- Email: [email protected]
Improving Oncology Clinical Trial Participation and Experience
TRECAN 313 No. of Pages 4
Science & Society
Improving Oncology Clinical Trial Participation and Experience Beth Zaharoff1,* and Simona Cipra1
Patient-related barriers to enrollment in oncology clinical trials have also been identified and evaluated [5–7], which are of concern to TESARO, Inc. as a global, oncology-focused biopharmaceutical company currently conducting clinical trials across its portfolio of pipeline candidates in various cancer types, including ovarian, breast, endometrial, and lung cancers. We aim to design clinical trials that are respectful of the personal needs of patients while maintaining scientific rigor. To this end, we were particularly interested in identifying issues experienced by patients who participated in clinical trials for breast or ovarian cancer and relating them to the well-established recruitment barriers encountered by cancer patients generally.
Cancer patients are underrepresented in clinical trial populations because of protocol-, physician-, and patient-related barriers. We engaged focus groups of patients who had participated in breast and ovarian cancer trials to identify concerns regarding their experiences. The lessons learnt are applicable to improving patient experience Over a 7-month period, we recruited 21 during future trials. prior trial participants with a history of The overarching goal of oncology clinical trials is to improve the health and quality of life of cancer patients. Randomized, controlled clinical trials provide the strongest evidence about new versus established treatments for informed health-care decision making; however, the need to isolate treatment effects by controlling for bias and minimizing variation can affect the generalizability of the results. Generalizability is optimized when patient enrollment rates are high and the recruited population under study reflects the broad spectrum of patients encountered in the clinical practice setting. Yet fewer than 5% of patients with cancer participate in clinical trials [1], with several demographic groups underrepresented [2,3] despite initiatives by federal agencies in the 1980s and 1990s to increase their participation [2]. The demographic imbalance is exacerbated by selection bias on the part of the physician [4] and protocolrelated rigorous selection criteria that often disqualify the elderly and those with preexisting conditions [5,6].
breast or ovarian cancer through partnerships with the support and advocacy organizations Cancer Support Communityi, SHAREii, FORCEiii, and the National Ovarian Cancer Coalitioniv. Inclusion was not limited by participants’ stage of disease or the phase of the clinical trial in which they had participated. Each support and advocacy organization was asked to present the concept of a focus group to their constituents, ascertain interest, and distribute invitations to attend a meeting to recall their clinical trial perceptions and experiences (Figure 1). Focus group meetings were conducted at four geographic locations (California, Michigan, Missouri, and New York) and lasted approximately 2 h. The moderator asked 13 closed- and open-ended questions, providing any necessary clarification and attempting to elicit responses from all participants. Participants agreed in writing to take part and were offered an American Express gift card as a token of appreciation for their time. No identifying information was recorded for any participant, including in the transcript.
The mean age of the 21 participants was 57 years, ranging from 35 to 73 years. A recent cancer diagnosis was breast cancer in 14 women and ovarian cancer in seven women. Participants had enrolled in a clinical trial between 1998 and 2015, with 12 participants having participated in an oncology clinical trial within the past 6 years. Most findings from our focus groups were consistent with those reported in the published literature regarding reasons for and barriers to participating in oncology clinical trials (Table 1). In agreement with previous observations by patients participating in Phase I, II, or III oncology clinical trials [8,9], the motivation to participate in breast and ovarian clinical trials was for altruistic reasons, the hope of finding better treatments or a cure, and the reassurance of careful disease monitoring. As 18 of the 21 participants reported that their oncologist or surgeon informed them of their clinical trial eligibility, lack of clinical trial awareness was not considered as a barrier to enrollment in this sample. Conversely, published reports indicate that only up to 50% of women with breast cancer who could participate in a clinical trial are asked [10,11]. Nevertheless, what constituted the right time to consider clinical trial participation was cited as a concern in the focus groups. Participants indicated a preference for clinical trial notifications by their healthcare provider (or through advocacy groups and clinical trial databases such as ClinicalTrials.govv) rather than by a sponsor on social media due to concerns that the information may be perceived as business focused rather than patient/health focused. Despite generally positive experiences on their clinical trials, barriers that could prevent participation and, more commonly, jeopardize enrollment were identified as key negative drivers. One participant noted
Trends in Cancer, Month Year, Vol. xx, No. yy
1
TRECAN 313 No. of Pages 4
Cancer support community, SHARE, FORCE, and the naonal ovarian cancer coalion Recruitment Prior trial parcipants with a history of breast or ovarian cancer
Quesons on recruitment (qualitave responses and incidence data)
(1) How did you find out about the trial that you parcipated in? (2) Did your doctor bring the study to your aenon? (3) Are there beer methods for recruing paents?
Specific quesons on parcipaon (qualitave responses)
(4) Why did you choose to parcipate? (5) What was the best thing about parcipang? (6) What was the worst thing about parcipang? (7) What did you know at the end of the trial that you wish you would have known at the beginning?
Specific quesons on parcipaon experiences and seng expectaons (incidence data)
(8) Did you feel that your parcipaon in the trial was appreciated? (9) Did you hear anything more about the trial aer your parcipaon in it ended? (10) Would more frequent communicaon have been helpful? (11) Would you parcipate in another trial? (12) Would you recommend parcipang in an oncology clinical trial to somebody else?
Specific queson on recommendaons for improving the experience (qualitave responses)
(13) How could pharmaceucal companies make the experience beer?
Exit forum
Figure 1. Structure of the Recruitment and Questionnaire Process.
alleviate concerns, yet focus group participants (and physicians in general) [14] found the process legally complex, lengthy, and premature in relation to treatment initiation. We recommend that informed consent forms should be reviewed for ease of understanding by someone who is not responsible for writing any part of the form and administered by someone who is knowledgeable about the study. Recruiting physicians are in the ideal position to stress to patients (and their care partners) at the time of informed consent that they will receive access to the most current cancer care, be treated Fortunately, many barriers to oncology and carefully monitored by experts, and clinical trial entry are surmountable by be helping other patients with cancer. improving their design via better support for recruiting physicians and consider- Potential trial participants often face a ation of the participant’s lifestyle during dilemma when deciding whether to enroll the screening, treatment, and follow-up in a trial. Some are apprehensive about phases. The time of informed consent being enrolled in the control arm instead represents the best opportunity to of receiving the potentially superior that recruitment into clinical trials in her geographic region was limited to teaching hospitals, demonstrating again that the center the patient attends can be a barrier to the opportunity to enroll [12]. As observed in cancer trials, including those of breast cancer [6,7,10,13], fear of adverse events, assignment to the placebo or control group, lack of appreciation from clinical trial staff, limited communication about trial status, capacity to assimilate information regarding benefits and risks, and inconvenience were perceived as the main barriers to patient enrollment.
2
Trends in Cancer, Month Year, Vol. xx, No. yy
treatment and others are apprehensive about receiving an unapproved, experimental medication [14,15]. Unbeknown to many is the role of the data and safety monitoring board whose charge is to review the progress of the study to assess whether patients are safe, whether the data are complete, and whether the treatment has an acceptable risk-to-benefit profile. Responses to focus group questions described a lack of appreciation for their clinical trial participation, with expressions of gratitude, engagement with study staff, familiarity with the study site and equipment, and transparency as to the status of the study cited as areas needing improvement. Clearly, patients need to feel more at ease with the entire clinical trial process and have their expectations better managed, especially given the inevitable lack of empowerment that they are likely to encounter during treatment while
TRECAN 313 No. of Pages 4
Table 1. Relevant Findings and Testimonials Emanating from the Focus Groups A lack of understanding that not all doctors offer all clinical trials
& ‘Why doesn’t my oncologist have the trial that I’m interested in?’ The assumption that clinical trials are appropriate only for those who have no other options available
& ‘Are clinical trials only right for people who have no other treatment options available to them?’ The informed consent process is complex
& ‘Consent forms are written for the lawyers’ & ‘It needs to be put in terms a layperson can understand’ & ‘Why are informed consent forms so long?’ & ‘It is important that the person administering informed consent knows the study well’ & ‘It takes too long to qualify’ & ‘Why is there sometimes a long wait between the time I sign the informed consent form and when I can start the clinical trial?’ The clinical trial process is onerous
& ‘It is hard to juggle a work schedule with the study visit schedule’ Hesitance to participate in a clinical trial because of the fear of receiving placebo
& ‘It was a double blind, so I could have gotten a placebo’ Limited expression of appreciation from the clinical trial staff for participating
& ‘I don’t know what would show it but nobody said thank you’ Limited communication about the status of the trial and end-of-study follow up
& ‘There’s been no communicated feedback based on ongoing studies and studies that aren’t successful’ & ‘How can I find out the results of the clinical trial that I participated in?’ The limitation of patients to assimilate all the information that needed to be communicated about the clinical trial benefits and risks
& ‘Fear of not knowing what would happen’ & ‘Being familiar with the equipment and the exam room really helped allay the anxiety’
following the study protocol. Addressing patient depersonalization and a perceived lack of transparency may be achieved, in part, by supplying patients with a singlepage description of the study in lay terminology, a thank-you letter at their first and last study visits, a list of what to expect at each study visit, a cell-phone application documenting reminders, and surveys throughout the study asking about their experience. Patients have a legitimate interest in ongoing clinical trials and want access to the results of completed clinical trials [13]. Therefore, within legal and ethical bounds, greater public disclosure of information on clinical study protocols and results is needed.
personal schedules was difficult. Instituting a range of measures that improve clinical trial logistics will help to alleviate this burden, such as prioritizing convenient visit times and reimbursing patients for expenses related to their participation.
patients are well positioned to inform investigators about their concerns so that more patients may be willing to participate in the future, thereby improving the generalizability of oncology clinical trials. Acknowledgments
Although our findings were neither obtained in a controlled environment nor quantified, they corroborate extensively results from systematic reviews of the literature [6,7].
In conclusion, our anecdotal findings reconfirm that patients have negative encounters related to clinical trial sites, processes, social interactions, and data dissemination. Greater connectivity is The focus groups reported that balancing required among all stakeholders to win study visit schedules around work and the support of patients. Recruited
The authors acknowledge the advocacy organizations that assisted with finding focus group participants: the Cancer Support Community, SHARE, FORCE, and the National Ovarian Cancer Coalition. These advocacy groups had the opportunity to review the manuscript prior to publication. Medical writing and editorial support, funded by TESARO, Inc. (Waltham, MA) and coordinated by Teodor G. Paunescu, PhD of TESARO, Inc., was provided by Malcolm Darkes, PhD and Paula Stuckart of Ashfield Healthcare Communications and Richard Perry, PharmD. Many thanks go to Aubri Lang, Megan Duncan, and Kristen Perkins who helped to facilitate the focus groups and noted key points throughout.
Trends in Cancer, Month Year, Vol. xx, No. yy
3
TRECAN 313 No. of Pages 4
Resources i
www.cancersupportcommunity.org/
ii
www.sharecancersupport.org/
iii
www.facingourrisk.org/
iv v
http://ovarian.org/
https://clinicaltrials.gov/
1
TESARO, Inc., Waltham, MA, USA
*Correspondence: [email protected] (B. Zaharoff). https://doi.org/10.1016/j.trecan.2018.10.007 References 1. Avis, N.E. et al. (2006) Factors associated with participation in breast cancer treatment clinical trials. J. Clin. Oncol. 24, 1860–1867 2. Hutchins, L.F. et al. (1999) Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N. Engl. J. Med. 341, 2061–2067
4
Trends in Cancer, Month Year, Vol. xx, No. yy
3. Murthy, V.H. et al. (2004) Participation in cancer clinical trials: race-, sex-, and age-based disparities. JAMA 291, 2720–2726 4. Antman, K. et al. (1985) Selection bias in clinical trials. J. Clin. Oncol. 3, 1142–1147 5. Townsley, C.A. et al. (2005) Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials. J. Clin. Oncol. 23, 3112–3124 6. Mills, E.J. et al. (2006) Barriers to participation in clinical trials of cancer: a meta-analysis and systematic review of patient-reported factors. Lancet Oncol. 7, 141–148 7. Ford, J.G. et al. (2008) Barriers to recruiting underrepresented populations to cancer clinical trials: a systematic review. Cancer 112, 228–242 8. Godskesen, T. et al. (2015) Hope for a cure and altruism are the main motives behind participation in Phase 3 clinical cancer trials. Eur. J. Cancer Care (Engl.) 24, 133–141 9. Truong, T.H. et al. (2011) Altruism among participants in cancer clinical trials. Clin. Trials 8, 616–623
10. Morris, A.F. et al. (2014) Perceptions about cancer clinical trials among metastatic breast cancer patients: findings from a patient powered registry. Poster presented at the San Antonio Breast Cancer Symposium, San Antonio, Texas, December 9–13, 2014 11. Siminoff, L.A. et al. (2000) Factors that predict the referral of breast cancer patients onto clinical trials by their surgeons and medical oncologists. J. Clin. Oncol. 18, 1203–1211 12. Carey, M. et al. (2017) Access to clinical trials among oncology patients: results of a cross sectional survey. BMC Cancer 1, 653 13. Hudson, K.L. and Collins, F.S. (2015) Sharing and reporting the results of clinical trials. JAMA 313, 355–356 14. Somkin, C.P. et al. (2013) Effect of medical oncologists’ attitudes on accrual to clinical trials in a community setting. J. Oncol. Pract. 9, e275–e283 15. Ferhanoglu, B. et al. (2018) Venetoclax–rituximab in chronic lymphocytic leukemia. N. Engl. J. Med. 378, 2141–2142
Science & Society
Improving Oncology Clinical Trial Participation and Experience Beth Zaharoff1,* and Simona Cipra1
Patient-related barriers to enrollment in oncology clinical trials have also been identified and evaluated [5–7], which are of concern to TESARO, Inc. as a global, oncology-focused biopharmaceutical company currently conducting clinical trials across its portfolio of pipeline candidates in various cancer types, including ovarian, breast, endometrial, and lung cancers. We aim to design clinical trials that are respectful of the personal needs of patients while maintaining scientific rigor. To this end, we were particularly interested in identifying issues experienced by patients who participated in clinical trials for breast or ovarian cancer and relating them to the well-established recruitment barriers encountered by cancer patients generally.
Cancer patients are underrepresented in clinical trial populations because of protocol-, physician-, and patient-related barriers. We engaged focus groups of patients who had participated in breast and ovarian cancer trials to identify concerns regarding their experiences. The lessons learnt are applicable to improving patient experience Over a 7-month period, we recruited 21 during future trials. prior trial participants with a history of The overarching goal of oncology clinical trials is to improve the health and quality of life of cancer patients. Randomized, controlled clinical trials provide the strongest evidence about new versus established treatments for informed health-care decision making; however, the need to isolate treatment effects by controlling for bias and minimizing variation can affect the generalizability of the results. Generalizability is optimized when patient enrollment rates are high and the recruited population under study reflects the broad spectrum of patients encountered in the clinical practice setting. Yet fewer than 5% of patients with cancer participate in clinical trials [1], with several demographic groups underrepresented [2,3] despite initiatives by federal agencies in the 1980s and 1990s to increase their participation [2]. The demographic imbalance is exacerbated by selection bias on the part of the physician [4] and protocolrelated rigorous selection criteria that often disqualify the elderly and those with preexisting conditions [5,6].
breast or ovarian cancer through partnerships with the support and advocacy organizations Cancer Support Communityi, SHAREii, FORCEiii, and the National Ovarian Cancer Coalitioniv. Inclusion was not limited by participants’ stage of disease or the phase of the clinical trial in which they had participated. Each support and advocacy organization was asked to present the concept of a focus group to their constituents, ascertain interest, and distribute invitations to attend a meeting to recall their clinical trial perceptions and experiences (Figure 1). Focus group meetings were conducted at four geographic locations (California, Michigan, Missouri, and New York) and lasted approximately 2 h. The moderator asked 13 closed- and open-ended questions, providing any necessary clarification and attempting to elicit responses from all participants. Participants agreed in writing to take part and were offered an American Express gift card as a token of appreciation for their time. No identifying information was recorded for any participant, including in the transcript.
The mean age of the 21 participants was 57 years, ranging from 35 to 73 years. A recent cancer diagnosis was breast cancer in 14 women and ovarian cancer in seven women. Participants had enrolled in a clinical trial between 1998 and 2015, with 12 participants having participated in an oncology clinical trial within the past 6 years. Most findings from our focus groups were consistent with those reported in the published literature regarding reasons for and barriers to participating in oncology clinical trials (Table 1). In agreement with previous observations by patients participating in Phase I, II, or III oncology clinical trials [8,9], the motivation to participate in breast and ovarian clinical trials was for altruistic reasons, the hope of finding better treatments or a cure, and the reassurance of careful disease monitoring. As 18 of the 21 participants reported that their oncologist or surgeon informed them of their clinical trial eligibility, lack of clinical trial awareness was not considered as a barrier to enrollment in this sample. Conversely, published reports indicate that only up to 50% of women with breast cancer who could participate in a clinical trial are asked [10,11]. Nevertheless, what constituted the right time to consider clinical trial participation was cited as a concern in the focus groups. Participants indicated a preference for clinical trial notifications by their healthcare provider (or through advocacy groups and clinical trial databases such as ClinicalTrials.govv) rather than by a sponsor on social media due to concerns that the information may be perceived as business focused rather than patient/health focused. Despite generally positive experiences on their clinical trials, barriers that could prevent participation and, more commonly, jeopardize enrollment were identified as key negative drivers. One participant noted
Trends in Cancer, Month Year, Vol. xx, No. yy
1
TRECAN 313 No. of Pages 4
Cancer support community, SHARE, FORCE, and the naonal ovarian cancer coalion Recruitment Prior trial parcipants with a history of breast or ovarian cancer
Quesons on recruitment (qualitave responses and incidence data)
(1) How did you find out about the trial that you parcipated in? (2) Did your doctor bring the study to your aenon? (3) Are there beer methods for recruing paents?
Specific quesons on parcipaon (qualitave responses)
(4) Why did you choose to parcipate? (5) What was the best thing about parcipang? (6) What was the worst thing about parcipang? (7) What did you know at the end of the trial that you wish you would have known at the beginning?
Specific quesons on parcipaon experiences and seng expectaons (incidence data)
(8) Did you feel that your parcipaon in the trial was appreciated? (9) Did you hear anything more about the trial aer your parcipaon in it ended? (10) Would more frequent communicaon have been helpful? (11) Would you parcipate in another trial? (12) Would you recommend parcipang in an oncology clinical trial to somebody else?
Specific queson on recommendaons for improving the experience (qualitave responses)
(13) How could pharmaceucal companies make the experience beer?
Exit forum
Figure 1. Structure of the Recruitment and Questionnaire Process.
alleviate concerns, yet focus group participants (and physicians in general) [14] found the process legally complex, lengthy, and premature in relation to treatment initiation. We recommend that informed consent forms should be reviewed for ease of understanding by someone who is not responsible for writing any part of the form and administered by someone who is knowledgeable about the study. Recruiting physicians are in the ideal position to stress to patients (and their care partners) at the time of informed consent that they will receive access to the most current cancer care, be treated Fortunately, many barriers to oncology and carefully monitored by experts, and clinical trial entry are surmountable by be helping other patients with cancer. improving their design via better support for recruiting physicians and consider- Potential trial participants often face a ation of the participant’s lifestyle during dilemma when deciding whether to enroll the screening, treatment, and follow-up in a trial. Some are apprehensive about phases. The time of informed consent being enrolled in the control arm instead represents the best opportunity to of receiving the potentially superior that recruitment into clinical trials in her geographic region was limited to teaching hospitals, demonstrating again that the center the patient attends can be a barrier to the opportunity to enroll [12]. As observed in cancer trials, including those of breast cancer [6,7,10,13], fear of adverse events, assignment to the placebo or control group, lack of appreciation from clinical trial staff, limited communication about trial status, capacity to assimilate information regarding benefits and risks, and inconvenience were perceived as the main barriers to patient enrollment.
2
Trends in Cancer, Month Year, Vol. xx, No. yy
treatment and others are apprehensive about receiving an unapproved, experimental medication [14,15]. Unbeknown to many is the role of the data and safety monitoring board whose charge is to review the progress of the study to assess whether patients are safe, whether the data are complete, and whether the treatment has an acceptable risk-to-benefit profile. Responses to focus group questions described a lack of appreciation for their clinical trial participation, with expressions of gratitude, engagement with study staff, familiarity with the study site and equipment, and transparency as to the status of the study cited as areas needing improvement. Clearly, patients need to feel more at ease with the entire clinical trial process and have their expectations better managed, especially given the inevitable lack of empowerment that they are likely to encounter during treatment while
TRECAN 313 No. of Pages 4
Table 1. Relevant Findings and Testimonials Emanating from the Focus Groups A lack of understanding that not all doctors offer all clinical trials
& ‘Why doesn’t my oncologist have the trial that I’m interested in?’ The assumption that clinical trials are appropriate only for those who have no other options available
& ‘Are clinical trials only right for people who have no other treatment options available to them?’ The informed consent process is complex
& ‘Consent forms are written for the lawyers’ & ‘It needs to be put in terms a layperson can understand’ & ‘Why are informed consent forms so long?’ & ‘It is important that the person administering informed consent knows the study well’ & ‘It takes too long to qualify’ & ‘Why is there sometimes a long wait between the time I sign the informed consent form and when I can start the clinical trial?’ The clinical trial process is onerous
& ‘It is hard to juggle a work schedule with the study visit schedule’ Hesitance to participate in a clinical trial because of the fear of receiving placebo
& ‘It was a double blind, so I could have gotten a placebo’ Limited expression of appreciation from the clinical trial staff for participating
& ‘I don’t know what would show it but nobody said thank you’ Limited communication about the status of the trial and end-of-study follow up
& ‘There’s been no communicated feedback based on ongoing studies and studies that aren’t successful’ & ‘How can I find out the results of the clinical trial that I participated in?’ The limitation of patients to assimilate all the information that needed to be communicated about the clinical trial benefits and risks
& ‘Fear of not knowing what would happen’ & ‘Being familiar with the equipment and the exam room really helped allay the anxiety’
following the study protocol. Addressing patient depersonalization and a perceived lack of transparency may be achieved, in part, by supplying patients with a singlepage description of the study in lay terminology, a thank-you letter at their first and last study visits, a list of what to expect at each study visit, a cell-phone application documenting reminders, and surveys throughout the study asking about their experience. Patients have a legitimate interest in ongoing clinical trials and want access to the results of completed clinical trials [13]. Therefore, within legal and ethical bounds, greater public disclosure of information on clinical study protocols and results is needed.
personal schedules was difficult. Instituting a range of measures that improve clinical trial logistics will help to alleviate this burden, such as prioritizing convenient visit times and reimbursing patients for expenses related to their participation.
patients are well positioned to inform investigators about their concerns so that more patients may be willing to participate in the future, thereby improving the generalizability of oncology clinical trials. Acknowledgments
Although our findings were neither obtained in a controlled environment nor quantified, they corroborate extensively results from systematic reviews of the literature [6,7].
In conclusion, our anecdotal findings reconfirm that patients have negative encounters related to clinical trial sites, processes, social interactions, and data dissemination. Greater connectivity is The focus groups reported that balancing required among all stakeholders to win study visit schedules around work and the support of patients. Recruited
The authors acknowledge the advocacy organizations that assisted with finding focus group participants: the Cancer Support Community, SHARE, FORCE, and the National Ovarian Cancer Coalition. These advocacy groups had the opportunity to review the manuscript prior to publication. Medical writing and editorial support, funded by TESARO, Inc. (Waltham, MA) and coordinated by Teodor G. Paunescu, PhD of TESARO, Inc., was provided by Malcolm Darkes, PhD and Paula Stuckart of Ashfield Healthcare Communications and Richard Perry, PharmD. Many thanks go to Aubri Lang, Megan Duncan, and Kristen Perkins who helped to facilitate the focus groups and noted key points throughout.
Trends in Cancer, Month Year, Vol. xx, No. yy
3
TRECAN 313 No. of Pages 4
Resources i
www.cancersupportcommunity.org/
ii
www.sharecancersupport.org/
iii
www.facingourrisk.org/
iv v
http://ovarian.org/
https://clinicaltrials.gov/
1
TESARO, Inc., Waltham, MA, USA
*Correspondence: [email protected] (B. Zaharoff). https://doi.org/10.1016/j.trecan.2018.10.007 References 1. Avis, N.E. et al. (2006) Factors associated with participation in breast cancer treatment clinical trials. J. Clin. Oncol. 24, 1860–1867 2. Hutchins, L.F. et al. (1999) Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N. Engl. J. Med. 341, 2061–2067
4
Trends in Cancer, Month Year, Vol. xx, No. yy
3. Murthy, V.H. et al. (2004) Participation in cancer clinical trials: race-, sex-, and age-based disparities. JAMA 291, 2720–2726 4. Antman, K. et al. (1985) Selection bias in clinical trials. J. Clin. Oncol. 3, 1142–1147 5. Townsley, C.A. et al. (2005) Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials. J. Clin. Oncol. 23, 3112–3124 6. Mills, E.J. et al. (2006) Barriers to participation in clinical trials of cancer: a meta-analysis and systematic review of patient-reported factors. Lancet Oncol. 7, 141–148 7. Ford, J.G. et al. (2008) Barriers to recruiting underrepresented populations to cancer clinical trials: a systematic review. Cancer 112, 228–242 8. Godskesen, T. et al. (2015) Hope for a cure and altruism are the main motives behind participation in Phase 3 clinical cancer trials. Eur. J. Cancer Care (Engl.) 24, 133–141 9. Truong, T.H. et al. (2011) Altruism among participants in cancer clinical trials. Clin. Trials 8, 616–623
10. Morris, A.F. et al. (2014) Perceptions about cancer clinical trials among metastatic breast cancer patients: findings from a patient powered registry. Poster presented at the San Antonio Breast Cancer Symposium, San Antonio, Texas, December 9–13, 2014 11. Siminoff, L.A. et al. (2000) Factors that predict the referral of breast cancer patients onto clinical trials by their surgeons and medical oncologists. J. Clin. Oncol. 18, 1203–1211 12. Carey, M. et al. (2017) Access to clinical trials among oncology patients: results of a cross sectional survey. BMC Cancer 1, 653 13. Hudson, K.L. and Collins, F.S. (2015) Sharing and reporting the results of clinical trials. JAMA 313, 355–356 14. Somkin, C.P. et al. (2013) Effect of medical oncologists’ attitudes on accrual to clinical trials in a community setting. J. Oncol. Pract. 9, e275–e283 15. Ferhanoglu, B. et al. (2018) Venetoclax–rituximab in chronic lymphocytic leukemia. N. Engl. J. Med. 378, 2141–2142