Patient free text reporting of symptomatic adverse events in cancer clinical research using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Objective: The study sought to describe patient-entered supplemental information on symptomatic adverse events (AEs) in cancer clinical research reported via a National Cancer Institute software system and examine the feasibility of mapping these entries to established terminologies. Materials and Methods: Patients in 3 multicenter trials electronically completed surveys during cancer treatment. Each survey included a prespecified subset of items from the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Upon completion of the survey items, patients could add supplemental symptomatic AE information in a free text box. As patients typed into the box, structured dropdown terms could be selected from the PRO-CTCAE item library or Medical Dictionary for Regulatory Activities (MedDRA), or patients could type unstructured free text for submission. Results: Data were pooled from 1760 participants (48% women; 78% White) who completed 8892 surveys, of which 2387 (26.8%) included supplemental symptomatic AE information. Overall, 1024 (58%) patients entered supplemental information at least once, with an average of 2.3 per patient per study. This encompassed 1474 of 8892 (16.6%) dropdowns and 913 of 8892 (10.3%) unstructured free text entries. One-third of the unstructured free text entries (32%) could be mapped post hoc to a PRO-CTCAE term and 68% to a MedDRA term. Discussion: Participants frequently added supplemental information beyond study-specific survey items. Almost half selected a structured dropdown term, although many opted to submit unstructured free text entries. Most free text entries could be mapped post hoc to PRO-CTCAE or MedDRA terms, suggesting opportunities to enhance the system to perform real-time mapping for AE reporting. Conclusions: Patient reporting of symptomatic AEs using a text box functionality with mapping to existing terminologies is both feasible and informative

Methods for Implementing and Reporting Patient-reported Outcome (PRO) Measures of Symptomatic Adverse Events in Cancer Clinical Trials

Purpose There is increasing interest to use patient-reported outcome (PRO) measures to evaluate symptomatic adverse events (AEs) in cancer treatment trials. However, there are currently no standard recommended approaches for integrating patient-reported AE measures into trials. Methods Approaches are identified from previous trials for selecting AEs for solicited patient reporting, administering patient-reported AE measures, and analyzing and reporting results. Findings Approaches for integrating patient-reported AE measures into cancer trials generally combine current standard methods for clinician-reported AEs and established best practices for using PRO measures. Specific AEs can be selected for a PRO questionnaire based on common and expected reactions in a given trial context, derived from literature review and qualitative/mixed-methods evaluations and should be the same set administered across all arms of a trial. A mechanism for collecting unsolicited patient-reported AEs will also ideally be included. Patients will preferably report at baseline and at the end of active treatment as well as on a frequent standardized schedule during active treatment, such as weekly from home, with a recall period corresponding to the frequency of reporting (eg, past 7 days). Less frequent reporting may be considered after an initial intensive monitoring period for trials of prolonged treatments and during long-term follow-up. Electronic PRO data collection is preferred. Backup data collection for missed PRO reports is advisable to boost response rates. Analysis can use a combination of approaches to AE and PRO data. If a high proportion of patients is experiencing baseline symptoms, systematic subtraction of these from on-study AEs should be considered to improve reporting of symptoms related to treatment. More granular longitudinal analyses of individual symptoms can also be useful. Implications Methods are evolving for integrating patient-reported symptomatic AEs into cancer trials. These methods are expected to further evolve as more data from trials become available

Software for administering the National Cancer Institute’s patient-reported outcomes version of the common terminology criteria for adverse events: Usability study

Background: The US National Cancer Institute (NCI) developed software to gather symptomatic adverse events directly from patients participating in clinical trials. The software administers surveys to patients using items from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) through Web-based or automated telephone interfaces and facilitates the management of survey administration and the resultant data by professionals (clinicians and research associates). Objective: The purpose of this study was to iteratively evaluate and improve the usability of the PRO-CTCAE software. Methods: Heuristic evaluation of the software functionality was followed by semiscripted, think-aloud protocols in two consecutive rounds of usability testing among patients with cancer, clinicians, and research associates at 3 cancer centers. We conducted testing with patients both in clinics and at home (remotely) for both Web-based and telephone interfaces. Furthermore, we refined the software between rounds and retested. Results: Heuristic evaluation identified deviations from the best practices across 10 standardized categories, which informed initial software improvement. Subsequently, we conducted user-based testing among 169 patients and 47 professionals. Software modifications between rounds addressed identified issues, including difficulty using radio buttons, absence of survey progress indicators, and login problems (for patients) as well as scheduling of patient surveys (for professionals). The initial System Usability Scale (SUS) score for the patient Web-based interface was 86 and 82 (P=.22) before and after modifications, respectively, whereas the task completion score was 4.47, which improved to 4.58 (P=.39) after modifications. Following modifications for professional users, the SUS scores improved from 71 to 75 (P=.47), and the mean task performance improved significantly (4.40 vs 4.02; P=.001). Conclusions: Software modifications, informed by rigorous assessment, rendered a usable system, which is currently used in multiple NCI-sponsored multicenter cancer clinical trials

The Contribution of Patient Reported Outcome Measures to Shared Decision-Making in Radiation Oncology at a Midwestern Comprehensive Cancer Center

Background. Chronic diseases, such as lung cancer, require a provider-patient relationship developed over time. This relationship fosters shared decision-making (SDM), a collaborative, dynamic information exchange and analysis between provider and patient regarding treatment and desired outcomes. Established benefits to SDM include an improved quality of life and decreased anxiety and depression. Despite established benefits, recent research suggests radiation oncologists are not engaging in SDM. A decision-aid tool utilizing patient reported outcome measures may increase SDM between radiation oncologists and patients with lung cancer. Patient-reported outcome measures, wherein the patient provides direct assessment of their health and quality of life, can inform and initiate SDM. This study investigated the design and implementation of a collaborative decision-aid tool for patients with lung cancer at a Midwestern cancer center as informed by stakeholders, practice considerations, and the evidence base. Objectives. The primary objective was to develop a collaborative decision-aid tool, using patient-reported outcome measures, that can be implemented in an academic radiation oncology clinic. Secondary objectives then assessed the tool’s impact through surrogates of shared decision making (add-on oncology visits, concomitant medication prescriptions), medical management (adverse events, radiation therapy compliance, chemotherapy compliance) and emergent care and its costs (emergency room visits and estimated costs, inpatient admissions and estimated costs). The hypothesized result was a decision aid designed to increase collaborative communication between radiation oncologists and patients will result in improved shared decision making, yielding better medical management and patient outcomes and reducing emergent care costs. Lastly, an implementation roadmap provided information on experienced barriers, facilitators, and considerations for performance objectives. Materials and Methods. A sequential exploratory mixed methods design was employed. The qualitative strand explored how stakeholders, practice considerations, and the evidence base informed the design and installation of an ideal collaborative decision-aid tool. Semi-structured interviews were completed with both patients who completed radiation therapy for lung cancer and their radiation oncologist. Interviews were coded and evaluated for themes. Interviews were transcribed verbatim, coded using Atlas.ti software, and analyzed thematically and visually. The results of this analysis, combined with information from the literature base and implementation stakeholders, was used to inform design of the collaborative decision-aid tool that was installed employing the principles of clinical implementation using the plan-do-study-act (PDSA) implementation cycle model. Simple descriptive analysis was performed on objective measures. Mixed analysis included data display, comparison, and integration. Results. Six patients and six radiation oncologists participated in the semi-structured interviews. Interviews provided insights that patients did not know what to ask of their radiation oncologists, prioritized survival over reduced side effects, and minimized complaints to their radiation oncologists, often to their detriment. Interviews yielded feedback on commonly used patient reported outcome instruments, identifying context as important and the recall timeframe as difficult. Commonly patient-identified adverse events of concern were fatigue, dyspnea, vomiting, and dysphagia. Radiation oncologists identified a patient’s personality as critical to care and translating responses and symptoms to adverse events of treatment. For this reason, numeric scales were not endorsed as they were seen as ambiguous and lacking context. With this feedback, a collaborative decision-aid tool was designed that focused on adverse events of interest (nausea, vomiting, fatigue, dyspnea, chest pain, weight loss). Rather than numeric scales, responses provided granular context that clued physicians to medical needs (i.e., “I cannot walk to my appointment,” “It hurts when I eat,” “I am not vomiting but I’m not hungry”). This tool was implemented as a quality initiative project for pragmatic impact. Four patients were assigned the tool during the first PDSA implementation cycle. The first follow-up evaluation meeting identified four critical outcomes for the next implementation cycle: how to identify which consults require the decision-aid, how the need for the decision-aid on doctor visits is consistently provided to scheduling, how unplanned visits/special complaints are addressed with regard to the decision-aid, and what actions are necessary if the patient leaves prior to the decision-aid being reviewed. Mixed analysis provided direction for next steps in implementation, tool design, and quantitative data measures. The primary concern, increase in time expended per clinic visit, was not supported by the limited data available from the first implementation cycle. Conclusion. Implementation of collaborative decision-aid within the radiation oncology clinic is feasible without disruption of the on-treatment visit time. Radiation oncologists can use the tool as a guide for routine on-treatment visit review, so that it is harmonized with their routine practice. Care should be taken during implementation to ensure all stakeholders are included in the tool’s implementation and that desired outcomes are appropriately identified to truly capture what impact the tool has, if any, on clinical outcomes. Focusing on the patient with the goal of improving their experience will guide collaborative decision-aid tool adaptation, implementation, and uptake

Stakeholder perspectives on addressing adverse events from adjuvant cancer therapy: A qualitative study

Background: With increasing survival rates, a growing population of patients with cancer have received or will receive adjuvant therapy to prevent cancer recurrences. Patients and caregivers will confront the complexities of balancing the preventative benefits of adjuvant therapy with possible near-term or long-term adverse events (AEs). Adjuvant treatment–related AEs (from minimal to severe) can impact therapeutic adherence, quality of life, emotional and physical health, and survival. However, to the authors' knowledge, limited information is available regarding how stakeholders use or desire to use adjuvant-related AE information to inform the care of patients with cancer. Methods: A qualitative, purposeful sampling approach was used to elicit stakeholder feedback via semistructured interviews (24 interviews). Drug development, drug regulatory, clinical, payer, and patient/patient advocacy stakeholders were questioned about the generation, dissemination, and use of adjuvant treatment–related AE information to inform the care of patients with cancer. Transcripts were coded independently by 2 senior health care researchers and reconciled to identify key themes. Results: All stakeholder groups in the current study identified needed improvements in each of the following 4 areas: 1) improving the accessibility and relevance of AE-related information; 2) better integrating and implementing available information regarding AEs for decisions; 3) connecting contemporary cultural and economic value systems to the generation and use of information regarding adjuvant treatment–related AEs; and 4) addressing a lack of alignment and ownership of stakeholder efforts to improve the use of AE information in the adjuvant setting. Conclusions: Despite commonalities in the overall needs identified by the diverse stakeholders in the current study, broad systemic change has been stymied. The current study identified the lack of alignment and the absence of a central “owner” of these diffuse efforts as a previously unrecognized hurdle to realizing the desired systemic improvements. Future initiatives aimed at improving quality of life and outcomes for patients receiving adjuvant therapy through the improved use of AE information must address this challenge through innovative collectives and novel leadership strategies

Population-level evidence of survival benefits of patient-reported outcome symptom monitoring software systems in routine cancer care

Symptom management is a cornerstone of quality oncology care. Most patients with cancer experience debilitating symptoms related to the disease itself or to treatment toxicities. If symptoms are not detected early enough, they can worsen and lead to unnecessary suffering, avoidable hospital services, and even death. Numerous prior studies have shown that up to half of patients' symptoms go undetected by their care teams. There is therefore a substantial opportunity to improve symptom detection and early interventions to avoid downstream complications and improve outcomes

Feasibility of a Text Messaging-Integrated and Chatbot-Interfaced Self-Management Program for Symptom Control in Patients With Gastrointestinal Cancer Undergoing Chemotherapy: Pilot Mixed Methods Study

BACKGROUND: Outpatient chemotherapy often leaves patients to grapple with a range of complex side effects at home. Leveraging tailored evidence-based content to monitor and manage these symptoms remains an untapped potential among patients with gastrointestinal (GI) cancer. OBJECTIVE: This study aims to bridge the gap in outpatient chemotherapy care by integrating a cutting-edge text messaging system with a chatbot interface. This approach seeks to enable real-time monitoring and proactive management of side effects in patients with GI cancer undergoing intravenous chemotherapy. METHODS: Real-Time Chemotherapy-Associated Side Effects Monitoring Supportive System (RT-CAMSS) was developed iteratively, incorporating patient-centered inputs and evidence-based information. It synthesizes chemotherapy knowledge, self-care symptom management skills, emotional support, and healthy lifestyle recommendations. In a single-arm 2-month pilot study, patients with GI cancer undergoing chemotherapy received tailored intervention messages thrice a week and a weekly Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events-based symptom assessment via a chatbot interface. Baseline and postintervention patient surveys and interviews were conducted. RESULTS: Out of 45 eligible patients, 34 were enrolled (76% consent rate). The mean age was 61 (SD 12) years, with 19 (56%) being females and 21 (62%) non-Hispanic White. The most common cancer type was pancreatic (n=18, 53%), followed by colon (n=12, 35%) and stomach (n=4, 12%). In total, 27 (79% retention rate) participants completed the postintervention follow-up. In total, 20 patients texted back at least once to seek additional information, with the keyword chemo or support texted the most. Among those who used the chatbot system checker, fatigue emerged as the most frequently reported symptom (n=15), followed by neuropathy (n=7). Adjusted for multiple comparisons, patients engaging with the platform exhibited significantly improved Patient Activation Measure (3.70, 95% CI -6.919 to -0.499; P=.02). Postintervention interviews and satisfaction surveys revealed that participants found the intervention was user-friendly and were provided with valuable information. CONCLUSIONS: Capitalizing on mobile technology communication holds tremendous scalability for enhancing health care services. This study presents initial evidence of the engagement and acceptability of RT-CAMSS, warranting further evaluation in a controlled clinical trial setting

Biobehavioral influences of chemotherapy-induced mucositis in adolescents and young adults with cancer

Cancer-directed therapies are inherently toxic and their use requires a fine balance between administering chemotherapy that is aggressive and potent enough to kill the neoplastic tissues, but not to cause undue permanent harm to the patient. Mucositis is one of these toxicities, and one of the most burdensome and distressing adverse effects of therapy. The condition is acutely painful, introduces risk for life-threatening infections, and significantly contributes to the financial burden of cancer therapy. Importantly, it is a dose-limiting toxicity, so when it presents to severe degrees, therapy intensity must be de-escalated to allow for healing and to prevent subsequent development; a solitary incidence can change the trajectory of therapy for a patient, compromising the ability to deliver intensive therapy and reducing the chance of survival. The pathobiology of mucositis is not well-understood, but cross-sectional and in-vitro studies suggest that the patient’s inflammatory response perpetuates and exacerbates development and animal models suggest that stress predicts development via stress-induced inflammation, but this has not been well explored in humans. Adolescents and young adults with cancer have the highest rates of dose-limiting mucositis and the highest reported stress while undergoing therapy, suggesting that findings from animal models hold true in humans. These relationships have not yet been explored in the clinical setting, but an improved understanding would identify if stress and inflammation are risk factors for mucositis and warrant intervention to prevent toxicity development. This study employs a prospective design to assess if stress and inflammation at the time of chemotherapy administration in adolescent and young adults predicts mucositis development. Thirty adolescents and young adults receiving chemotherapy with a significant chance of inducing mucositis completed baseline stress questionnaire and had inflammatory markers evaluated via blood the morning they received chemotherapy. For the following fourteen days, participants reported intensity of mucositis symptoms. Regression analyses evaluated if baseline stress or inflammation predicted mucositis and tests of mediation assessed if inflammation mediated the relationship between stress and mucositis. When controlling for relevant confounding variables, stress emerged as a significant predictor for peak mucositis intensity (=0.052, p=0.018) and predicted total mucositis score (=0.281, p=0.023), but did not reliably predict mucositis incidence (OR = 1.13, p=0.125). Multiple inflammatory biomarkers were analyzed and IL-1a was predictive of mucositis incidence (OR = 2.66, p=0.084), but this was only significant at the =0.1 level. Epidermal growth factor predicted peak severity (B=-0.004, p=0.025) and total score (B=-0.024, p=0.030). Mediation analysis suggests that epidermal growth factor, IL8, and vascular endothelial growth factor mediate 1.4-8.1% of the effect that stress has on mucositis. While these effect sizes are small, these data suggest that baseline stress and inflammatory profiles influence mucositis development. Additional research is needed to better elucidate and quantify these relationships in larger, more robustly powered studies that can control for additional clinical factors. However, since stress and inflammation are modifiable factors, they hold promise as targets for interventions to prevent mucositis development