Underrepresentation In Clinical Trials Research Articles

Antiretroviral Treatment Efficacy and Safety in Older HIV-Infected Adults.

Highly active antiretroviral therapy (ART) and its widespread availability have revolutionized the landscape of HIV care and patient outcomes, transforming infection with HIV into a manageable chronic condition rather than a life-limiting disease. This transformation has created an older patient demographic. The effect that older age has on the outcomes of ART is not completely understood. Limited data are available in older individuals due to underrepresentation in clinical trials. To better understand this relationship, we conducted a literature search to assess the impact of older age on the outcomes of ART in the older HIV-infected population, including immunologic and virologic outcomes, mortality, disease progression, toxicity of ART, and pharmacokinetic considerations. In addition, package inserts of antiretroviral (ARV) medications were reviewed for efficacy, safety, and pharmacokinetic information pertaining to the older population. Most studies in older adults (50yrs or older) demonstrated slower and blunted CD4 immune recovery but better virologic suppression in response to ART. Higher rates of mortality and faster disease progression have been observed in adults 50 years and older, particularly during the first year after ART initiation. HIV-infected patients aged50years and older appear to be at greater risk for certain ART-associated toxicities including nephrotoxicity, decline in bone mineral density and bone fracture, symptomatic peripheral neuropathy, and cardiovascular disease including myocardial infarction. The available literature suggests that clinicians should consider avoiding agents such as tenofovir disoproxil fumarate (TDF) in older patients with risk factors for renal impairment and/or osteoporosis. If TDF is used in patients aged50years or older, more frequent monitoring should be considered. Older age was a significant predictor for higher atazanavir exposure and higher lopinavir trough concentration at 24weeks. The clinical implications of these findings are unknown. It is imperative that future development of novel ARV drug therapies includes a greater proportion of older subjects in clinical trials.

Defining the Issues in the Treatment of Elderly Patients With Advanced Non-Small-Cell Lung Cancer

SUMMARY Elderly patients constitute a substantial proportion of patients with advanced NSCLC. Several unresolved issues surround the treatment of elderly patients with NSCLC, including under-representation in clinical trials, the definitions of fit and unfit patients and the appropriate age cut-off for this population. Taken together, these factors have a large impact on the treatment of elderly patients with advanced NSCLC. An urgent need exists to develop new strategies for clinical trial design that may lead to improved outcomes in these patients. This review will address the existing barriers and controversies in the management of advanced NSCLC in the elderly, focusing on cytotoxic chemotherapy regimens. Results of clinical trials conducted in the elderly and those from planned subset analyses for age-unspecified trials will be provided, with a focus on recently reported studies. Outcomes from population databases reporting on this population in a nonclinical trial setting will be reviewed.

Abstract C44: Gender disparities in documentation of fertility risks among adolescents and young adults with cancer

Abstract Introduction: The Adolescent and Young Adult (AYA) community is an underserved population due to their unique quality of life and late-effect issues not experienced in pediatric or older groups as well as their under-representation in clinical trials. One issue of particular concern to the AYA population is future fertility. For almost a decade the American Society for Clinical Oncology (ASCO) has identified and supported the need for oncologists to discuss fertility preservation with patients of reproductive age The updated 2013 ASCO guidelines expand the role of the physician to not only discuss fertility, but also to document this discussion in the medical record. This study sought to establish the existing rate of documentation of risk of infertility, discussion of fertility preservation options, and referrals to fertility specialists in AYA patients' medical records at three National Cancer Institute (NCI) Designated Comprehensive Cancer Centers who had received the FertileHope Center of Excellence award. As a secondary aim, the study examined whether documentation rates for each of these outcomes varied by institution, patient gender, or cancer site. Methods: Each of the three sites reviewed a randomized, stratified selection of patient charts within each of the four disease sites most common in AYA populations (breast cancer, leukemia/lymphoma, sarcoma, and testicular cancer). Patient charts were eligible for review as part of the current study if they included new patients who: a) were diagnosed in 2011 with no prior gonadotoxic therapy; b) were between 18 and 45 years of age; c) did not have multiple primary cancers; and d) were not seen at the cancer center only as a second opinion or consultation. Quality Oncology Practice Initiative (QOPI) methods were used to collect evidence related to documentation of: a) discussion of risk of infertility; b) discussion of fertility preservation options; c) referral to a fertility specialist; or d) that a, b, c was not needed or was declined by patient). Results: A total of 229 charts were abstracted among three cancer institutes A, B, and C, with 75 charts abstracted from breast, 76 from lymphoma/leukemia, 51 from sarcoma, and 27 from testicular. One hundred thirty (57%) abstracted charts were female patients. Overall, 31% of patient charts documented discussion of fertility risk, 25% documented discussion of fertility preservation options, and 14% documented referral to a fertility specialist. Documentation of discussion of fertility risk was differentially distributed by gender (p=0.009) and institute (p < 0.0001). Documentation of fertility preservation options discussion was differentially distributed by gender (p= 0.002), diagnosis (p = 0.001), and institute (p = 0.017). Conclusion: The rate of documentation of discussion of fertility risk prior to initiation of therapy among AYA patients is low, particularly among women. In addition, documentation of fertility preservation options discussion was low among women with breast cancer. While greater numbers of discussions may be occurring, it is difficult to create interventions that may help meet this critical need for this underserved group without documentation in the medical record. Rates may improve with increased provider education and other national and local intervention efforts to raise awareness. Citation Format: Ivana Sehovic, Rebecca Block, Marla L. Clayman, Susan Eggly, Brandon Hayes-Lattin, Joanne Kelvin, Ji-Hyun Lee, Joyce Reinecke, Susan T. Vadaparampil, Gwendolyn P. Quinn. Gender disparities in documentation of fertility risks among adolescents and young adults with cancer. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C44. doi:10.1158/1538-7755.DISP13-C44

037 OUTCOME OF 1051 OCTOGENARIANS AFTER PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR ST ELEVATION MYOCARDIAL INFARCTION: OBSERVATIONAL COHORT FROM THE LONDON HEART ATTACK GROUP

IntroductionThe use of primary percutaneous coronary intervention (PCI) in octogenarians to treat ST elevation myocardial infarction (STEMI) is less than in other age groups. This is due in part to...

Increasing ethnic minority participation in substance abuse clinical trials: Lessons learned in the National Institute on Drug Abuse's Clinical Trials Network.

Underrepresentation in clinical trials limits the extent to which ethnic minorities benefit from advances in substance abuse treatment. The objective of this article is to share the knowledge gained within the Clinical Trials Network (CTN) of the National Institute on Drug Abuse and other research on recruiting and retaining ethnic minorities into substance abuse clinical trials. The article includes a discussion of two broad areas for improving inclusion-community involvement and cultural adaptation. CTN case studies are included to illustrate three promising strategies for improving ethnic minority inclusion: respondent-driven sampling, community-based participatory research, and the cultural adaptation of the recruitment and retention procedures. The article concludes with two sections describing a number of methodological concerns in the current research base and our proposed research agenda for improving ethnic minority inclusion that builds on the CTN experience.

Examining Sex and Gender Disparities in Total Joint Arthroplasty

Total joint arthroplasty (TJA) is remarkably successful for treating osteoarthritis: most patients see substantial gains in function. However, there are considerable geographic, racial, and gender variations in the utilization of these procedures. The reasons for these differences are complex. We examined sex and gender disparities in TJA. Through Medline/PubMed searches, we identified 632 articles and from these selected 61 for our review. WHERE ARE WE NOW?: A number of factors might explain sex and gender disparities in TJA: underrepresentation in clinical trials, differences in willingness to undergo surgery, pain responses to underlying disease and treatment, patient-physician relationships, treatment preferences, provider-level factors such as physician-patient communication style, and system-level factors such as access to specialist care. Since women have a higher prevalence of arthritis and degenerative joint diseases and overall demand for these procedures will continue to grow, the need to understand why there is a gap in utilization based on gender is imperative. WHERE DO WE NEED TO GO?: Understanding what exactly is meant by "disparity" is essential because it is possible anatomic factors may have different impacts on utilization from cultural factors. Ideally, information about these factors should be integrated into the decision-making process so that patients and providers can make the most informed choice about whether or not to undergo the procedure. HOW DO WE GET THERE?: To better understand all of the potential reasons for how anatomic and cultural factors related to sex and gender might impact decision-making and overall utilization of TJA, more research focusing on these factors must be designed and carried out.

Extremity Soft Tissue Sarcoma Care in the Elderly: Insights into the Generalizability of NCI Cancer Trials

The projected increase in older persons in the United States, their underrepresentation in clinical trials, and the rarity of extremity soft tissue sarcomas (ESTS) limit our understanding of ESTS care in the elderly. We explored the extent of older age (> or =65 years) on patterns of ESTS care in NCI-sponsored population-based dataset. Using the 1991-2006 Surveillance Epidemiology and End Results registries, we identified 2586 Medicare aged persons > or =65 years with ESTS. We compared demographics, tumors, and treatments by age category. Multivariable analyses were used to examine the effect of older age on ESTS care and survival, adjusting for covariates. More than 30% of adult ESTS were diagnosed in patients older than 65 years. A significant trend was observed between increasing age and decreased use of sarcoma-directed surgery and delivery of radiotherapy after limb-sparing surgery for high-grade or T2 tumors. Limb amputation rates did not vary by age. However, both African-American (odds ratio [OR] 1.85, 95% confidence interval [95% CI] 1.05-3.27, P = .0341) and Hispanic races (OR 2.17, 95% CI 1.27-3.70, P = .0044) predicted higher rates of limb amputation than whites. Although our multivariable analyses showed that decreased use of sarcoma-directed surgery was only limited to age 85 + years, it also showed that older age predicted poorer cancer-specific mortality following sarcoma-directed surgery (P < .0001). In this US population-based study, the decreased use of sarcoma-directed surgery in the elderly was only limited to those older than 85 years. The association between older age and increased cancer-related mortality deserves future investigation to carefully examine potential effects of undertreatment.

Clinical Management Update: Evaluation and Management of Older Patients with Breast Cancer

Recent gains in life expectancy, coupled with aging as a risk factor for breast cancer, make breast cancer primarily a disease of older women. Evaluation of the biology of breast cancer according to age has suggested that estrogen receptor-positive, low-S-phase, low-tumor-grade, and human epidermal growth factor receptor 2-negative tumors are more common in older than younger women. However, this has not translated into any major survival advantage for older women with breast cancer over their younger counterparts. Several reasons, including undertreatment and underrepresentation in clinical trials, may account for this age-related disparity. In this brief review, recent practice-changing breast cancer updates of relevance to the care of older patients with breast cancer are discussed and summarized. Because the population is aging and the number of older patients with breast cancer will continue to increase, it is imperative that older patients with breast cancer be encouraged to participate in cutting edge research and that state-of-the-art oncology care be provided to this underserved population.

Geriatric assessment in older patients with breast cancer.

Most cases of breast cancer are diagnosed in older adults. Older women have an increased risk for breast cancer-specific mortality and are at higher risk for treatment-associated morbidity than younger women. However, they are also less likely to be offered preventive care or adjuvant therapy for this disease. Major gaps in evidence exist regarding the optimal evaluation and treatment of older women with breast cancer because of significant underrepresentation in clinical trials. Chronologic age alone is an inadequate predictor of treatment tolerance and benefit in this heterogeneous population. Multiple issues uniquely associated with aging impact cancer care, including functional impairment, comorbidity, social support, cognitive function, psychological state, and financial stress. Applying geriatric principles and assessment to this older adult population would inform decision making by providing estimates of life expectancy and identifying individuals most vulnerable to morbidity. Ongoing research is seeking to identify which assessment tools can best predict outcomes in this population, and thus guide experts in tailoring treatments to maximize benefits in older adults with breast cancer.

Adolescents with cancer in Italy: Entry into the national cooperative paediatric oncology group AIEOP trials

PurposeSurvival of adolescents (15–19 years old) with cancer has shown less favourable improvement in comparison with survival rates for younger children and older adults. This might be partly explained by the relative lack of participation of adolescents in cooperative clinical protocols. MethodsThis analysis compares the number of 15- to 19-year-olds treated at the paediatric oncology centres affiliated to the AIEOP (and registered in the ‘model 1.01’) with the number of incident cases predicted in Italy based on incidence rates from the Italian network of cancer registries (AIRTum). ResultsBy 2006, over 22,000 cases had been registered in the model 1.01, and 1743 of these were adolescents. The ratio of observed/expected (O/E) cases of 15- to 19-year-olds was 0.10 (as opposed to 0.77 for the 0–14-year-old children), and this ratio increased from 0.05 to 0.18 over three successive study periods (1989–1994, 1995–2000 and 2001–2006). Sarcomas were the neoplasms with the highest O/E ratios, with 0.28 and 0.43 for osteosarcoma and Ewing sarcoma and 0.33 and 0.39 for rhabdomyosarcoma and other soft-tissue sarcomas, respectively. In the period 1989–2006, 55% of the adolescents registered (versus 69% of the children) were enrolled in formal national trials. ConclusionOur study confirms a lower referral of 15- to 19-year-old adolescents to paediatric oncology units and their under-representation in clinical trials, but we also observed a progressive improvement in this situation in recent years.

Recruitment and retention of low-income minority women in a behavioral intervention to reduce smoking, depression, and intimate partner violence during pregnancy

BackgroundResearchers have frequently encountered difficulties in the recruitment and retention of minorities resulting in their under-representation in clinical trials. This report describes the successful strategies of recruitment and retention of African Americans and Latinos in a randomized clinical trial to reduce smoking, depression and intimate partner violence during pregnancy. Socio-demographic characteristics and risk profiles of retained vs. non-retained women and lost to follow-up vs. dropped-out women are presented. In addition, subgroups of pregnant women who are less (more) likely to be retained are identified.MethodsPregnant African American women and Latinas who were Washington, DC residents, aged 18 years or more, and of 28 weeks gestational age or less were recruited at six prenatal care clinics. Potentially eligible women were screened for socio-demographic eligibility and the presence of the selected behavioral and psychological risks using an Audio Computer-Assisted Self-Interview. Eligible women who consented to participate completed a baseline telephone evaluation after which they were enrolled in the study and randomly assigned to either the intervention or the usual care group.ResultsOf the 1,398 eligible women, 1,191 (85%) agreed to participate in the study. Of the 1,191 women agreeing to participate, 1,070 completed the baseline evaluation and were enrolled in the study and randomized, for a recruitment rate of 90%. Of those enrolled, 1,044 were African American women. A total of 849 women completed the study, for a retention rate of 79%. Five percent dropped out and 12% were lost-to-follow up. Women retained in the study and those not retained were not statistically different with regard to socio-demographic characteristics and the targeted risks. Retention strategies included financial and other incentives, regular updates of contact information which was tracked and monitored by a computerized data management system available to all project staff, and attention to cultural competence with implementation of study procedures by appropriately selected, trained, and supervised staff. Single, less educated, alcohol and drug users, non-working, and non-WIC women represent minority women with expected low retention rates.ConclusionWe conclude that with targeted recruitment and retention strategies, minority women will participate at high rates in behavioral clinical trials. We also found that women who drop out are different from women who are lost to follow-up, and require different strategies to optimize their completion of the study.

Survey of oncologists' perceptions of barriers to accrual of older patients with breast carcinoma to clinical trials.

Prior research has documented the under-representation in clinical trials of older patients with cancer. In part of a larger study to test the magnitude of these barriers to entering eligible older patients with carcinoma of the breast into clinical trials (Cancer and Leukemia Group B [CALGB] trial 9670), barriers to accruing eligible older patients to clinical trials were obtained from the physician's perspective. One hundred fifty-six physicians (85% oncologists) who treated patients with breast carcinoma at 10 CALGB institutions completed a questionnaire concerning what they perceived as barriers to enrolling older patients with breast carcinoma on clinical trials and possible interventions that may improve accrual. Physicians' perceptions of the most important barriers to accrual of older patients were: 1) elderly patients have significant comorbid conditions that are not excluded by the protocol but that may affect how they would respond to treatment (16%); elderly patients have difficulty understanding what is required in a complicated treatment trial, resulting in poor compliance (16%); treatment toxicity (14%); and elderly patients often do not meet the eligibility criteria (15%). Oncologists most frequently suggested that the most effective interventions for improving the accrual of elderly patients to trials included making personnel available in the clinic to explain clinical trials to older patients and their families (25%) and providing physicians with educational materials concerning treatment toxicity in the elderly (18%). Physicians viewed barriers to accruing older patients with breast carcinoma to clinical trials as multidimensional, with the most important involving protocol requirements, treatment specific issues, and older patients' medical and cognitive characteristics. Thus, a variety of interventions would be needed to improve accrual of older patients to clinical trials, including increasing physicians' knowledge concerning treatment toxicity in the elderly, simplifying protocol requirements, and reducing treatment toxicity.

Ethical implications of women’s underrepresentation in clinical trials

Excluding women from participating in clinical drug trials might seem like a good thing. It may seem like a good way to protect women from the risks of being a research subject and a way to prevent fetal harm. However, the exclusion or inadequate representation of women in clinical trials may actually cause harm. Excluding women from clinical trials does not rule out the possibility of damage to offspring. Nor does it guarantee researchers or institutions freedom from legal liability. The issue of women’s exclusion has received substantial attention in the USA but very little in Australia.

Representation of American Blacks in Clinical Trials of New Drugs

Investigations that have revealed racial differences in drug response and disposition indicate the need for adequate representation of racial minorities in clinical drug trials. There is concern, however, that there may be a disproportionate use of racial and ethnic minorities in clinical research due to the inner city location of most university hospitals. To examine this issue, we reviewed the representation of American blacks in 50 recently published clinical trials of new drugs. This survey revealed that investigators do not seem to adequately take into account racial differences as a potential source of variability. It also was found that in the majority of studies, the proportion of black subjects is less than their proportion in the general population. This underrepresentation in clinical trials suggests that insufficient data exist to accurately assess the safety and efficacy of many new drugs in American blacks.