Arm 1 participants underwent automated monitoring for pain, whereas arm 2 participants received telerehabilitation, and arm 3 participants received telerehabilitation and pain management. Error bars indicate standard error of the mean.
aPositive effect size for Activity Measure for Postacute Care Basic Mobility and EQ-5D-3L Index scores indicates a better status and negative effect size indicates a worse state.
bNegative total pain interference and average pain scores indicate pain reduction.
eAppendix. Cope Intervention
eFigure 1. Standing Calf Raise
eFigure 2. Highlights for Physical Therapist Instructing COPE Program
eTable. Baseline Sociodemographic, Clinical, and Cancer-Related Characteristics of the Study Sample
Data Sharing Statement
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Cheville AL, Moynihan T, Herrin J, Loprinzi C, Kroenke K. Effect of Collaborative Telerehabilitation on Functional Impairment and Pain Among Patients With Advanced-Stage Cancer: A Randomized Clinical Trial. JAMA Oncol. 2019;5(5):644–652. doi:10.1001/jamaoncol.2019.0011
Does collaborative telerehabilitation with or without pharmacological pain management for patients with functional impairment and late-stage cancer improve function, lessen pain, and reduce requirements for inpatient care?
In this 3-arm randomized clinical trial of 516 patients, telerehabilitation with physical therapy–directed pain management modestly improved function, pain, and quality of life, and reduced hospital length of stay and use of postacute care facilities. Telerehabilitation with nurse-directed pharmacological pain management also improved pain and reduced use of postacute care facilities.
Collaborative telerehabilitation that integrates impairment and pain management may be considered a viable component of comprehensive cancer care for patients with advanced-stage cancer experiencing mild disability.
Most patients with advanced-stage cancer develop impairment and pain-driven functional losses that jeopardize their independence.
To determine whether collaborative telerehabilitation and pharmacological pain management improve function, lessen pain, and reduce requirements for inpatient care.
Design, Setting, and Patients
The Collaborative Care to Preserve Performance in Cancer (COPE) study was a 3-arm randomized clinical trial conducted at 3 academic medical centers within 1 health care system. Patient recruitment began in March 2013 and follow-up concluded in October 2016. Participants (N = 516) were low-level community or household ambulators with stage IIIC or IV solid or hematologic cancer.
Participants were randomly assigned to the (1) control arm, (2) telerehabilitation arm, or (3) telerehabilitation with pharmacological pain management arm. All patients underwent automated function and pain monitoring with data reporting to their care teams. Participants in arms 2 and 3 received 6 months of centralized telerehabilitation provided by a physical therapist-physician team. Those in arm 3 also received nurse-coordinated pharmacological pain management.
Main Outcomes and Measures
Blinded assessment of function using the Activity Measure for Postacute Care computer adaptive test, pain interference and average intensity using the Brief Pain Inventory, and quality of life using the EQ-5D-3L was performed at baseline and months 3 and 6. Hospitalizations and discharges to postacute care facilities were recorded.
The study included 516 participants (257 women and 259 men; mean [SD] age, 65.6 [11.1] years), with 172 randomized to 1 of 3 arms. Compared with the control group, the telerehabilitation arm 2 had improved function (difference, 1.3; 95% CI, 0.08-2.35; P = .03) and quality of life (difference, 0.04; 95% CI, 0.004-0.071; P = .01), while both telerehabilitation arms 2 and 3 had reduced pain interference (arm 2, −0.4; 95% CI, −0.78 to −0.09; P = .01 and arm 3, −0.4; 95% CI, −0.79 to −0.10; P = .01), and average intensity (arm 2, −0.4; 95% CI, −0.78 to −0.07; P = .02 and arm 3, −0.5; 95% CI, −0.84 to −0.11; P = .006). Telerehabilitation was associated with higher odds of home discharge in arms 2 (odds ratio [OR], 4.3; 95% CI, 1.3-14.3; P = .02) and 3 (OR, 3.8; 95% CI, 1.1-12.4; P = .03) and fewer days in the hospital in arm 2 (difference, −3.9 days; 95% CI, −2.4 to −4.6; P = .01).
Conclusions and Relevance
Collaborative telerehabilitation modestly improved function and pain, while decreasing hospital length of stay and the requirement for postacute care, but these outcomes were not enhanced with the addition of pharmacological pain management.
ClinicalTrials.gov identifier: NCT01721343
Disabling functional losses degrade quality of life (QoL) and increase health care use among patients with advanced-stage cancer.1-3 Hospitalizations, which account for one-third of direct cancer costs, are more frequent, longer, and more likely to result in acute hospitalizations, long-term care, and inpatient postacute care among patients with impaired mobility.4,5 Although rehabilitation services and conditioning activities can mitigate functional losses,6 few patients with cancer receive this care and fewer still receive it in the early stages of disability when treatments are more effective.1 Factors constraining clinicians’ ability to mitigate functional decline include limited patient access to center-based programs, lack of clinician and patient stakeholder awareness of rehabilitation’s potential benefits, and an insufficient cancer rehabilitation workforce.7
Collaborative approaches, exemplified by the Collaborative Care Model (CCM), effectively deliver supportive care in primary and specialty settings to improve mood, pain, and other outcomes.8-10 A telecare iteration of the CCM was shown to neutralize access barriers and effectively improve depression and pain outcomes among patients with cancer.11,12 Pain is relevant to functional disability among patients with cancer given that it has been causally associated with functional decline,13 is frequently severe and undertreated,14 and limits patients’ engagement with rehabilitation services.15 In fact, prior research has shown pain to be among the most potent and remediable sources of functional loss in patients with late-stage cancer.16
Despite the CCM’s robust benefits across delivery modes, populations, and treatment targets, the model has not been extended to function-directed care. Furthermore, it is unclear whether the effects achieved with center-based cancer rehabilitation programs can be matched with a more accessible telecare-based approach.6 The COllaborative Care to Preserve PErformance in Cancer (COPE) randomized clinical trial was designed to address this knowledge gap. Comparison of arms 1 and 2 assessed the effect of a CCM-based, centralized telerehabilitation intervention on function, pain, and utilization. Comparison of arms 1 and 3 assessed whether the systematic integration of pharmacological pain management had an influence on these effects given that 1 report suggested that up to two-thirds of trial participants would experience at least moderate pain.17
Details of the 3-arm, single-blind, randomized COPE trial design have been previously described.18 Potentially eligible patients were identified through serial searches of the Mayo Clinic electronic health records (EHRs) from the Rochester, Minnesota, Jacksonville, Florida, and Scottsdale, Arizona campuses (3 large medical centers within a single health care system and collectively comprising a National Cancer Institute–designated comprehensive cancer center) performed between March 2013 and March 2016. Data analyses were performed from April 2017 to February 2018. The EHRs of patients assigned an ICD-9 or ICD-10 code for solid tumor, myeloma, myelodysplastic syndrome, or lymphoma on 2 occasions during the 6 months preceding the search were reviewed for eligibility criteria and pathological confirmation of cancer diagnosis and stage. Eligible patients were mailed a brochure describing the trial, a consent document, and an opt-out postcard. Those who did not opt-out within 2 weeks were contacted by telephone, screened for eligibility, and invited to participate. Once a signed written consent was received, patients completed a baseline interview and were randomly allocated to treatment arms in a 1:1:1 ratio by a computer algorithm using the Pocock and Simon19 approach to balance the marginal distributions of stratification factors: cancer type and stage, sex, presence of an in-home caregiver, and pain rating. The study coordinator called the Mayo Clinic Cancer Center Clinical Research Office to learn participants’ group assignments. All outcome assessors remained blinded. The study was approved by the Mayo Clinic Institutional Review Board and was registered on ClinicalTrials.gov (NCT01721343). Trial characteristics, eligibility criteria, intervention, outcomes, and planned analyses were not altered after the trial commenced. Recruitment ended after reaching the accrual target of 516 participants. Data collection from participants was completed in October 2016. The trial protocol is outlined in Supplement 1.
Eligible patients were required to have pathologically confirmed stage IIIC or IV solid or hematologic cancer and moderate functional impairment defined as an Activity Measure for Postacute Care (AM-PAC) basic mobility score between 53 and 66, which is a range that includes low-level community to intermediate-level household ambulation and the need for increasing assistance with activities of daily living.20 Eligible patients were 18 years or older and fluent in English, with a life expectancy of more than 6 months (determined through EHR review and the judgment of 2 medical oncologists [T.M. and C.L.] who have both been in practice for >30 years) and sufficient auditory acuity for telephone conversation. Exclusion criteria included a major surgical procedure or receipt of neoadjuvant therapy within the past 2 months, impaired cognition (Folstein Mini-Mental Status Examination score ≤25), paralysis of 2 or more limbs, chronic noncancer pain rated higher than 5 of 10, and moderate or severe depression (Patient Health Questionnaire-9 score >10).
A research assistant who was blinded to treatment arm assessed outcomes at baseline, 3 months, and 6 months by telephone interview. Up to 6 contact attempts were made over 2 weeks for follow-up assessments.
Of the 2 outcomes targeted by the COPE intervention, function was primary and pain was secondary. Physical function was assessed with the robustly validated AM-PAC basic mobility computer adaptive test (CAT).21,22 The AM-PAC-CAT was chosen for its superior precision and efficiency relative to legacy and fixed-length tools and because it yields ratio data.23,24 Moreover, the AM-PAC-CAT is the only functional assessment tool that has been shown to be responsive among functionally impaired patients with advanced-stage cancer.16 Its minimal clinically important difference (MCID) for improvement in this population is 1,16 which agrees with other reports.25 Pain was assessed with the Brief Pain Inventory (BPI) average and total interference scores. Reported BPI interference score MCIDs among patients with metastatic cancer range from 0.2 to 1.0 or more.26 Quality of life was assessed with the 5-item EQ-5D-3L, which has an MCID of 0.04 or higher among chronically ill patients.27-29 Both the BPI and EQ-5D-3L have support for validity in populations with advanced cancer.30-32 The trial initially included a more extensive panel of secondary outcomes.18 However, data collection during the first months revealed that about 20% of participants declined to complete it. A multi-stakeholder consensus process guided reduction to the parsimonious panel that was continued throughout the trial.
Complementary approaches were used to ascertain overnight hospitalizations and discharge locations. Participants completed a validated care utilization report during the 3- and 6-month interviews.33 Hospitalizations that occurred at a Mayo Clinic hospital, including its 5-state health care system, were identified using an electronic search tool and administrative databases.34 Additionally, hospitalizations were sought by reviewing outside records uploaded into the Mayo Clinic’s EHR and by querying facilities when requesting records for care utilization report events. Records for all hospitalizations were obtained and abstracted by 2 blinded research assistants who determined length of stay, discharge location, and whether an admission was preplanned for cancer treatment.
The 3 COPE trial arms built sequentially. Patients participated in the trial for 6 months. Arm 1 was a control condition of automated monitoring for pain using 3 items from the PEG (average pain intensity [P], interference with enjoyment of life [E], interference with general activity [G]) scale35 and for function using 5 items from the AM-PAC basic mobility bank. Arm 1 participants were encouraged to report on alternate weeks for the first month of the trial period and monthly thereafter. Assessments used interactive voice recognition telephone calls or web-based surveys. Summary reports were provided to the primary, hematologic, or oncologic care team that participants identified as coordinating their care.
Arm 2 included remote monitoring as in arm 1 with the addition of an individualized physical conditioning program delivered telephonically by 2 physical therapist fitness care managers (FCMs) with 15 years or more of specialization in cancer rehabilitation. The FCM instructed patients in an incremental pedometer-based walking program36 and a resistive exercise program (Rapid Easy Strength Training or REST), which have been proven effective.37 The FCMs screened participants for physical impairments and individualized their REST programs as required. Fitness care managers received participants’ feedback on pain, as well as function. They encouraged the use of compensatory strategies and initiated rehabilitative analgesic modalities when indicated. The FCMs communicated concerns and recommendations to participants’ oncologic, hematologic, or primary care teams as required.
Participants were referred to local, outpatient physical therapists to further adapt their conditioning and analgesic regimens and to address physical impairments. The FCMs supported the local, generalist physical therapists to ensure REST fidelity and to individualize cancer-specific precautions. Participants set their own step-count goals with encouragement from the FCM to advance if they met their step goal 5 of 7 days per week. Participants’ REST programs were also advanced in terms of repetitions and resistance contingent on adherence and tolerance. Automated monitoring of arm 2 participants, in addition to the arm 1 pain and function reporting, included logging of step counts and REST sessions, and the option to request an FCM call. Arm 2 participants reported weekly for the first month to promote use of the system. Thereafter, they reported weekly if feasible, but FCMs endorsed every other week and monthly reporting if participants felt burdened. Fitness care managers received an email alert when participants did not complete their scheduled assessments, performed fewer than the recommended 4 REST sessions per week, or reported loss of function or increased pain. The FCMs were able to track participants’ longitudinal reporting on a web-based dashboard. The FCMs reviewed information on new and nonresponding participants with a cancer rehabilitation physician specialist (A.L.C.) during weekly meetings.
Arm 3 added pharmacological pain management directed by a nurse pain care manager (PCM), identical to the Indiana Cancer Pain and Depression trial’s CCM.12 Automated monitoring of arm 3 participants differed only in the option to request a PCM call. The arm 3 FCM and PCM components of the study were initially designed to function separately with minimal contact. However, multiple, at times redundant, calls from the FCMs and PCM proved burdensome to participants. Therefore, in the second month of the trial, the arm 3 intervention was altered so that only the PCM responded to email pain alerts (PEG scores >3) and addressed pain. The PCM tracked pain reports longitudinally and provided treatment recommendations to study participants’ oncologic, hematologic, or primary care teams via telephone or fax communication. The PCM was supervised by a general internist (K.K.) and a palliative care physician/medical oncologist (T.M.) during weekly telephone calls. Additional specifics regarding the telerehabilitation arms are described in the eAppendix and eFigures 1 and 2 in Supplement 2.
The FCMs reviewed treatment reports for all arm 2 and arm 3 physical therapy sessions. They recorded fidelity to the REST framework and any additional treatments to address physical impairments and pain using checklists. The duration of FCM and PCM participant contacts were recorded along with participants’ interactions with the automatic monitoring system. Analgesic consumption was electronically abstracted from the Mayo Clinic EHR at the time of participants’ last encounter during the study to create variables for oral morphine equivalents, coanalgesics (count), and nonopioids (binary).
The study was initially powered for an overall test using a linear contrast across the 3 ordered arms. However, when the FCM and PCM components were integrated in arm 3, the power analysis was revised to detect clinically significant differences in the primary outcome; physical function (AM-PAC-CAT basic mobility) between arms 1 and 2 and between arms 1 and 3 were compared using 2 simultaneous 2-sided, 2-sample t tests at a combined significance level of 5% or a Sidak corrected level of 2.5%. It was determined that 138 participants per group would provide 80% power to detect a between-group difference of 1.4, roughly 0.4 SD. The AM-PAC-CAT’s MCID for improvement in the COPE trial’s target trait range and population is 1.16 Enrollment of 172 patients per group allowed for an attrition rate of up to 20%. Analyses were based on intention to treat in all randomized participants.
Descriptive statistics for baseline variables included proportions for binary variables and means and SDs for continuous variables. Baseline between-group differences were assessed with 2-tailed χ2 and Fisher exact tests and linear regression. For the primary and secondary outcomes, we assessed group differences over the 6 months of the trial using mixed-effects model repeated measures analysis, which included a random effect for patient, a fixed effect for measurement point (3 months or 6 months), and adjustment for age, sex, baseline value of the outcome variable, cancer type, cancer stage (IV vs other), and time. To improve interpretation of effects across outcomes, each effect was first standardized to have a mean of 0 and a standard deviation of 1; we also report effects in original units. To assess the effect of intervention on whether patients were hospitalized, we used a χ2 test, and we assessed the effect on number of hospitalizations using a negative binomial model, with an offset for number of days of follow-up. For patients who had at least 1 hospitalization, we assessed the effect of the interventions on the total number of days in hospital, discharge status (home vs institution), and planned admission status using mixed-effect Poisson (days in hospital) and logistic models (discharge status, planned status) with random effects for patient. We used multiple imputation to account for missing data and risk adjusters. Post hoc 2-tailed χ2 and Fisher exact tests and linear regressions were used to compare use of rehabilitative and analgesic pain treatments across the arms. Analyses were performed using Stata version 15.1 (StataCorp).
Figure 1 outlines the patient participation in the COPE trial. Letters were sent to 7746 patients culled from 19 460 patients identified through EHR search. After eligibility interviews with 1347 responding patients, 516 were enrolled (257 women and 259 men; mean [SD] age, 65.6 [11.1] years), with 172 randomized to each of the trial arms. Seven (4.1%) participants in the control arm, and 5 (2.9%) participants in each of the telerehabilitation arms withdrew consent, and 11 (6.4%), 13 (7.6%), and 15 (8.7%) died during the study in arms 1, 2, and 3, respectively. Among the surviving members of the study cohort who did not withdraw consent, response rates were high: 469 of 481 (97.5%) at month 3 and 442 of 454 (97.4%) at month 6 and were similar across the arms.
Baseline characteristics were balanced between the groups and are described in the eTable in the Supplement. Two hundred fifty-seven participants (49.8%) were women, and most (410 of 516 [79.5%] patients) were receiving disease-directed treatment at study enrollment. Local, nonMayo oncology and hematology care teams in 15 states directed treatment for 289 of 516 (56%) participants. Ninety-three Mayo Clinic–based hematology-oncology clinicians cared for the remaining 227 of 516 (44%) participants. Baseline primary and secondary outcomes were similar across the study arms.
Figure 2 illustrates the change in mean AM-PAC-CAT basic mobility scores from baseline. Figure 3 summarizes the effects of telerehabilitation on patient-reported outcomes expressed as standardized effect sizes and coefficients. The arm 2 telerehabilitation group had greater improvement in function than the control arm 1 (between-group difference 1.3; 95% CI, 0.08-2.35; P = .03), a difference exceeding the AM-PAC-CAT’s MCID of 1.16 The AM-PAC-CAT scores did not differ significantly between arms 1 and 3. Relative to control, both telerehabilitation interventions significantly improved pain interference (arm 2, −0.4; 95% CI, −0.78 to −0.09; P = .01 and arm 3, −0.4; 95% CI, −0.79 to −0.10; P = .01), and average pain intensity (arm 2, −0.4; 95% CI -0.78 to −0.07; P = .02 and arm 3, −0.5; 95% CI, −0.84 to −0.11; P = .006). The EQ-5D-3L scores improved significantly for the telerehabilitation arm 2 but not for the telerehabilitation plus pain management arm 3.
The Table summarizes hospitalization outcomes. Total hospital days among control arm 1 participants (335 days) were 57% higher than arm 2 participants (213 days), and 18% higher than arm 3 participants (284 days). This reduction was owing to shorter rather than fewer hospitalizations in the telerehabilitation arms. Mean (SD) lengths of stay were 7.4 (9.3), 3.5 (4.3), and 5.0 (7.2) days, for arms 1, 2, and 3, respectively, and were significantly shorter in arm 2 compared with arm 1 (P = .01). Hospitalized telerehabilitation participants were significantly more likely to be discharged home than patients in the control group (odds ratio [OR], 4.3; 95% CI, 1.3-14.3; P = .02 vs OR, 3.8; 95% CI, 1.1-12.4; P = .03 in arms 2 and 3, respectively). A numerically higher proportion of planned hospitalizations were noted in the telerehabilitation arms, but these differences did not reach statistical significance. Eighty-five (52%) of 163 hospitalizations occurred at Mayo Clinic facilities.
Automated monitoring contacts were similar across arms 1, 2, and 3 with respect to mean frequency [SD] (10.3 [4.4], 10.7 [5.2], and 10.2 [4.5]) and the proportion of patients using web-based instead of interactive voice recognition reporting (66.4%, 73.6%, and 69.1%, respectively). The frequency of FCM contacts were comparable in arms 2 and 3 (7.6 [2.9]; range, 1-21 vs 7.2 [3.1]; range, 1-22), with a duration of 16.2 minutes (15.2; range, 1-124) for arm 2 and 16.6 minutes (15.4; range, 1-87) for arm 3. The FCMs coordinated participants’ visits to 173 different local physical therapists for 111 arm 2 and 110 arm 3 participants, who had an average (SD) of 5.8 (5.9) and 5.2 (8.1) local physical therapy visits, respectively. Patient care manager contacts averaged 4.2 per arm 3 participant (SD, 3.4; range, 1-16) and lasted a mean of 9.7 minutes (SD, 8.7; range, 3-90). Opioid and coanalgesic use were highest in arm 3, but intergroup differences did not reach statistical significance. Arm 2 participants relative to those in arm 3 received significantly more rehabilitative treatments that targeted pain, including regional therapeutic exercise (20.9% vs 11.1%, P = .01), and physical/energetic modalities (18.6% vs 9.3%, P = .01). No adverse effects were reported for participants of any study arm.
The systematic and effective delivery of function-directed care has proven elusive among patients with cancer and chronic diseases owing to a lack of delivery models that match patients’ limitations and needs. By leveraging an ample precedent for the successful extension of the CCM to novel targets and populations,8,9,38,39 the COPE trial established the potential usefulness of the CCM in addressing this deficit. Although modest, the COPE interventions’ effect sizes of 0.23 for mobility and −0.24 for pain are nonetheless notable given the remote, low-touch delivery; the known positive effect of the control condition40; and the trial’s vulnerable, high-needs participants. Furthermore, our findings agree with reports suggesting that surprisingly modest functional losses and gains among individuals with borderline dependency, the demographic targeted in the COPE trial, can profoundly affect their requirement for inpatient care.41,42 The difference of 1.4 in an AM-PAC-CAT score can be used to distinguish individuals who are able to ascend stairs, transfer, and/or ambulate independently from those who are not.20
Center-based exercise interventions have yielded larger effect sizes among patients with late-stage cancer but have been hampered by drop-out rates exceeding 40%,43,44 which highlights the tension between effectiveness and tolerability. The COPE trial’s high retention rate—only 3% of telerehabilitation recipients withdrew consent—suggests that higher exercise intensity may have been tolerated. Further research is needed to inform efforts to balance patient centricity with optimized functional benefit. The convenience of telerehabilitation and the expanded reach that it offers a limited pool of cancer rehabilitation specialists are compelling benefits.
Our finding of reduced hospital use among participants in the telerehabilitation arms adds to growing evidence that proactively addressing functional impairment among vulnerable patients reduces hospital utilization.37 Although strongly associated with health care use,45 functional impairment has been limitedly targeted in efforts to reduce overall costs of care.46 Reducing the requirement for institutional care among patients with late-stage cancer has the potential for high financial return given that hospitalizations account for a large proportion of health care spending in this population,47 drive regional variation in costs of care,48 and are not associated with survival or QoL.49,50
Telerehabilitation with pharmacological pain management was less effective in improving function, which was an unexpected finding, as was the equal effectiveness of the rehabilitative (arm 2) and pharmacological (arm 3) approaches in controlling pain. Post hoc analyses suggested that greater reliance on nonpharmacological rehabilitation pain management approaches, in lieu of opioids and coanalgesics, as well as the more seamless integration of pain- and function-directed treatments that characterized the arm 2 intervention may have contributed to the differences in outcomes between the intervention arms. However, these findings require confirmation.
The COPE trial’s strengths include its large size, low dropout rate, and nearly complete reporting rates, which suggest high internal validity. However, the sample’s racial homogeneity and recruitment from a single, academic health care system, as well as the near universal availability of an in-home caregiver, constrain generalizability. The inclusion of a performance-based functional outcome measure may have afforded better discrimination; however, reports suggest that patient-reported outcomes are more responsive and less prone to ceiling effects than objective functional assessments, particularly when delivered via CAT platforms.22,51
Collaborative telerehabilitation that combined remote and center-based care improved function, pain, and QoL and reduced hospital length of stay and the need for postacute care among patients with advanced-stage cancer and functional disability. Emphasis on rehabilitative rather than pharmacological pain management approaches may partially mediate these benefits and warrants further study.
Accepted for Publication: December 18, 2018.
Corresponding Author: Andrea L. Cheville, MD, MSCE, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (firstname.lastname@example.org).
Published Online: April 4, 2019. doi:10.1001/jamaoncol.2019.0011
Author Contributions: Dr Herrin had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Cheville, Moynihan, Loprinzi, Kroenke.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Cheville.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Cheville, Herrrin.
Obtained funding: Cheville.
Administrative, technical, or material support: Kroenke.
Study Supervision: Moynihan.
Conflict of Interest Disclosures: Dr Cheville reports grants from the National Cancer Institute during the conduct of the study. Dr Loprinzi reports grants from that National Institutes of Health during the conduct of the study. Dr Kroenke reported grants from Indiana University during the conduct of the study. No other disclosures were reported.
Funding/Support: Dr Cheville’s research was supported by National Cancer Institute grant R01 CA163803.
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 3.
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