Trial Protocol and Statistical Analysis Plan
eAppendix A. Patient Characteristics
eAppendix B. Educational Booklet (FOLFIRI)
Data Sharing Statement
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Enzinger AC, Uno H, McCleary N, et al. Effectiveness of a Multimedia Educational Intervention to Improve Understanding of the Risks and Benefits of Palliative Chemotherapy in Patients With Advanced Cancer: A Randomized Clinical Trial. JAMA Oncol. 2020;6(8):1265–1270. doi:10.1001/jamaoncol.2020.1921
Does a video/booklet intervention that integrates authentic patient narratives to convey palliative chemotherapy risks and benefits improve patients’ understanding that cure is very unlikely?
In this multicenter randomized clinical trial involving 186 patients with metastatic colorectal cancer or locally advanced or metastatic pancreatic cancer initiating palliative chemotherapy, providing a regimen-specific chemotherapy educational video/booklet did not alter patients’ expectations of cure. Despite highlighting prognostic information, it did not increase distress.
Providing a palliative chemotherapy educational video/booklet did not meaningfully improve patients’ understanding of treatment risks and benefits, suggesting that future studies would need to examine intervention modifications or an alternative delivery strategy to improve outcomes.
Despite requirements of informed consent, patients with advanced cancer often receive palliative chemotherapy (PC) without understanding that the likelihood of cure is remote.
To determine whether a PC educational video and booklet at treatment initiation could improve patients’ understanding of its benefits and risks.
Regimen-specific PC videos and booklets presenting information about logistics, potential benefits, life expectancy (optional), adverse effects, and alternatives. Videos featured authentic patients sharing diverse experiences. After receiving treatment recommendations, research assistants distributed materials to patients for independent review.
Design, Setting, and Participants
Multicenter randomized clinical trial of patients with advanced colorectal or pancreatic cancer starting first-line or second-line PC in 5 US cancer centers with enrollment from June 2015 to September 2017 and follow-up to December 2019.
Main Outcomes and Measures
The primary outcome was accurate expectations of chemotherapy benefits at 3 months, defined as responding “not at all likely” to “What is your understanding of how likely the chemotherapy is to cure your cancer?” (from the Cancer Care Outcomes Research and Surveillance study). Secondary outcomes included understanding of adverse effects, decisional conflict (SURE test), regret (Decisional Regret Scale), and distress (Functional Assessment of Cancer Therapy–General emotional well-being subscale).
Among 186 patients with advanced colorectal or pancreatic cancer who were starting first-line or second-line PC (94 randomized to usual care, 92 to intervention; mean [SD] age, 59.3 [12.6] [range, 28-86] years; 107 [58%] male; 118 [63.4%] colorectal and 68 [36.6%] pancreatic cancer), most patients wanted “a lot” of information or “as much information as possible” about adverse effects (149, 80.1%), likelihood of cure (148, 79.6%), and prognosis (148, 79.6%). Among the intervention arm, 59 (78%) reviewed the booklet and 30 (40%) reviewed the video within 2 weeks. The primary outcome did not differ between intervention and control arms (52.6%; 95% CI, 40.3%-65.0%; vs 55.5%; 95% CI, 45.1%-66.0%). Accurate adverse effect understanding was more common among intervention than control patients (56.0%; 95% CI, 44.3%-67.7%; vs 40.2%; 95% CI, 29.5%-50.9%; P = .05), although this did not meet the threshold for statistical significance. The intervention did not increase distress, despite frank prognostic information. Other secondary outcomes were similar.
Conclusions and Relevance
Provision of an educational video and booklet did not alter patients’ expectation of cure from PC. Alternative delivery strategies, such as integration with nurse teaching, could be explored in future studies.
ClinicalTrials.gov Identifier: NCT02282722
Patients with advanced cancer often receive palliative chemotherapy (PC) without the core understanding necessary for an informed decision. In the Cancer Care Outcomes Research and Surveillance (CanCORS) study,1 81% and 69% of patients with advanced colorectal and lung cancer, respectively, did not understand that chemotherapy was very unlikely to achieve cure. Other studies confirm pervasive optimism about the ability of chemotherapy to cure or control cancer and prolong life.2,3 These misconceptions undermine the validity of informed consent and have been linked to burdensome end-of-life care.4
Although most patients want comprehensive information about chemotherapy outcomes, specific benefits (eg, response rates, prognosis) are frequently omitted from the consent process.5 Resources available to support informed consent (ie, consent documents and chemotherapy educational materials) do little to fill these gaps and represent an attractive target for intervention. We report a multicenter randomized clinical trial testing a regimen-specific PC educational intervention that leveraged authentic patient voices to convey its risks and realistic benefits. We hypothesized that providing this intervention would improve patients’ understanding.
The study was approved by the Dana-Farber/Harvard Cancer Center Institutional Review Board and the institutional review boards for each participating site and recruited from 5 major US cancer centers (trial protocol in Supplement 1). Eligible patients had metastatic colorectal cancer or locally advanced or metastatic pancreatic cancer and were considering first-line or second-line PC (eAppendix A in Supplement 2). Exclusion criteria included age younger than 21 years, inability to speak English, cognitive impairment, or any plan for curative surgery (eg, for oligometastatic colorectal cancer). After receiving a chemotherapy recommendation, a trained research assistant approached patients for participation and obtained written informed consent. Patients receiving first-line therapy could also enroll; however, they were not randomized until a second-line decision.
We developed a suite of educational booklets and videos, each describing a standard regimen used to treat advanced colorectal or pancreatic cancer.6 Tools reviewed infusion logistics, treatment purpose, potential benefits, adverse effects, and alternatives. Narrated by oncologists, each 22- to 29-minute video featured several patients describing authentic experiences. Tools were direct about the noncurative potential of PC and described specific benefits, including response rates and optional life-expectancy statistics (eAppendix B in Supplement 2; https://vimeo.com/387430409).
Participants were randomized 1:1, without blinding, to usual care or intervention, stratified by line of therapy (Figure). Patients in the intervention group were given the appropriate study booklet by a research assistant, with a link to a video (including password) that could be reviewed on a study tablet in the clinic or from home. Intervention review was neither mandated nor incentivized, a pragmatic design chosen to minimize burden and respect patient autonomy. Participants in the usual care group received site-specific standard educational materials at the discretion of the treating physician.
Patients completed surveys at baseline, postdecision (2-4 weeks), and follow-up (8-12 weeks). At baseline, clinical information was abstracted from the medical record; patients reported race/ethnicity, sociodemographic characteristics, and how much information they wanted about chemotherapy adverse effects, likelihood of cancer control, cure, and influence on length of life (on a 5-point Likert scale from no information to as much as possible). Postdecision, patients reported use of and satisfaction with the intervention and the standard materials (1-10 scale).
Our primary outcome was accurate expectation of chemotherapy benefits at follow-up, defined as responding “not at all likely” to “How likely do you think that chemotherapy is to cure your cancer?” (with answer options of very likely, somewhat likely, a little likely, not at all likely, or don’t know). Derived from the CanCORS study, this outcome was chosen for its relevance to informed decision-making and associations with end-of-life care.4 Patients were asked about the goal(s) of chemotherapy according to their doctor: cure, control cancer, improve symptoms, prolong life, or other. Postdecision, patients also reported how likely chemotherapy was to control cancer growth and cause nausea/vomiting, diarrhea, neuropathy, and hair loss. Accurate adverse effect understanding was determined by comparing participants’ responses to the adverse effect profile of their regimen, as prespecified. The Control Preferences Scale assessed whether patients achieved their preferred decision-making role7; a modified SURE test assessed decisional conflict8; and 5 items from the Patient Assessment of Cancer Communication Experiences (PACE) scale assessed communication satisfaction.9 The Decisional Regret Scale Regret assessed regret10; the Functional Assessment of Cancer Therapy–General (FACT-G) emotional well-being subscale assessed distress.11
Differences in dichotomous and categorical outcomes were analyzed using Fisher exact, χ2, Wilcoxon, and analysis of variance (ANOVA) tests. Two-sided P values were considered significant if less than .05. To mitigate bias from missing data, prespecified analyses of primary and secondary outcomes employed multiple imputation by chained equations (missing-at-random assumption). Results were integrated from 10 imputed data sets (including primary/secondary outcomes, age, sex, race, cancer diagnosis, and therapy line) using Rubin’s rule.12 The planned accrual of 194 participants provided 80% power, with a 2.5% 1-sided type I error, to detect a 50% relative increase in our primary outcome presuming accurate expectations of 40%. Statistical analyses were conducted using R, version 3.5.1 (R Foundation for Statistical Computing).
Between June 2015 and September 2017, 186 patients were enrolled, randomized, and completed at least 1 assessment (Figure). Mean (SD) age was 59.3 (12.6) (range, 28-86) years, and 107 (58%) were male. Patients were largely white and highly educated; 118 (63.4%) had colorectal cancer and 68 (36.6%) had pancreatic cancer; 79.7% were considering first-line therapy (eAppendix A in Supplement 2). At baseline, most patients wanted “a lot” of information or “as much information as possible” about chemotherapy adverse effects (149 of 186, 80.1%), likelihood of cure (148 of 186, 79.6%), cancer control (156 of 186, 83.9%), and influence on life expectancy (148 of 186, 79.6%).
Postdecision, 59 of 74 patients (78%) in the intervention group had reviewed the booklet, and 30 of 73 (41%) had reviewed the video; 47 of 79 patients (59%) in the usual care group had reviewed standard educational materials. Satisfaction was similar for the intervention materials and standard materials (mean [SD], 7.8 [1.8] vs 7.9 [1.7]; P = .70).
The proportion of patients with an accurate expectation of chemotherapy benefits did not differ between the intervention and usual care groups (52.6%; 95% CI, 40.3%-65.0%; vs 55.5%; 95% CI, 45.1%-66.0%) (Table 1 and Table 2). The likelihood of accurate adverse effect understanding was higher in the intervention arm than the control arm (56.0%; 95% CI, 44.3%-67.7%; vs 40.2%; 95% CI, 29.5%-50.9%; P = .05), although this did not meet the threshold for statistical significance. Distress and other secondary outcomes did not differ.
Providing PC educational videos/booklets featuring authentic patient narratives did not alter patients’ expectations of cure; modest improvements in adverse effect knowledge were not statistically significant. Despite explicit prognostic information, the intervention was favorably received and did not increase distress.
What explains these results? Although a third of patients indicated that chemotherapy might cure their cancer, only 10% cited cure as their oncologists’ treatment goal. Expectations for cure may not represent misunderstandings (our intervention target), but alternative factors such as hope or a desire to “be positive.” Second, participants were recruited from academic centers, and most were highly educated. Educational interventions may be more impactful in other settings. Third, intervention uptake (particularly the video) was low in the absence of incentives or structured processes to encourage viewing. Although this pragmatic approach mirrors routine practice, alternative strategies (eg, integration with nurse-led teaching) or delivering the intervention later in the disease trajectory might have been more effective.
Our study highlights the difficulty of improving PC informed decision-making, particularly curability understanding. None of the 3 randomized studies of PC educational interventions/decision aids affected their primary outcomes of decision-making quality,13-15 and only 1 demonstrated delayed (but not immediate) knowledge gains.13 Communication-targeted interventions (eg, communication coaching, question prompt lists, palliative care) are a promising strategy, although existing studies are inconclusive.
The study has limitations. These include relatively low use of the intervention, lack of integration with clinician teaching, and our inability to assess whether expectations for cure reflected knowledge gaps or more subjective factors, such as hope.
In this multicenter randomized clinical trial, provision of a multimedia PC educational intervention did not alter patients’ expectations of cure. Future studies could examine alternative delivery strategies, such as integration with nurse-led teaching, or multipronged interventions combining education with enhanced communication and support.
Accepted for Publication: April 16, 2020.
Corresponding Author: Andrea C. Enzinger, MD, Gastrointestinal Oncology and Palliative Care, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Dana Building, Room 1103, Boston, MA 02215 (firstname.lastname@example.org).
Published Online: July 16, 2020. doi:10.1001/jamaoncol.2020.1921
Author Contributions: Drs Enzinger and Schrag had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Enzinger, McCleary, Bagley, Schrag.
Acquisition, analysis, or interpretation of data: Enzinger, Uno, McCleary, Frank, Sanoff, Van Loon, Matin, Bullock, Cronin, Cibotti, Schrag.
Drafting of the manuscript: Enzinger, Uno, Schrag.
Critical revision of the manuscript for important intellectual content: Enzinger, McCleary, Frank, Sanoff, Van Loon, Matin, Bullock, Cronin, Cibotti, Bagley, Schrag.
Statistical analysis: Enzinger, Uno.
Obtained funding: Enzinger, Schrag.
Administrative, technical, or material support: Enzinger, McCleary, Van Loon, Matin, Bullock, Cronin, Cibotti, Bagley, Schrag.
Study supervision: Enzinger, Van Loon, Bullock, Bagley, Schrag.
Conflict of Interest Disclosures: Dr Sanoff reported grants from Bayer outside the submitted work. Dr Bullock reported grants from Halozyme, Rexahn Pharmaceuticals, Geistlich, AstraZeneca/MedImmune, Agenus, Celgene, Eli Lilly and Company, Klus, and Novocure and personal fees from Eisai and Exelixis outside the submitted work. Dr Schrag reported grants from the Patient-Centered Outcomes Research Institute (PCORI) during the conduct of the study and personal fees from Pfizer and JAMA outside the submitted work. No other disclosures were reported.
Funding/Support: The study was partially funded through PCORI Award CE-1304-6517 (principal investigator, Dr Schrag), National Cancer Institute (NCI) grant K07 CA204201 (principal investigator, Dr Enzinger), and a Junior Investigator Award to Dr Enzinger from the Alliance for Clinical Trials in Oncology NCORP Grant UG1CA189823 (https://acknowledgments.alliancefound.org).
Role of the Funders/Sponsors: PCORI had input into the design and conduct of the study and collection, management, analysis, and interpretation of the data. PCORI had no role in the preparation, review, or approval of the manuscript and decision to submit the manuscript for publication. The NCI had no input into the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review and approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: All statements in this publication, including its findings, are solely those of the authors and do not necessarily represent the views of PCORI, its Board of Governors, or Methodology Committee, or the official views of the National Institutes of Health.
Data Sharing Statement: See Supplement 3.
Additional Contributions: We are grateful to Jennifer Wind, MA, for her expertise in project management and for her assistance throughout the completion of this trial. She was not compensated for this contribution beyond her employment with Dana-Farber Cancer Institute.