We searched PubMed, Embase, and the internet for articles in English published from inception to Dec 10, 2013. Search criteria included “age eligibility”, “age eligibility criteria” and “cancer clinical trials”, “age eligibility criteria and cancer”, “age eligibility criteria and origins”, “age eligibility criteria and barriers”, “age eligibility criteria and access”, “age eligibility criteria and adolescent/s”, “age eligibility”, and “cancer trials”.
ReviewAvailable, accessible, aware, appropriate, and acceptable: a strategy to improve participation of teenagers and young adults in cancer trials
Introduction
The global incidence of cancer in teenagers and young adults, when defined as those aged between 15–29 years, is about 350 000 cases per year, less than 3% of the 14·2 million new cases of cancer noted every year.1, 2 However, the global burden of cancer in young people is more significant than these numbers suggest and is often overlooked. Even in developed countries with sophisticated health-care systems, cancer is the leading cause of death from disease for people younger than 39 years.1 When treatment is successful, returns for society are potentially long lasting and economically beneficial. However, cancers in young people are generally not included in prevention, cure, and cancer control initiatives.
There is no universal consensus for the definition of young adulthood. Recommendations for the provision of health care in Canada apply an upper age limit of 29 years; the US National Cancer Institute has extended their definition to younger than 40 years.1 In the UK, teenagers and young adults are individuals aged 15–24 years at diagnosis, which is related to the organisation and commissioning of clinical services for young people in the UK.3 Despite variation in definitions of young adulthood,1 a common finding has emerged from high-income countries with advanced health-care infrastructure: survival gains made over the past 20 years seem to be lower for teenagers and young adults with cancer than those seen for children and older adults.4, 5, 6 This survival deficit has been attributed to several factors, including complex pathways to diagnosis, unique patient and cancer biology, effects of place of care, inappropriate treatment protocols, and poorer rates of participation in clinical trials.5, 7, 8, 9 Lower accrual of teenagers and younger adults in trials than that of children and older adults has now been reported in Australia, Canada, Italy, the UK, and the USA.5, 10, 11, 12, 13, 14, 15
Increasing international attention has been paid to cancer in young people over the past decade, and it is emerging as a distinct specialty that has initiatives designed to improve quality of care and outcomes.2, 16, 17, 18, 19 For many countries, this focus includes health-care policy directives to increase participation of young people in clinical trials for cancer. In the UK, inclusion of patients with cancer in high-quality randomised trials is embedded in health-care service provision. A national network for cancer research supports the running of research studies through the National Health Service. For young people aged 13–24 years, this inclusion is underpinned by guidance3 released by the National Institute for Health and Clinical Excellence in 2005 that included the statement “All children and young people with cancer should be offered entry to any clinical research trial for which they are eligible”. In addition, the National Cancer Research Institute's Teenage and Young Adult Clinical Studies has a national remit to increase the participation of young people in clinical trials for cancer.20 The UK's record in improving trial accrual rates for patients with cancer has been acknowledged to be excellent.21 The National Cancer Research Networks, established in 2001, were given an initial remit to double accrual rates in 3 years from a benchmark of 3·5%. By 2006, about 14% of patients with cancer participated in cancer trials, attesting to the combination of policy, advocacy, and commitment from clinical and research staff within the National Health Service.21 Despite this impressive record and specific policy directives for young people, accompanied by universal free access to health care and research, deficits, when compared with children, persist in participation rates for teenagers and young adults in Great Britain.12
The ambition to include all patients in a clinical trial has been pioneered by the paediatric cancer community in which, historically, as many as 80% of children have been enrolled into trials, a result of a highly coordinated centralised approach to paediatric cancer care and research.22 This high enrolment is believed to have been a major factor contributing to improvements in survival for childhood cancer, which have increased from about 40% in the 1970s to more than 80%.6
International inequalities exist in access to cancer research, the most obvious being the lack of health-care infrastructure in low-to-middle income countries. Nevertheless, in high-income countries, under-represented groups in clinical trials for cancer are well described and include ethnic minority populations, people of low socioeconomic status, elderly patients, and young people.5, 10, 12, 14, 23, 24, 25, 26, 27, 28 A conceptual framework exists describing barriers to recruitment of under-represented populations to cancer clinical trials.27 Here, we consider this framework and its applicability to the recruitment of teenagers and young adults to cancer trials.
Section snippets
Methods
To determine underlying trends in teenager and young adult clinical trial enrolment, we systematically analysed 6 years (from April 1, 2005, to March 31, 2011) of enrolment data from cancer trials in Great Britain for leukaemias, lymphomas, male germ-cell tumours, bone and soft-tissue sarcomas, and brain and CNS tumours (these cancer types account for about two-thirds of cancer incidence in teenagers and young adults).29 We compared accrual rates for children, teenagers and young adults, and
Clinical trial enrolment
Between 2005 and 2010, 9389 (14%) of 68 275 patients aged 0–59 years who were newly diagnosed with selected cancer types were enrolled in one of 49 trials (appendix pp 1–6). Trial participation decreased for patients aged 15 years and older (figure 1A). For the cancer types that we analysed, 1547 (62%) of 2484 patients aged 0–4 years entered trials, falling to 917 (55%) of 1683 patients aged 5–9 years, 852 (44%) of 1958 patients aged 10–14 years, 850 (30%) of 2860 patients aged 15–19 years, and
The five As framework
The need for, and benefit from, greater awareness of trials would not only benefit patients, but might also be important for professionals involved in every level of trial development. As part of the remit for our national group to increase rates of trial participation for young people, we have reached out to relevant stakeholders including paediatric and adult health-care professionals, funders, and policy makers.21 This effort has included enabling discussions between different groups of
Conclusions and recommendations
Investigators have most often described attrition in accrual as occurring for young people older than 15 years.4, 10, 12, 14, 23, 50, 51, 52 We have shown that, for trials with rational criteria for age eligibility either at study outset or through later amendment, the fall in accrual does not occur until after age 19 years, supporting evidence for age-related trial entry criteria having a large effect on recruitment of patients (figure 1). In 2008 we reported under-representation of teenagers
Search strategy and selection criteria
For the website of the National
References (55)
Older adolescents with cancer in North America deficits in outcome and research
Pediatr Clin North Am
(2002)- et al.
Adolescents with cancer in Italy: entry into the national cooperative paediatric oncology group AIEOP trials
Eur J Cancer
(2009) - et al.
Improving recruitment to clinical trials for cancer in childhood
Lancet Oncol
(2008) - et al.
National cancer clinical trials: children have equal access; adolescents do not
J Adolesc Health
(1997) - et al.
An overview of 48 elderly-specific clinical trials of systemic chemotherapy for advanced non-small cell lung cancer
Lung Cancer
(2004) - et al.
What determines the outcomes for adolescents and young adults with acute lymphoblastic leukemia treated on cooperative group protocols? A comparison of Children's Cancer Group and Cancer and Leukemia Group B studies
Blood
(2008) - et al.
Promoting collaboration between adult and paediatric clinical trial groups
Clin Oncol (R Coll Radiol)
(2008) - et al.
Participation of adolescents with cancer in clinical trials
Cancer Treat Rev
(2007) The adolescent and young adult gap in cancer care and outcome
Curr Probl Pediatr Adolesc Health Care
(2005)Adolescents, young adults, and cancer–the international challenge
Cancer
(2011)
GLOBOCAN (2013). 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Lyon: International Agency for Research on Cancer
Guidance on cancer services—improving outcomes in children and young people with cancer
National survival trends of young adults with sarcoma: lack of progress is associated with lack of clinical trial participation
Cancer
Outcomes for children and adolescents with cancer: challenges for the twenty-first century
J Clin Oncol
The distinctive biology of cancer in adolescents and young adults
Nat Rev Cancer
A systematic review of time to diagnosis in children and young adults with cancer
Arch Dis Child
Proceedings of a workshop: bridging the gap in care and addressing participation in clinical trials
Cancer
Lack of participation of older adolescents and young adults with cancer in clinical trials: impact in the USA
Young adults with leukemia in the United States: lack of clinical trial participation and mortality reduction during the last decade
J Clin Oncol
Rates of inclusion of teenagers and young adults in England into National Cancer Research Network clinical trials: report from the National Cancer Research Institute (NCRI) Teenage and Young Adult Clinical Studies Development Group
Br J Cancer
Surveillance and survival among adolescents and young adults with cancer in Ontario, Canada
Int J Cancer
Cancer in adolescents and young adults: treatment and outcome in Victoria
Med J Aust
Psychosocial management of AYA diagnosed with cancer: guidance of health professionals guidelines and guidance developed by Clinical Oncology Society of Australia, 2013
The need for change, why we need a new model of care for adolescents and young adults with cancer. A document for discussion. Improving the management of cancer services conference. Melbourne 2006
A process for change in the care of adolescents and young adults with cancer in Canada. “Moving to Action”: the Second Canadian International Workshop. International Perspectives on AYAO, Part 1
J Adolesc Young Adult Oncol
Closing the gap: research and care imperatives for adolescents and young adults with cancer (NIH publication no. 06-6067). Bethesda: Department of Health and Human Services, National Institutes of Health, National Cancer Institute, and the LIVESTRONG Young Adult Alliance, 2006
Teenage and Young Adult Clinical Studies Group Annual Report. London: National Cancer Research Institute, 2013
Cited by (96)
Cancer burden in adolescents and young adults in Europe
2023, ESMO OpenAccess to Care for Adolescents and Young Adults with Cancer in the United States: State of the Literature
2024, Journal of Clinical OncologyEvidence-based complementary feeding recipe book for Kenyan caregivers: A novel approach
2024, Maternal and Child Nutrition