Exclusion of people from oncology clinical trials based on functional status

Abstract

Background/Aims:

People with disability have higher rates of cancer, excluding skin cancer, compared with people without disability. Food and Drug Administration draft guidelines from 2024 address use of performance status criteria to determine eligibility for clinical trials, advocating for less restrictive thresholds. We examined the exclusion of people with disability from clinical trials based on performance status and other criteria.

Methods:

We reviewed eligibility criteria in approved interventional Phase III and Phase IV oncology clinical trials listed on ClinicalTrails.gov between 1 January 2019 and 31 December 2023. Functional status thresholds were assessed using the Eastern Cooperative Oncology Group Performance Status Scale and Karnofsky Performance Scale in clinical trial eligibility criteria. Qualitative analysis was used to review eligibility criteria relating to functional impairments or disability.

Results:

Among 96 oncology clinical trials, approximately 40% had restrictive Eastern Cooperative Oncology Group and Karnofsky Performance Scale thresholds, explicitly including only patients with Eastern Cooperative Oncology Group 0 or 1, or equivalent Karnofsky Performance Scale 70 or greater. Only 20% of studies included patients with Eastern Cooperative Oncology Group 2 and Karnofsky Performance Scale 60. Multiple studies contained miscellaneous eligibility criteria that could potentially exclude people with disability. No studies described making accommodations for people with disability to participate in the clinical trial.

Conclusion:

Draft Food and Drug Administration guidelines recommend including patients with Eastern Cooperative Oncology Group scores of 2 and Karnofsky Performance Scale scores of 60 in oncology clinical trials. We found that oncology clinical trials often exclude people with more restrictive performance status scores than the draft Food and Drug Administration guidelines, as well as other criteria that relate to disability. These estimates provide baseline information for assessing how the 2024 Food and Drug Administration guidance, if finalized, might affect the inclusion of people with disability in future trials.

Keywords

Performance status clinical trials disability

Introduction

Approximately one in four (27%) adult Americans report some type of disability.^1,2 Estimates from 2022 suggest that adults with disability have higher cancer rates, excluding skin cancer, compared with nondisabled adults (9.1% vs. 6.1%).³ Pre-existing disability is associated with significantly higher rates of cervical, breast, colorectal, and prostate cancers, and non-Hodgkin lymphoma compared with nondisabled peers.^4,5 Nevertheless, people with disability encounter barriers and delays to cancer diagnosis and treatment^6–8 often caused by diagnostic overshadowing,^9,10 inaccessible medical diagnostic equipment,¹⁰ exclusion from clinical trials^11,12 and observational studies,^13,14 and inadequate scientific evidence to guide treatment decision-making.⁸

In 2020, the Food and Drug Administration (FDA) issued guidance on diversity in clinical trials,¹⁵ stating that some eligibility criteria templates ‘[exclude] certain populations from trials without strong clinical or scientific justification’.¹⁵ To improve cancer care equity, trial participants must represent populations that ultimately might receive interventions under study. Recently, the exclusion of people with disability from trials has attracted attention,^11,16,17 with the FDA noting the potential need for reasonable accommodations to support participation of patients with physical and/or mental disabilities.¹⁵

Oncology clinical trials often exclude patients based on performance status (PS),¹⁸ frequently captured by the Eastern Cooperative Oncology Group (ECOG) Performance Status¹⁹ Scale and Karnofsky Performance Scale (KPS),²⁰ dating to 1948 and 1960, respectively. Both ECOG and KPS privilege work status, ambulation, and ability to perform activities of daily living without supportive services or devices (Table 1). However, many trials narrowly define their study population, limiting participation to patients with good PS scores,²⁰ effectively excluding many disabled people. Given this concern, both the April 2024 FDA draft guidance and 2021 recommendation by the American Society of Clinical Oncology (ASCO) – Friends of Cancer Research collaborative advocate for less restrictive PS thresholds, and the inclusion of patients with ECOG scores = 2 and KPS scores = 60.^22,23

Table 1.

Performance status criteria.

Performance status as defined by ^aKarnofsky et al.²⁴
Definition	%	Criteria
Able to carry on normal activity and to work. No special care is needed.	100	Normal; no complaints; no evidence of disease
	90	Able to carry on normal activity; minor signs or symptoms of disease
	80	Normal activity with effort; some signs or symptoms of disease.
Unable to work. Able to live at home, care for most personal needs. A varying amount of assistance is needed.	70	Cares for self. Unable to carry on normal activity or to do active work.
	60	Requires occasional assistance, but is able to care for most of his needs.
	50	Requires considerable assistance and frequent medical care.
Unable to care for self. Requires equivalent of institutional or hospital care. Disease may be progressing rapidly.	40	Disabled; requires special care and assistance.
	30	Severely disabled; hospitalization is indicated although death not imminent.
	20	Very sick; hospitalization necessary; active supportive treatment necessary.
	10	Moribund; fatal processes progressing rapidly
	0	Dead.
Performance status as defined by the Eastern Cooperative Oncology Group (ECOG)^b
Grade		ECOG
0		Fully active, able to carry on all pre-disease performance without restriction
1		Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light housework and office work
2		Ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours
3		Capable of only limited self-care; confined to bed or chair more than 50% of waking hours
4		Completely disabled; cannot carry on any self-care; totally confined to bed or chair
5		Dead

^aTimmermann.²¹

^bECOG-ACRIN Cancer Research Group.¹⁹

Jaoude et al.¹⁸ found that nearly 40% of clinical trials prior to 2020 required ECOG scores equal or less than 1; however, more recent estimates are not available despite emerging guidance for less restrictive criteria. Furthermore, no prior study has examined other potential criteria that can exclude people with disability more broadly. We used information from Clinicaltrials.gov to explore the use of ECOG and KPS scores in excluding individuals from oncology clinical trials, providing a baseline for assessing how the 2024 FDA draft guidance, if finalized, might affect the inclusion of people with disability in clinical trials.

Methods

Identifying clinical trials

We used the advanced search function in Clinicaltrials.gov to identify clinical trials meeting the following criteria: health area = ‘cancer’; intervention study; at least one US location; subjects aged 18 years or older; start dates between 1 January 2019 and 31 December 2023; Phase III or IV trial; and posted study protocol. The eligibility criteria displayed on individual study web pages on ClinicalTrials.gov are often abstracted and incomplete, as it is the principal investigators’ prerogative to decide what information gets posted on the web page.²⁵ Therefore, we chose to review only studies that have complete protocols that were available as retrievable documents (i.e. that we could download). We focused on Phase III and IV studies because eligibility criteria at these stages inform product labels. A search completed in April 2024 identified 160 studies for screening; screening excluded protocols without at least one US location, paediatric patients only or inclusion of non-cancer conditions (e.g. myasthenia gravis). Ninety-six protocols qualified for our study (see Supplemental Material Appendix A. PRISMA diagram).

Defining disability

In addition to identifying inclusion criteria related to ECOG and KPS (Table 1), we examined trial protocols for other factors that would affect participation by disabled people. We used the World Health Organization’s International Classification of Functioning, Disability and Health (ICF) definition of disability, which conceptualizes disability as an interplay between impairments of body systems or structures and activity or participation limitations.^26,27 An example of a functional eligibility criterion is ‘exclude patients who use wheelchairs’.

Data collection

We reviewed inclusion and exclusion criteria of posted protocols using methods similar to those of DeCormier Plosky et al.¹¹ (see Supplemental Material Appendix B). Here, we reviewed PS thresholds (ECOG and KPS scores), Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria²⁸ and provision of reasonable accommodations. We chose to review CTCAE criteria given that some ‘adverse events’ such as peripheral neuropathy may be associated with pre-existing disability and not necessarily caused exclusively by cancer. Reasonable accommodations include any modification or adjustment (e.g. visual aide) that enable disabled individuals to participate in the trial and do not impose an ‘undue burden’.

Data analysis

We calculated frequency of inclusion of PS criteria (ECOG and KPS thresholds) in eligibility criteria. We used conventional content analysis^29–31 to review miscellaneous criteria pertaining to people with disability.

Results

Studies addressed many cancer types, and 63 (65.6%) included ECOG or KPS score criteria for participation. As shown in Table 2, the most common thresholds for inclusion were ECOG 0 or 1 or equivalent KPS 70 or greater in 42 (43.8%) of studies, and ECOG 0, 1 or 2 or equivalent KPS 60 or greater in 19 (19.8%) of studies. One study required ‘adequate PS’ without specifying score requirements.

Table 2.

Inclusion of patients based on performance status scores.

Performance status	Number of studies (percentage of total studies n = 96)
Mentions ECOG or KPS scores in eligibility criteria	63 (65.6%)
Includes patients with ECOG 0 or 1, or equivalent KPS 70 or greater	42 (43.8%)
Includes patients with ECOG 0, 1 or 2, or equivalent KPS 60 or greater	19 (19.8%)
ECOG	58 (60.4%)
Includes patients with 0 or 1	39 (40.6%)
Includes patients with 0, 1 or 2	18 (18.8%)
Includes patients with 0, 1, 2 or 3	1 (1.0%)
KPS	7 (7.3%)
Includes patients with 50 or greater	1 (1.0%)
Includes patients with 60 or greater	2 (2.1%)
Includes patients with 70 or greater	4 (4.2%)
Includes patients with 80 or greater	1 (1.0%)
CTCAE^a	31 (32.3%)

Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Among studies, 31 (32.3%) specified CTCAE version 5.0 criteria (Table 2). Most CTCAE criteria involved adverse effects of prior treatment. Peripheral neuropathy was cited most frequently (e.g. exclusion criteria describing ‘participants with greater than Grade 1 peripheral neuropathy’). In most studies, investigators had discretion to determine whether signs or symptoms, such as peripheral neuropathy, were treatment related. It was not clear how investigators consider CTCAE adverse events, such as peripheral neuropathy, which may not be exclusively associated with cancer but may be associated with conditions causing pre-existing disability when evaluating participants for study enrolment.

Some protocols excluded people with specific disabilities, such as the following: ‘Patient has used a wheelchair, been bedbound or is unable to walk without assistance from other people every day for the past 7 days (patients are not excluded for the use of walkers or canes)’. ‘Permanent legal blindness in the fellow (non-study) eye’. ‘A history or current evidence of any condition (e.g. hearing impairment), therapy or laboratory abnormality that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator’. Many studies had miscellaneous eligibility criteria that may apply to people with disability, including inability to tolerate imaging, transportation and technology barriers, and concerns about swallowing medication (Table 3). No studies mentioned accommodations that were permitted or provided for participants with any type of impairments.

Table 3.

Examples of miscellaneous criteria.

Oral medication

‘Inability to swallow pills’

‘Ability to take oral medications and willing to record daily adherence to investigational product’

‘Known difficulty in tolerating oral medications …’

‘Is unable to swallow tablets/capsules’.

‘Patients who are not able to swallow a tablet’

‘… inability or unwillingness to swallow pills’

Tolerating imaging

‘Unable to tolerate CT or magnetic resonance imaging (MRI)’

‘Unable to lie flat, still or tolerate a PET/CT scan, or any other condition that would preclude PET/CT imaging’

‘Unwilling or unable to undergo an MRI or CT scan for spleen volume measurement per protocol requirements’

Ability to access electronic applications

‘Patient is able and willing to use the mobile application and connected devices on a daily basis for up to 12 months’

‘Patient is able to complete QoL assessments once every 2 weeks for the first 3 months of the study and monthly thereafter’

‘The patient has a smart phone that can receive SMS text messages and has bluetooth capability that can connect to Fitbit’.

Transportation

‘In the opinion of the enrolling physician, no medical conditions that preclude the subject or the primary caregiver from transportation to and from the outpatient clinical care facility’.

Anticipated need for prolonged hospital stay

‘Anticipated need for inpatient hospitalization or inpatient surgery from Day 1 to Day 57’

‘No history of a clinically significant medical condition anticipated to require intervention during the course of the study participation (e.g. anticipated major elective surgery)’

Discussion

Among almost 100 oncology clinical trials identified on ClinicalTrials.gov, approximately two-fifths excluded individuals with ECOG or KPS scores that are more restrictive than those recommended in 2024 draft FDA guidelines. One-fifth of studies had PS exclusion criteria consistent with proposed FDA guidelines. Multiple studies contained miscellaneous criteria that could potentially exclude people with disability, and none indicated accommodations to facilitate participation of disabled individuals. As noted by the FDA, restrictive PS in eligibility criteria may limit patient enrollment and access to trials, leading to results that do not generalize to patient populations that will ultimately use the drug.²² Our findings raise several points.

First, the majority of recent oncology clinical trials do not comply with an emerging consensus from professional organizations, including ASCO and the FDA, about relaxing PS exclusion criteria. FDA 2024 guidelines recommend including “patients with ECOG PS 2 (or KPS 60–70) … unless there is clinical rationale for exclusion justified by established safety considerations”.²² Prior ASCO guidelines^23,32 concurred that trials should not exclude patients with ECOG PS 2. Concerns about PS criteria include that they are prone to subjectivity and poor inter-rater reliability and do not consider the aetiology of functional impairments. PS determinations have low inter-rater reliability between health care professionals,^33,34 potentially leading to bias that could affect inclusion of patients with borderline scores.

Second, investigators may have concerns about liberalizing PS criteria, notably decreased survival and increased difficulty with obtaining response data from patients with lower PS scores. However, a meta-analysis of randomized controlled trials between 2006 and 2010 found no difference in relative efficacy of novel systemic therapies between patients with excellent (ECOG 0) and reduced (ECOG 2) scores.³⁵ More broadly, some have argued that eligibility criteria are unnecessarily restrictive, limiting generalizability to patient populations that will ultimately be using the treatment.³⁶ Restricting eligibility criteria have three consequences: selective removal of subjects may change overall prognosis; restrictions based on toxicity may alter overall assessment of treatment tolerance; and restrictions may affect assessment of efficacy.³⁷

Third, if trials do include participants with low PS scores and/or functional impairments, accommodations could facilitate adherence to trial procedures; however, we failed to identify any studies that described accommodations for people with disability. Prior studies have found that barriers relating to imaging (e.g. problems positioning patients, inaccessible equipment and failure of clinical staff to seek proactive solutions) can delay cancer diagnoses or treatment for people with disability.^9,10,38,39 Creative efforts to address these problems can reduce barriers to imaging services.⁹ Another reasonable accommodation might address transportation barriers, which are especially problematic for people with disabilities.^40,41 The Multi-Regional Clinical Trials Accessibility by Design Toolkit⁴² suggests that trials should proactively inquire about transportation needs and arrange accessible transportation when feasible. Making recruitment materials accessible and identifying sign language interpreters to assist with informed consent processes can facilitate inclusion for participants who are hard of hearing.⁴³

Fourth, investigators might worry that providing accommodations will increase the size, complexity and costs of already large and expensive trials. Although studies on cost of accommodations for patients in the health care setting are limited, estimates from other settings such as the workplace suggest that accommodations may incur minimal costs. For example, one study suggested that the cost of accommodating scheduling preferences may be minimal,⁴⁴ and nearly half of accommodations for disabled workers have no cost.⁴⁵ Deciding what constitutes a reasonable accommodation is an interactive process where the needs of a patient should be prioritized but a clinician can decide if the accommodation would constitute an ‘undue burden’, in which case an alternative solution should be explored.⁴⁶

Finally, other recommendations for future trials include alternative trial design, adjustment of inclusion criteria for later-stage studies and consideration of other functional assessment tools.^47–49 The FDA recommends consideration of alternative trial designs where patients with ECOG 2–4 can be excluded from the primary analysis of progression-free and overall survival, and evaluated separately in an exploratory cohort with early stopping criteria based on emerging safety data. This would be consistent with FDA 2019 industry guidance which recommended prespecified cohorts with low PS.⁵⁰

Limitations

Given our focus on eligibility criteria, we searched ClinicalTrials.gov for studies with posted protocols, which reduced the number of available studies for review. We did not rely upon the eligibility criteria published on individual study web pages as these abstractions are often incomplete, constrained by character limits, and information may be selectively displayed.⁵¹ Of note, studies with a primary completion date on or after 18 January 2017 are required to post a study protocol only with submission of results.⁵² Our data range of 1 January 2019 to 31 December 2023, therefore, limited our selection to studies that were completed in this timeframe (i.e. not ongoing studies). However, this data range provides more recent estimates of prevalence of PS criteria than those described elsewhere.^18,20

Conclusion

Professional organizations including ASCO and the FDA are moving towards relaxing PS-based exclusion criteria. Oncology clinical trials exclude people with disability, often due to potentially restrictive PS thresholds, vaguely worded accessibility criteria and absence of reasonable accommodations. Our estimates provide a baseline against which to assess how the 2024 FDA draft guidance, if finalized, affects the inclusion of people with disability in oncology clinical trials. Efforts from funding bodies and regulatory agencies are warranted to address exclusion of people with disability in clinical trials and provide reasonable accommodations for study participation.

Supplemental Material

sj-docx-1-ctj-10.1177_17407745241304114 – Supplemental material for Exclusion of people from oncology clinical trials based on functional status

Supplemental material, sj-docx-1-ctj-10.1177_17407745241304114 for Exclusion of people from oncology clinical trials based on functional status by Nicole D Agaronnik, Mary Linton B Peters and Lisa I Iezzoni in Clinical Trials

Footnotes

Acknowledgements

None.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship and/or publication of this article.

Ethical considerations

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

ORCID iD

Nicole D Agaronnik

Data availability statement

Data source: publicly available information from ClinicalTrials.gov.

Supplemental material

Supplemental material for this article is available online.

References

Centers for Disease Control and Prevention. Disability impacts all of us, https://www.cdc.gov/ncbddd/disabilityandhealth/infographic-disability-impacts-all.html (accessed 14 August 2024).

National Institutes of Health. NIH designates people with disabilities as a population with health disparities, https://www.nih.gov/news-events/news-releases/nih-designates-people-disabilities-population-health-disparities (2023, accessed 14 August 2024).

Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities, Division of Human Development and Disability. Disability and Health Data System (DHDS) Data [online], https://dhds.cdc.gov (accessed 30 July 2024).

Iezzoni

Rao

Agaronnik

, et al. Cross-sectional analysis of the associations between four common cancers and disability. J Natl Compr Canc Netw 2020; 18(8): 1031–1044.

Iezzoni

Rao

Agaronnik

, et al. Associations between disability and breast or cervical cancers, accounting for screening disparities. Med Care 2021; 59(2): 139–147.

McCarthy

Ngo

Roetzheim

, et al. Disparities in breast cancer treatment and survival for women with disabilities. Ann Intern Med 2006; 145(9): 637–645.

Iezzoni

Ngo

, et al. Treatment disparities for disabled medicare beneficiaries with stage I non-small cell lung cancer. Arch Phys Med Rehabil 2008; 89(4): 595–601.

Iezzoni

. Cancer detection, diagnosis, and treatment for adults with disabilities. Lancet Oncol 2022; 23(4): e164–e173.

Agaronnik

El-Jawahri

Iezzoni

. Perspectives of patients with pre-existing mobility disability on the process of diagnosing their cancer. J Gen Intern Med 2021; 36(5): 1250–1257.

10.

Agaronnik

El-Jawahri

Lindvall

, et al. Exploring the process of cancer care for patients with pre-existing mobility disability. JCO Oncol Pract 2021; 17(1): e53–e61.

11.

DeCormier Plosky

Ne’eman

Silverman

, et al. Excluding people with disabilities from clinical research: eligibility criteria lack clarity and justification. Health Aff (Millwood) 2022; 41(10): 1423–1432.

12.

Van Spall

HGC

Toren

Kiss

, et al. Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review. JAMA 2007; 297(11): 1233–1240.

13.

Rios

Magasi

Novak

, et al. Conducting accessible research: including people with disabilities in public health, epidemiological, and outcomes studies. Am J Public Health 2016; 106(12): 2137–2144.

14.

Iezzoni

. Tracking disability disparities: the data dilemma. J Health Serv Res Policy 2008; 13(3): 129–130.

15.

US Food and Drug Administration. Enhancing the diversity of clinical trial populations: eligibility criteria, enrollment practices, and trial designs guidance for industry, 2020, https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enhancing-diversity-clinical-trial-populations-eligibility-criteria-enrollment-practices-and-trial

16.

Camanni

Ciccone

Lepri

, et al. ‘Being disabled’ as an exclusion criterion for clinical trials: a scoping review. BMJ Glob Health 2023; 8(11): e013473.

17.

McDonald

Schwartz

Sabatello

. Eligibility criteria in NIH-funded clinical trials: can adults with intellectual disability get in? Disabil Health J 2022; 15(4): 101368.

18.

Abi Jaoude

Kouzy

Mainwaring

, et al. Performance status restriction in phase III cancer clinical trials. J Natl Compr Canc Netw 2020; 18(10): 1322–1326.

19.

ECOG-ACRIN Cancer Research Group. ECOG Performance Status scale, https://ecog-acrin.org/resources/ecog-performance-status/ (2022, accessed 6 June 2024).

20.

Jin

Pazdur

Sridhara

. Re-evaluating eligibility criteria for oncology clinical trials: analysis of investigational new drug applications in 2015. J Clin Oncol 2017; 35(33): 3745–3752.

21.

Timmermann

. Just give me the best quality of life questionnaire’: the Karnofsky scale and the history of quality of life measurements in cancer trials. Chronic Illn 2013; 9(3): 179–190.

22.

US Food and Drug Administration. Cancer clinical trial eligibility criteria: performance status. Draft guidance for industry, IRBs, and clinical investigators, 2024, https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cancer-clinical-trial-eligibility-criteria-performance-status

23.

Kim

Uldrick

Schenkel

, et al. Continuing to broaden eligibility criteria to make clinical trials more representative and inclusive: ASCO-Friends of Cancer Research Joint Research Statement. Clin Cancer Res 2021; 27(9): 2394–2399.

24.

Karnofsky

Abelmann

Craver

, et al. The use of the nitrogen mustards in the palliative treatment of carcinoma. With particular reference to bronchogenic carcinoma. Cancer 1948; 1(4): 634–656.

25.

Protocol registration data element definitions for interventional and observational studies. ClinicalTrials.gov., https://clinicaltrials.gov/policy/protocol-definitions (accessed 30 July 2024).

26.

Centers for Disease Control and Prevention. The ICF: an overview, https://www.cdc.gov/nchs/data/icd/icfoverview_finalforwho10sept.pdf (accessed 14 August 2024).

27.

Bickenbach

Rubinelli

Baffone

, et al. The human functioning revolution: implications for health systems and sciences. Front Sci 2023; 1: 1118512.

28.

US Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, 2017, https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf

29.

Hsieh

Shannon

. Three approaches to qualitative content analysis. Qual Health Res 2005; 15(9): 1277–1288.

30.

Sandelowski

. Whatever happened to qualitative description? Res Nurs Health 2000; 23(4): 334–340.

31.

Sandelowski

. What’s in a name? Qualitative description revisited. Res Nurs Health 2010; 33(1): 77–84.

32.

Kim

Bernstein

Hilsenbeck

, et al. Modernizing eligibility criteria for molecularly driven trials. J Clin Oncol 2015; 33(25): 2815–2820.

33.

Chow

Bruera

Temel

, et al. Inter-rater reliability in performance status assessment among healthcare professionals: an updated systematic review and meta-analysis. Support Care Cancer 2020; 28(5): 2071–2078.

34.

Datta

Ghosal

Daruvala

, et al. How do clinicians rate patient’s performance status using the ECOG performance scale? A mixed-methods exploration of variability in decision-making in oncology. Ecancermedicalscience 2019; 13: 913.

35.

Cheng

Qureshi

Pullenayegum

, et al. Do patients with reduced or excellent performance status derive the same clinical benefit from novel systemic cancer therapies? A systematic review and meta-analysis. ESMO Open 2017; 2(4): e000225.

36.

Collins

Bowman

Landray

, et al. The magic of randomization versus the myth of real-world evidence. N Engl J Med 2020; 382(7): 674–678.

37.

Begg

Engstrom

. Eligibility and extrapolation in cancer clinical trials. J Clin Oncol 1987; 5(6): 962–968.

38.

Agaronnik

El-Jawahri

Kirschner

, et al. Exploring cancer treatment experiences for patients with preexisting mobility disability. Am J Phys Med Rehabil 2021; 100(2): 113–119.

39.

Agaronnik

El-Jawahri

Iezzoni

. Implications of physical access barriers for breast cancer diagnosis and treatment in women with mobility disability. J Disabil Policy Stud 2022; 33(1): 46–54.

40.

Pringle

Doherty

, et al. Addressing transportation barriers in oncology: existing programs and new solutions. Support Care Cancer 2024; 32(5): 317.

41.

Mudaranthakam

Gajewski

Krebill

, et al. Barriers to clinical trial participation: comparative study between rural and urban participants. JMIR Cancer 2022; 8(2): e33240.

42.

Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard. Accessibility by Design (AbD) – a toolkit for inclusion of people with disabilities in clinical research, 2023, https://mrctcenter.org/diversity-in-clinical-research/wp-content/uploads/sites/8/2024/04/2024_04_02-AbD-in-CR-Toolkit_V1.3-with-cover.pdf

43.

Kushalnagar

Nicolarakis

Mirus

, et al. Barriers and facilitators to the inclusion of deaf people in clinical trials. Clin Trials 2023; 20(5): 576–580.

44.

Solovieva

Walls

Hendricks

, et al. Cost of workplace accommodations for individuals with disabilities: with or without personal assistance services. Disabil Health J 2009; 2(4): 196–205.

45.

US Department of Labor announces report finding nearly half of accommodations for disabled workers have no cost, https://www.dol.gov/newsroom/releases/odep/odep20230504 (accessed 14 August 2024).

46.

Eligibility Criteria, 28 C.F.R. Sect. 36.301 (1992).

47.

US Food and Drug Administration. Core patient-reported outcomes in cancer clinical trials. Guidance for industry, 2024. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/core-patient-reported-outcomes-cancer-clinical-trials

48.

Suh

Leblanc

Shelby

, et al. Longitudinal patient-reported performance status assessment in the cancer clinic is feasible and prognostic. J Oncol Pract 2011; 7(6): 374–381.

49.

Repetto

Fratino

Audisio

, et al. Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: an Italian Group for Geriatric Oncology Study. J Clin Oncol 2002; 20(2): 494–502.

50.

US Food and Drug Administration. Adaptive design clinical trials for drugs and biologics guidance for industry, 2019, https://www.fda.gov/regulatory-information/search-fda-guidance-documents/adaptive-design-clinical-trials-drugs-and-biologics-guidance-industry

51.

Tse

Fain

Zarin

. How to avoid common problems when using ClinicalTrials.gov in research: 10 issues to consider. BMJ 2018; 361: k1452.

52.

US Department of Health and Human Services. 42 CFR part 11 clinical trials registration and results information submission, 2016, https://www.ecfr.gov/current/title-42/chapter-I/subchapter-A/part-11

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