research participants, The scientific impact of positive and negative phase 3 cancer clinical trials, In and out, good and bad news, of generalizability of SWOG treatment trial results, American Society of Clinical Oncology Educational Book, http://www.cancer.gov/research/areas/clinical-trials/nctn/budget#1, https://www.cms.gov/Medicare/Coverage/ClinicalTrialPolicies/downloads/finalnationalcoverage.pdf, http://www.census.gov/popest/data/intercensal/national/nat2010.html, https://clinicaltrials.gov/ct2/show/NCT02043587?term=acute+lymphoblastic+leukemia+wieduwilt&rank=1, http://www.pharmoutsourcing.com/Featured-Articles/150621-Key-Strategies-for-Effective-Globalization-of-Clinical-Trials/, https://www.ucdmc.ucdavis.edu/biorepositories/pdfs/misc-biobank/Top-considerations-for-using-social-media-in-research.pdf, www.fda.gov/regulatoryinformation/guidances/ucm126428.htm, http://oig.hhs.gov/oei/reports/oei-01-97-00198.pdf, http://www.inventivhealth.com/docs/e-Recruiting_Using_Digital_Platforms_Social_Media_and_Mobile_Technologies_to_Improve_Clinical_Trial_Enrollment.pdf, http://www.hhs.gov/ohrp/humansubjects/commonrule/, Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update, Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline, Prognostic Index for Acute- and Lymphoma-Type Adult T-Cell Leukemia/Lymphoma, Reasons to Reject Physician Assisted Suicide/Physician Aid in Dying, Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2−, Node-Positive, High-Risk, Early Breast Cancer (monarchE), Integration of Palliative Care Into Standard Oncology Care: American Society of Clinical Oncology Clinical Practice Guideline Update, Patient-Clinician Communication: American Society of Clinical Oncology Consensus Guideline, Updating the American Society of Clinical Oncology Value Framework: Revisions and Reflections in Response to Comments Received, American Society of Clinical Oncology Statement: A Conceptual Framework to Assess the Value of Cancer Treatment Options, Symptom Monitoring With Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Figure 3 shows the relationship between the average percent change (APC) in the 5-year cancer-specific survival rate from 1985 to 1999 and the accrual rate to national cancer treatment trials during 2001 to 2006. OBJECTIVE: To characterize the representation of racial/ethnic minorities, women, and older persons among participants in surgical trials sponsored by the National Cancer Institute (NCI). Second, the dependency of survival prolongation on treatment trial accrual has been apparent for all ages. The survival disparity between AYAs and other patients may be due in part to early achievements in improving survival for AYAs, after which resources were directed toward research in other age groups. ASCO Connection USA.gov. Inevitably, the decision about whether to participate in a trial will reflect a patient’s personal preferences, which may also be influenced by family and friends.38, Some proportion of patients are influenced by altruistic motivations.15 However, the majority of patients are (appropriately) concerned primarily with finding the best possible treatment of their disease.15,39,40 In the absence of other barriers, a patient who believes that the best possible treatment option is to be found in a clinical trial is more likely to participate in that clinical trial.33, Patients have frequently reported being uneasy or fearful about the prospect of participating in a clinical trials.41 In some cases this could be due to a residual mistrust of medical science due to past abuses, such as the infamous Tuskegee Syphilis Study or the history of human experimentation with radiation following World War II.42,43 Attention in the last several decades to the process of rigorous consent may have reduced these fears, especially for younger generations of patients. Figure 6 also shows the 5-year leukemia-specific survival rate for patients with ALL as a function of single year of age. Accrual data from the National Cancer Institute Cancer Therapy Evaluation Program (CTEP) were provided by Steve Friedman, Michael Montello, Troy Budd, and Samantha Finnegan via the Freedom of Information Act. The answer to this question is crucial, because if trial participation is ultimately unrelated to cancer population survival gains, the issue of barriers to trial participation has little importance. In a separate analysis, the ethnic distribution of patients enrolled in 2000 through 2002 was compared with those enrolled in 1996 through 1998, using logistic regression models to estimate the relative risk ratio of enrollment for racial and ethnic minorities to that of white patients during these time periods. Institute of Medicine. 2021 Jan 22:1-13. doi: 10.1007/s40487-021-00140-w. Online ahead of print. Top considerations for using social media in research—it all starts with a plan. CancerLinQ We have categorized barriers to trial participation as structural (especially the absence of an available clinical trial), clinical (i.e., not meeting eligibility), attitudinal (with respect to both patients and physicians), and demographic and socioeconomic. Accrual proportion (%) was estimated from cancer incidence in SEER 9, SEER 13, and SEER 18 regions and population data from the U.S. Census Bureau.73,75-77. Chen MS Jr, Lara PN, Dang JH, Paterniti DA, Kelly K. Cancer. 2020 Dec 8;11(12):1471. doi: 10.3390/genes11121471. The most consistent and largest disparity pertains to age.1,15,50-53 Hutchins et al found that patients in cooperative group trials were much less likely to be age 65 or older than those in the U.S. cancer population.50 Some evidence suggests that attitudinal barriers on the part of physicians play a role.13,54-56 In addition, older patients are likely to have more comorbid burdens, inducing clinical exclusions.57,58 To the extent that trials seek to reflect the population of patients for whom new trial-proven treatments will be administered, better representation of older patients in trials is critical. Patients have exposures to study drugs with potential or realized adverse events. The entire age range that was accessible on many cancer websites such as the agent linking patients to cancer. 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