Michael Montello

Participation of Patients 65 Years of Age or Older in Cancer Clinical Trials

PURPOSE Although 61% of new cases of cancer occur among the elderly, recent studies indicate that the elderly comprise only 25% of participants in cancer clinical trials. Further investigation into the reasons for low elderly participation is warranted. Our objective was to evaluate the participation of the elderly in clinical trials sponsored by the National Cancer Institute (NCI) and assess the impact of protocol exclusion criteria on elderly participation. PATIENTS AND METHODS We conducted a retrospective analysis using NCI data, analyzing patient and trial characteristics for 59,300 patients enrolled onto 495 NCI-sponsored, cooperative group trials, active from 1997 through 2000. Our main outcome measure was the proportion of elderly patients enrolled onto cancer clinical trials compared with the proportion of incident cancer patients who are elderly. RESULTS Overall, 32% of participants in phase II and III clinical trials were elderly, compared with 61% of patients with incident cancers in the United States who are elderly. The degree of underrepresentation was more pronounced in trials for early-stage cancers than in trials for late-stage cancers (P <.001). Furthermore, protocol exclusion criteria on the basis of organ-system abnormalities and functional status limitations were associated with lower elderly participation. We estimate that if protocol exclusions were relaxed, elderly participation in cancer trials would be 60%. CONCLUSION The elderly are underrepresented in cancer clinical trials relative to their disease burden. Older patients are more likely to have medical histories that make them ineligible for clinical trials because of protocol exclusions. Insurance coverage for clinical trials is one step toward improvement of elderly access to clinical trials. Without a change in study design or requirements, this step may not be sufficient.

Adolescents and young adults with cancer : The scope of the problem and criticality of clinical trials

In the U.S., older adolescents and young adults with cancer have benefited less from therapeutic advances than did either younger or older patients. One factor that may explain this deficit is the relative lack of participation of patients in this age group on clinical trials of therapies that could improve their outcome. Comparisons were made of the participation of cancer patients on clinical trials in the U.S., as a function of patient age, with the change in national cancer mortality rate; and Surveillance, Epidemiology, End Results (SEER) cancer survival rate as a function of age. The participation rate in cancer treatment trials has been strikingly lower in 15–34‐year‐olds than in younger or older patients. The nadir has been apparent for both males and females in all of the major ethnic and racial groups. The national cancer mortality reduction and SEER survival improvement shows a similar age dependence. In the U.S., the age‐dependence of cancer treatment trial participation, and of improvement in survival prolongation and cancer death rates, are correlated. Regardless of whether there is a causal relationship, the impact on the older adolescent and young adult U.S. population is substantial, adversely affecting the national cost of healthcare, the person‐years of life lost, the loss of young people entering the job market, and the scientific knowledge and social implications of cancer during adolescence and early adulthood. National initiatives are underway to address these issues, with special emphasis on increasing the availability and access to clinical trials designed for older adolescents and young adults. Cancer 2006.

National survival trends of young adults with sarcoma: lack of progress is associated with lack of clinical trial participation.

Young adults with cancer in the U.S. have had less improvement in survival than either younger patients or older patients. The authors attempted to determine whether similar deficits have occurred in young adults with sarcomas and, if so, then why.

The challenges of clinical trials for adolescents and young adults with cancer.

In the United States, Europe, and Australia, and probably all countries of the world, older adolescents and young adults with cancer are under‐represented in clinical trials of therapies that could improve their outcome. Simultaneously, the survival and mortality rates in these patients have mirrored the clinical trial accrual pattern, with little improvement compared with younger and older patients. This suggests that the relative lack of participation of adolescent and young adult patients in clinical trials has lessened their chances for as good an outcome as that enjoyed by patients in other age groups. Thus, increased availability of and participation in clinical trials is of paramount important if the current deficits in outcome in young adults and older adolescents are to be eliminated. Regardless of whether there is a causal relationship, the impact of low clinical trial activity on furthering our scientific knowledge and management of cancer during adolescence and early adulthood is detrimental. Pediatr Blood Cancer 2008:50:1101–1104.

Stakeholder perspectives on implementing the National Cancer Institute’s patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

The National Cancer Institute (NCI) is developing a patient-reported version of its Common Terminology Criteria for Adverse Events, called the “PRO-CTCAE.” The PRO-CTCAE consists of a library of patient-reported items which can be administered in clinical trials to directly capture the patient experience of adverse events during cancer treatment, as well as a software platform for administering these items via computer or telephone. In order to better understand the impressions of stakeholders involved in cancer clinical research about the potential value of the PRO-CTCAE approach to capturing adverse event information in clinical research, as well as their perspectives about barriers and strategies for implementing the PRO-CTCAE in NCI-sponsored cancer trials, a survey was conducted. A survey including structured and open-ended questions was developed to elicit perceptions about the use of patient-reported outcomes (PROs) for adverse event reporting, and to explore logistical considerations for implementing the PRO-CTCAE in cancer trials. The survey was distributed electronically and by paper to a convenience sample of leadership and committee members in the NCI’s cooperative group network, including principal investigators, clinical investigators, research nurses, data managers, patient advocates, and representatives of the NCI and Food and Drug Administration. Between October, 2008 through February, 2009, 727 surveys were collected. Most respondents (93%) agreed that patient reporting of adverse symptoms would be useful for improving understanding of the patient experience with treatment in cancer trials, and 88%, 80%, and 76%, respectively, endorsed that administration of PRO-CTCAE items in clinical trials would improve the completeness, accuracy, and efficiency of symptom data collection. More than three fourths believed that patient reports would be useful for informing treatment dose modifications and towards FDA regulatory evaluation of drugs. Eighty-eight percent felt that patients in clinical trials would be willing to self-report adverse symptoms at clinic visits via computer, and 68% felt patients would self-report weekly from home via the internet or an automated telephone system. Lack of computers and limited space and personnel were seen as potential barriers to in-clinic self-reporting, but these were judged to be surmountable with adequate funding. The PRO-CTCAE items and software are viewed by a majority of survey respondents as a means to improve adverse event data quality and comprehensiveness, enhance clinical decision-making, and foster patient-clinician communication. Research is ongoing to assess the measurement properties and feasibility of implementing this measure in cancer clinical trials.

Young adults with leukemia in the United States: Lack of clinical trial participation and mortality reduction during the last decade

6623 Background: Young adults with cancer have been found to have had less survival prolongation and mortality rate reduction than either younger or older patients (Proc. ASCO 21: 389a, 2002). We attempted to determine if this observation applied to young adults with leukemia and if so, why. METHODS National leukemia mortality rates during 1990-2000 were obtained from the National Center for Health Statistics. The incidence of leukemia during 1993-1999 was obtained in 4,214 1-44 year-olds (yo) from the U.S. SEER program (courtesy of L. Ries). To estimate national progress in reducing the mortality rate from leukemia relative to changes in its incidence, a relative survival rate index (RSR) was derived from the ratio of the mortality rate to incidence: 1 -[mortality rate:incidence]. National leukemia trial data were obtained on 14,087 <45 yo on cooperative group treatment trials during 1997-2002. RESULTS Above age 15, the clinical trial participation and survival rates co-declined precipitously for leukemia of all types, for acute lymphoblastic leukemia (ALL) and for acute myeloid leukemia (AML). Compared with <15 yo, 20-44 yo accrued to national treatment trials at 91-96%, 96-99%, and 61-82% lower rates, respectively, for all leukemia (Table), ALL and AML. For all leukemia, the RSR was 33-37% lower among 15-44 yo than in 1-15 yo (Table). For ALL, the RSR was 45-69% lower among 20-44 yo than among 1-15 yo. Corresponding values for AML were 35-46%. The RSR was significantly correlated with the national trial accruals: p < .0001, .001 and .01 for all leukemia, ALL and AML, respectively. CONCLUSIONS A relative lack of progress in improving the outcome of young adults with leukemia appears to be due to their underrepresentation on clinical trials. Reversing the deficit will require broad support and collaboration to increase clinical trial availability, access, and participation. [Figure: see text] No significant financial relationships to disclose.

Readability and compliance of NCI's informed consent documents (ICDs) with its revised ICD template.

e18162Background: Since 1997, NCI has used a standardized template to develop ICDs for its clinical trials. In 2013 NCI launched a revised template seeking to reduce the length and complexity of it...