Review
Available, accessible, aware, appropriate, and acceptable: a strategy to improve participation of teenagers and young adults in cancer trials Lorna A Fern, Jennifer A Lewandowski, Katy M Coxon, Jeremy Whelan, for the National Cancer Research Institute Teenage and Young Adult Clinical Studies Group, UK
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.4–6 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 www.thelancet.com/oncology Vol 15 July 2014
treatment protocols, and poorer rates of participation in clinical trials.5,7–9 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.5,10–15 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.2,16–19 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,
Lancet Oncol 2014; 15: e341–50 See Online for author interview with Jeremy Whelan Department of Oncology, University College London Hospitals Foundation NHS Trust, London, UK (L A Fern PhD, Prof J Whelan MD); National Cancer Research Institute Teenage and Young Adult Clinical Studies Group, London, UK (L A Fern, Prof J Whelan); and National Cancer Research Institute, London, UK (J A Lewandowski MS, K M Coxon PhD) Correspondence to: Prof Jeremy Whelan, Department of Oncology, University College London Hospitals, London NW1 2PG, UK [email protected]
e341
Review
For the Cochrane Library see http://www.cochrane.org
See Online for appendix
For the website of The Office for National Statistics for cancer incidence rates in England see http://www.ons.gov.uk/ons/rel/ vsobl/cancer-statisticsregistrations--england--seriesmbl-/index.hml For the website of the Welsh Cancer Intelligence and Surveillance Unit for cancer incidence rates in Wales see http://www.wcisu.wales.nhs.uk/ cancer-statistics For the website of the Information Services Division for cancer incidence rates in Scotland see http://www. isdscotland.org/Health-Topics/ Cancer/Cancer-Statistics/
e342
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, underrepresented groups in clinical trials for cancer are well described and include ethnic minority populations, people of low socioeconomic status, elderly patients, and young people.5,10,12,14,23–28 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.
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 older adults in Great Britain using previously described methodology12 expanded to include soft-tissue sarcoma and wider geographical coverage. We obtained data for cancer incidence from cancer registries in England, Scotland, and Wales. The Office for National Statistics provided data for England; series MB1, numbers 36–41, correspond to incidence in 2005–10. We extracted incidence data for Wales from the following reports: SA06/02 (2005), SA08/01 (2006), SA09/01 (2007), SA10/01 (2008), SA11/01 (2009), and SA12/01 (2010), released by the Welsh Cancer Intelligence and Surveillance Unit. We used Cancer Incidence in Scotland, 2010, issued by the Information Services Division to obtain data for Scotland. Data were extracted from accompanying data tables, which contained cancer incidence data from 1986 to 2010. We expressed concurrent accrual and participation rates as the proportion of patients entered into trials for the selected
cancer types compared with the number of new cases of that cancer reported that year. We analysed overall participation rates for 2005–10, followed by trends in participation between 2005–07 and 2008–10. We applied descriptive statistics, judging this strategy to be appropriate for an observational dataset in which the sample size or the number of incidence cases could not be controlled.12 To establish the origins and scientific rationale for age eligibility criteria, we broadly followed a PRISMA approach, searching PubMed and relevant databases for articles published in English 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”. We supplemented our search strategy with an author search of experts known to have an interest in our questions, examination of the reference lists in certain articles, and an examination of our files. We also searched the Cochrane Library for systematic reviews on the subject. Our decision to include or reject articles was based on relevance and quality.
Findings 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 562 (14%) of 4011 patients aged 20–24 years. In the 6 years, participation rates improved overall for children and young people aged up to 24 years (figure 1A). The largest increase was a 13% increase in trial participation for teenagers aged 15–19 years from 2005–10 (from 116 [24%] of 481 individuals to 184 [37%] of 492). We noted smaller improvements (from 88 [14%] of 653 individuals to 129 [18%] of 713; change of 5%) for young people aged 20–24 years over the same time period (figure 1B, table 1, appendix pp 7–9). For patients aged 15–19 years, the largest improvements in participation was for trials of Hodgkin’s lymphoma (participation increased by 29% between 2005–07 and 2008–10), brain and CNS tumours (10%), and bone sarcomas (9%; table 2). In patients aged 20–24 years, improvements were largest for trials of bone sarcomas (participation increased by 21% between 2005–07 and 2008–10) and Hodgkin’s lymphoma (6%; table 2 and appendix p 9). In 2010, about half (55%) of all children and young teenagers aged 5–14 years diagnosed with cancer were enrolled into trials, compared with a quarter www.thelancet.com/oncology Vol 15 July 2014
A
B
70
70
60
60
50
50 Patients recruited (%)
Patients recruited (%)
Review
40
30
40
30
20
20
10
10
0
0–4
2005 2006 2007 2008 2009 2010
0
5–9 10–14 15–19 20–24 25–29 30–34 35–39 40–44 45–49 50–54 55–59
0–14
15–19
Age at accrual (years)
20–24
Age at accrual (years)
C
D
LGG2, 18 years, December, 2007–ongoing 30
EORTC 22042-EORTC 26042, >18 years, November, 2008–June, 2013 IMA 950, >18 years, September, 2010–ongoing
20
20 10 10 0
0–4
5–9
10–14 15–19 20–24 25–29 30–34 35–39 40–44 45–49
Age at accrual (years)
0
0–4
5–9
10–14
15–19 20–24 29–29 30–34 35–39 40–44 45–49 50–54 55–59 Age at accrual (years)
Figure 1: Participation in trials (A) Proportion of children, teenagers and young adults, and older adults entered into selected cancer trials during our study period. Dotted box represents teenage and young adult age groups. (B) Changes in proportion of patients entered in selected cancer trials per year. (C) Proportion of patients entered into trials for bone sarcoma. Lines depict age ranges of trials included in our analysis; corresponding age eligibility criteria and opening and closing dates are given. (D) Patients entered into trials for tumours of the brain and CNS in 2005–07 and 2008–10. Lines depict age ranges of trials included in our analysis; corresponding age eligibility criteria and opening and closing dates are given. Data are for England, Scotland, and Wales, from April 1, 2005, and March 31, 2011.
(26%) of patients aged 15–24 years, despite cancer incidence in the latter patient group being more than double the incidence reported in 5–14 year olds in 2010 (584 cases in children aged 5–14 years vs 1205 cases in children aged 20–24 years in the cancer types that we analysed, appendix p 7. www.thelancet.com/oncology Vol 15 July 2014
Only six of 49 studies of cancers common in teenagers and young adults had age eligibility criteria that could be deemed appropriate for the biological age range of the diseases, and span the complete age cohort of teenage and young adult cancers (rational eligibility criteria): Euro-Ewing 99, and EURAMOS-1, both recruiting e343
Review
0–14 years
15–19 years
20–24 years
Number of patients Number of patients Accrual diagnosed with cancer entered into trials (%)
Number of patients Number of patients Accrual diagnosed with cancer entered into trials (%)
Number of patients diagnosed with cancer
Number of patients entered into trials
Accrual (%)
2005
1005
518
52%
481
116
24%
653
88
14%
2006
1028
527
51%
456
119
26%
633
81
13%
2007
978
533
55%
465
128
28%
659
63
10%
2008
1020
612
60%
457
133
29%
668
83
12%
2009
1069
532
50%
509
170
33%
685
118
17%
2010
1025
594
58%
492
184
37%
713
129
18%
Overall 2005–10
6125
3316
54%
2860
850
30%
4011
562
14%
Change from 2005 to 2010 (%)
7%
13%
5%
Numbers given for England, Scotland, and Wales, from March 31, 2005, to April 1, 2010.
Table 1: Trends in participation in clinical trials for children, teenagers, and young adults between 2005 and 2010
0–14 years
15–19 years
20–24 years
Accrual Number of patients Number of patients entered (%) diagnosed with into trials cancer
Accrual Number of patients Number of patients entered (%) diagnosed with into trials cancer
Accrual Number of patients Number of patients entered (%) diagnosed with into trials cancer
Solid cancers Bone sarcoma 2005–10
414
278
67%
311
200
64%
218
63
2005–07
181
117
65%
157
94
60%
109
20
18%
2008–10
233
161
69%
154
106
69%
109
43
39%
Change from 2005–07 to 2008–10 (%)
5%
9%
29%
21%
Brain and CNS 2005–10
1732
486
28%
391
60
15%
463
Available, accessible, aware, appropriate, and acceptable: a strategy to improve participation of teenagers and young adults in cancer trials Lorna A Fern, Jennifer A Lewandowski, Katy M Coxon, Jeremy Whelan, for the National Cancer Research Institute Teenage and Young Adult Clinical Studies Group, UK
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.4–6 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 www.thelancet.com/oncology Vol 15 July 2014
treatment protocols, and poorer rates of participation in clinical trials.5,7–9 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.5,10–15 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.2,16–19 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,
Lancet Oncol 2014; 15: e341–50 See Online for author interview with Jeremy Whelan Department of Oncology, University College London Hospitals Foundation NHS Trust, London, UK (L A Fern PhD, Prof J Whelan MD); National Cancer Research Institute Teenage and Young Adult Clinical Studies Group, London, UK (L A Fern, Prof J Whelan); and National Cancer Research Institute, London, UK (J A Lewandowski MS, K M Coxon PhD) Correspondence to: Prof Jeremy Whelan, Department of Oncology, University College London Hospitals, London NW1 2PG, UK [email protected]
e341
Review
For the Cochrane Library see http://www.cochrane.org
See Online for appendix
For the website of The Office for National Statistics for cancer incidence rates in England see http://www.ons.gov.uk/ons/rel/ vsobl/cancer-statisticsregistrations--england--seriesmbl-/index.hml For the website of the Welsh Cancer Intelligence and Surveillance Unit for cancer incidence rates in Wales see http://www.wcisu.wales.nhs.uk/ cancer-statistics For the website of the Information Services Division for cancer incidence rates in Scotland see http://www. isdscotland.org/Health-Topics/ Cancer/Cancer-Statistics/
e342
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, underrepresented groups in clinical trials for cancer are well described and include ethnic minority populations, people of low socioeconomic status, elderly patients, and young people.5,10,12,14,23–28 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.
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 older adults in Great Britain using previously described methodology12 expanded to include soft-tissue sarcoma and wider geographical coverage. We obtained data for cancer incidence from cancer registries in England, Scotland, and Wales. The Office for National Statistics provided data for England; series MB1, numbers 36–41, correspond to incidence in 2005–10. We extracted incidence data for Wales from the following reports: SA06/02 (2005), SA08/01 (2006), SA09/01 (2007), SA10/01 (2008), SA11/01 (2009), and SA12/01 (2010), released by the Welsh Cancer Intelligence and Surveillance Unit. We used Cancer Incidence in Scotland, 2010, issued by the Information Services Division to obtain data for Scotland. Data were extracted from accompanying data tables, which contained cancer incidence data from 1986 to 2010. We expressed concurrent accrual and participation rates as the proportion of patients entered into trials for the selected
cancer types compared with the number of new cases of that cancer reported that year. We analysed overall participation rates for 2005–10, followed by trends in participation between 2005–07 and 2008–10. We applied descriptive statistics, judging this strategy to be appropriate for an observational dataset in which the sample size or the number of incidence cases could not be controlled.12 To establish the origins and scientific rationale for age eligibility criteria, we broadly followed a PRISMA approach, searching PubMed and relevant databases for articles published in English 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”. We supplemented our search strategy with an author search of experts known to have an interest in our questions, examination of the reference lists in certain articles, and an examination of our files. We also searched the Cochrane Library for systematic reviews on the subject. Our decision to include or reject articles was based on relevance and quality.
Findings 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 562 (14%) of 4011 patients aged 20–24 years. In the 6 years, participation rates improved overall for children and young people aged up to 24 years (figure 1A). The largest increase was a 13% increase in trial participation for teenagers aged 15–19 years from 2005–10 (from 116 [24%] of 481 individuals to 184 [37%] of 492). We noted smaller improvements (from 88 [14%] of 653 individuals to 129 [18%] of 713; change of 5%) for young people aged 20–24 years over the same time period (figure 1B, table 1, appendix pp 7–9). For patients aged 15–19 years, the largest improvements in participation was for trials of Hodgkin’s lymphoma (participation increased by 29% between 2005–07 and 2008–10), brain and CNS tumours (10%), and bone sarcomas (9%; table 2). In patients aged 20–24 years, improvements were largest for trials of bone sarcomas (participation increased by 21% between 2005–07 and 2008–10) and Hodgkin’s lymphoma (6%; table 2 and appendix p 9). In 2010, about half (55%) of all children and young teenagers aged 5–14 years diagnosed with cancer were enrolled into trials, compared with a quarter www.thelancet.com/oncology Vol 15 July 2014
A
B
70
70
60
60
50
50 Patients recruited (%)
Patients recruited (%)
Review
40
30
40
30
20
20
10
10
0
0–4
2005 2006 2007 2008 2009 2010
0
5–9 10–14 15–19 20–24 25–29 30–34 35–39 40–44 45–49 50–54 55–59
0–14
15–19
Age at accrual (years)
20–24
Age at accrual (years)
C
D
LGG2, 18 years, December, 2007–ongoing 30
EORTC 22042-EORTC 26042, >18 years, November, 2008–June, 2013 IMA 950, >18 years, September, 2010–ongoing
20
20 10 10 0
0–4
5–9
10–14 15–19 20–24 25–29 30–34 35–39 40–44 45–49
Age at accrual (years)
0
0–4
5–9
10–14
15–19 20–24 29–29 30–34 35–39 40–44 45–49 50–54 55–59 Age at accrual (years)
Figure 1: Participation in trials (A) Proportion of children, teenagers and young adults, and older adults entered into selected cancer trials during our study period. Dotted box represents teenage and young adult age groups. (B) Changes in proportion of patients entered in selected cancer trials per year. (C) Proportion of patients entered into trials for bone sarcoma. Lines depict age ranges of trials included in our analysis; corresponding age eligibility criteria and opening and closing dates are given. (D) Patients entered into trials for tumours of the brain and CNS in 2005–07 and 2008–10. Lines depict age ranges of trials included in our analysis; corresponding age eligibility criteria and opening and closing dates are given. Data are for England, Scotland, and Wales, from April 1, 2005, and March 31, 2011.
(26%) of patients aged 15–24 years, despite cancer incidence in the latter patient group being more than double the incidence reported in 5–14 year olds in 2010 (584 cases in children aged 5–14 years vs 1205 cases in children aged 20–24 years in the cancer types that we analysed, appendix p 7. www.thelancet.com/oncology Vol 15 July 2014
Only six of 49 studies of cancers common in teenagers and young adults had age eligibility criteria that could be deemed appropriate for the biological age range of the diseases, and span the complete age cohort of teenage and young adult cancers (rational eligibility criteria): Euro-Ewing 99, and EURAMOS-1, both recruiting e343
Review
0–14 years
15–19 years
20–24 years
Number of patients Number of patients Accrual diagnosed with cancer entered into trials (%)
Number of patients Number of patients Accrual diagnosed with cancer entered into trials (%)
Number of patients diagnosed with cancer
Number of patients entered into trials
Accrual (%)
2005
1005
518
52%
481
116
24%
653
88
14%
2006
1028
527
51%
456
119
26%
633
81
13%
2007
978
533
55%
465
128
28%
659
63
10%
2008
1020
612
60%
457
133
29%
668
83
12%
2009
1069
532
50%
509
170
33%
685
118
17%
2010
1025
594
58%
492
184
37%
713
129
18%
Overall 2005–10
6125
3316
54%
2860
850
30%
4011
562
14%
Change from 2005 to 2010 (%)
7%
13%
5%
Numbers given for England, Scotland, and Wales, from March 31, 2005, to April 1, 2010.
Table 1: Trends in participation in clinical trials for children, teenagers, and young adults between 2005 and 2010
0–14 years
15–19 years
20–24 years
Accrual Number of patients Number of patients entered (%) diagnosed with into trials cancer
Accrual Number of patients Number of patients entered (%) diagnosed with into trials cancer
Accrual Number of patients Number of patients entered (%) diagnosed with into trials cancer
Solid cancers Bone sarcoma 2005–10
414
278
67%
311
200
64%
218
63
2005–07
181
117
65%
157
94
60%
109
20
18%
2008–10
233
161
69%
154
106
69%
109
43
39%
Change from 2005–07 to 2008–10 (%)
5%
9%
29%
21%
Brain and CNS 2005–10
1732
486
28%
391
60
15%
463
