Available, accessible, aware, appropriate, and acceptable: a strategy to improve participation of teenagers and young adults in cancer trials

Summary

Under-representation of teenagers and young adults in clinical trials for cancer is acknowledged internationally and might account for the lower survival gains noted for this group. Little research has focused on strategies to increase participation of teenagers and young adults in clinical trials. We applied a conceptual framework for barriers to recruitment of under-represented populations to data for cancer clinical trials in teenagers and young adults. We did a systematic analysis of data for clinical trial enrolment in Great Britain over 6 years (2005–10), and reviewed the published work for the origins and scientific rationale of age eligibility criteria in clinical trials for cancer. Our Review revealed little scientific evidence for use of age eligibility criteria in cancer clinical trials. Participation in cancer trials fell as age increased. Between 2005 and 2010, participation rates increased for children and young people aged 0–24 years. The highest increase in participation was for teenagers aged 15–19 years, with smaller improvements in rates for 20–24 year olds. Improvements were related to five key criteria, the five As: available, accessible, aware, appropriate, and acceptable. In studies for which age eligibility criteria were appropriate for inclusion of teenagers or young adults or amended during the study period, participation rates for 15–19 year olds were similar to those for 10–14 year olds. We propose a conceptual model for a strategic approach to improve recruitment of teenagers and younger adults to clinical trials for cancer, with use of the five As, which is applicable worldwide for investigators, regulatory authorities, representatives in industry, policy makers, funders, and health-care professionals.

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.