Antonia V. Bennett

Symptom Monitoring With Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial

PURPOSE There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, but evidence of impact on clinical outcomes is limited. METHODS We randomly assigned patients receiving routine outpatient chemotherapy for advanced solid tumors at Memorial Sloan Kettering Cancer Center to report 12 common symptoms via tablet computers or to receive usual care consisting of symptom monitoring at the discretion of clinicians. Those with home computers received weekly e-mail prompts to report between visits. Treating physicians received symptom printouts at visits, and nurses received e-mail alerts when participants reported severe or worsening symptoms. The primary outcome was change in health-related quality of life (HRQL) at 6 months compared with baseline, measured by the EuroQol EQ-5D Index. Secondary endpoints included emergency room (ER) visits, hospitalizations, and survival. RESULTS Among 766 patients allocated, HRQL improved among more participants in the intervention group than usual care (34% v 18%) and worsened among fewer (38% v 53%; P < .001). Overall, mean HRQL declined by less in the intervention group than usual care (1.4- v 7.1-point drop; P < .001). Patients receiving intervention were less frequently admitted to the ER (34% v 41%; P = .02) or hospitalized (45% v 49%; P = .08) and remained on chemotherapy longer (mean, 8.2 v 6.3 months; P = .002). Although 75% of the intervention group was alive at 1 year, 69% with usual care survived the year (P = .05), with differences also seen in quality-adjusted survival (mean of 8.7 v. 8.0 months; P = .004). Benefits were greater for participants lacking prior computer experience. Most patients receiving intervention (63%) reported severe symptoms during the study. Nurses frequently initiated clinical actions in response to e-mail alerts. CONCLUSION Clinical benefits were associated with symptom self-reporting during cancer care.

Development of the National Cancer Institute’s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

The standard approach for documenting symptomatic adverse events (AEs) in cancer clinical trials involves investigator reporting using the National Cancer Institutes (NCIs) Common Terminology Criteria for Adverse Events (CTCAE). Because this approach underdetects symptomatic AEs, the NCI issued two contracts to create a patient-reported outcome (PRO) measurement system as a companion to the CTCAE, called the PRO-CTCAE. This Commentary describes development of the PRO-CTCAE by a group of multidisciplinary investigators and patient representatives and provides an overview of qualitative and quantitative studies of its measurement properties. A systematic evaluation of all 790 AEs listed in the CTCAE identified 78 appropriate for patient self-reporting. For each of these, a PRO-CTCAE plain language term in English and one to three items characterizing the frequency, severity, and/or activity interference of the AE were created, rendering a library of 124 PRO-CTCAE items. These items were refined in a cognitive interviewing study among patients on active cancer treatment with diverse educational, racial, and geographic backgrounds. Favorable measurement properties of the items, including construct validity, reliability, responsiveness, and between-mode equivalence, were determined prospectively in a demographically diverse population of patients receiving treatments for many different tumor types. A software platform was built to administer PRO-CTCAE items to clinical trial participants via the internet or telephone interactive voice response and was refined through usability testing. Work is ongoing to translate the PRO-CTCAE into multiple languages and to determine the optimal approach for integrating the PRO-CTCAE into clinical trial workflow and AE analyses. It is envisioned that the PRO-CTCAE will enhance the precision and patient-centeredness of adverse event reporting in cancer clinical research.

Electronic patient-reported outcome systems in oncology clinical practice.

Answer questions and earn CME/CNE

Feasibility of Long-Term Patient Self-Reporting of Toxicities From Home via the Internet During Routine Chemotherapy

PURPOSE Patient-reported outcomes are increasingly used in routine outpatient cancer care to guide clinical decisions and enhance communication. Prior evidence suggests good patient compliance with reporting at scheduled clinic visits, but there is limited evidence about compliance with long-term longitudinal reporting between visits. PATIENTS AND METHODS Patients receiving chemotherapy for lung, gynecologic, genitourinary, or breast cancer at a tertiary cancer center, with access to a home computer and prior e-mail experience, were asked to self-report seven symptomatic toxicities via the Web between visits. E-mail reminders were sent to participants weekly; patient-reported high-grade toxicities triggered e-mail alerts to nurses; printed reports were provided to oncologists at visits. A priori threshold criteria were set to determine if this data collection approach merited further development based on monthly (≥ 75% participants reporting at least once per month on average) and weekly compliance rates (60% at least once per week). RESULTS Between September 2006 and November 2010, 286 patients were enrolled (64% were women; 88% were white; median age, 58 years). Mean follow-up was 34 weeks (range, 2 to 214). On average, monthly compliance was 83%, and weekly compliance was 62%, without attrition until the month before death. Greater compliance was associated with older age and higher education but not with performance status. Compliance was greatest during the initial 12 weeks. Symptomatic illness and technical problems were rarely barriers to compliance. CONCLUSION Monthly compliance with home Web reporting was high, but weekly compliance was lower, warranting strategies to enhance compliance in routine care settings.

Use of Patient-Reported Outcomes to Improve the Predictive Accuracy of Clinician-Reported Adverse Events

Abundant research has now demonstrated that patient and clinician reports of symptoms—and particularly symptomatic toxicities (ie, adverse events) during cancer treatment—provide discrepant yet complementary data (1–3). How can this be? Can’t only the patient or the clinician be “right”? The more patient-centered among us might state that the patient is always right by definition because nobody (not even the most sensitive clinician) can truly know another person’s subjective experience. But the more traditional among us might assert that clinicians should be considered right because they have an “objective” perspective based on experience and training, which prevents them from exaggerating or understating what they observe. In fact, it appears that both the patient and clinician provide information of value, which when combined provides a more accurate understanding of the patient’s symptoms. This finding is good news for those of us who are interested in improving the measurement of symptoms in clinical trials and practice. The optimistic among us might state that all we need to do now is figure out how to operationalize this approach.

Impact of Erythropoiesis-Stimulating Agents on Energy and Physical Function in Nondialysis CKD Patients With Anemia: A Systematic Review

BACKGROUND Previous analyses report the impact of erythropoiesis-stimulating agents (ESAs) on health-related quality of life across various populations. In this analysis, we review published studies and quantify the effect of ESA therapy on energy/fatigue and physical function in nondialysis patients with chronic kidney disease (CKD) related anemia. STUDY DESIGN Systematic literature search to identify articles (1980-2008) that evaluated effects of ESAs on patient-reported energy and physical function. SETTING & POPULATION Nondialysis CKD patients with anemia enrolled in prospective trials. SELECTION CRITERIA FOR STUDIES Prospective studies measuring energy or physical function with both baseline and follow-up measurement. INTERVENTION ESA treatment. OUTCOMES Improvements in energy and physical function assessed using effect size, a measure of treatment responsiveness. RESULTS 14 studies were identified: 11 measured energy and 14 measured physical function. The 36-Item Short-Form Health Survey (SF-36) was the most common instrument used to report energy and physical function. Of 11 studies measuring energy, 2 were double-blind randomized placebo-controlled trials (RCTs), 5 were open-label RCTs, and 4 were single-arm open-label studies. Eight of 11 studies reported statistically significant improvements in energy. Effect size for energy ranged from small (0.24) to large (1.90) in ESA-treated groups and was moderate in each arm of the low- versus high-hemoglobin target RCTs. Of 14 studies measuring physical function, 2 were double-blind RCTs, 6 were open-label RCTs, and 6 were single-arm open-label studies. Ten of 14 studies reported statistically significant improvements in physical function. Effect size for physical function ranged from small (0.37) to large (2.38) in ESA-treated groups and was negligible to moderate in each arm of low- versus high-hemoglobin target studies. LIMITATIONS Findings and conclusions were limited by the available evidence. CONCLUSION RCTs and single-arm studies indicate that treatment of anemia with ESAs improves energy and physical function in nondialysis CKD patients.

Sexual Functioning Among Endometrial Cancer Patients Treated With Adjuvant High-Dose-Rate Intra-Vaginal Radiation Therapy

PURPOSE We used the Female Sexual Function Index (FSFI) to investigate the prevalence of sexual dysfunction (SD) and factors associated with diminished sexual functioning in early stage endometrial cancer (EC) patients treated with simple hysterectomy and adjuvant brachytherapy. METHODS AND MATERIALS A cohort of 104 patients followed in a radiation oncology clinic completed questionnaires to quantify current levels of sexual functioning. The time interval between hysterectomy and questionnaire completion ranged from <6 months to >5 years. Multivariate regression was performed using the FSFI as a continuous variable (score range, 1.2-35.4). SD was defined as an FSFI score of <26, based on the published validation study. RESULTS SD was reported by 81% of respondents. The mean (± standard deviation) domain scores in order of highest-to-lowest functioning were: satisfaction, 2.9 (± 2.0); orgasm, 2.5 (± 2.4); desire, 2.4 (± 1.3); arousal, 2.2 (± 2.0); dryness, 2.1 (± 2.1); and pain, 1.9 (± 2.3). Compared to the index population in which the FSFI cut-score was validated (healthy women ages 18-74), all scores were low. Compared to published scores of a postmenopausal population, scores were not statistically different. Multivariate analysis isolated factors associated with lower FSFI scores, including having laparotomy as opposed to minimally invasive surgery (effect size, -7.1 points; 95% CI, -11.2 to -3.1; P<.001), lack of vaginal lubricant use (effect size, -4.4 points; 95% CI, -8.7 to -0.2, P=.040), and short time interval (<6 months) from hysterectomy to questionnaire completion (effect size, -4.6 points; 95% CI, -9.3-0.2; P=.059). CONCLUSIONS The rate of SD, as defined by an FSFI score <26, was prevalent. The postmenopausal status of EC patients alone is a known risk factor for SD. Additional factors associated with poor sexual functioning following treatment for EC included receipt of laparotomy and lack of vaginal lubricant use.

Emerging uses of patient generated health data in clinical research.

Recent advancements in consumer directed personal computing technology have led to the generation of biomedically‐relevant data streams with potential health applications. This has catalyzed international interest in Patient Generated Health Data (PGHD), defined as “health‐related data – including health history, symptoms, biometric data, treatment history, lifestyle choices, and other information‐created, recorded, gathered, or inferred by or from patients or their designees (i.e. care partners or those who assist them) to help address a health concern.”(Shapiro et al., 2012) PGHD offers several opportunities to improve the efficiency and output of clinical trials, particularly within oncology. These range from using PGHD to understand mechanisms of action of therapeutic strategies, to understanding and predicting treatment‐related toxicity, to designing interventions to improve adherence and clinical outcomes. To facilitate the optimal use of PGHD, methodological research around considerations related to feasibility, validation, measure selection, and modeling of PGHD streams is needed. With successful integration, PGHD can catalyze the application of “big data” to cancer clinical research, creating both “n of 1” and population‐level observations, and generating new insights into the nature of health and disease.

Patient-Reported Outcomes in Clinical Trials of Rare Diseases

ABSTRACTThe science of measuring patient-reported outcomes (PROs) has advanced substantially in recent decades, allowing evaluation of how patients feel and function in clinical research. Assessment of the patient experience in populations with rare diseases can be successfully achieved using PRO measures when careful planning and rigorous methods are employed. A number of challenges exist when designing and implementing PRO analyses in rare disease contexts, including heterogeneity of outcomes, availability of suitable measures, recruitment, and selection of appropriate data collection methods. Strategies to address these exist and have been employed in past clinical research, particularly in pediatric populations. PRO assessments in rare disease clinical trials have been particularly successful through partnerships between investigators, PRO methodologists, and patient organizations. The overall goal of PRO measurement is to understand the patient experience and it provides an essential part of evaluating the impact of disease and treatment.

Comparison of 7-day recall and daily diary reports of COPD symptoms and impacts.

OBJECTIVE Patient reporting of symptoms in a questionnaire with a 7-day recall period was expected to differ from symptom reporting in a 7-day symptom diary on the basis of cognitive theory of memory processes and several studies of symptoms and health behaviors. METHODS A total of 101 adults with chronic obstructive pulmonary disease (COPD) completed a daily diary of items measuring symptoms and impacts of COPD for 7 days, and on the seventh day they completed a questionnaire of the same items with a 7-day recall period. The analysis examined concordance of 7-day recall with summary descriptors of the daily responses, examined the magnitude and covariates (patient characteristics and response patterns) of the difference between 7-day recall and mean of daily responses, and compared the discriminant ability and ability to detect change of 7-day recall and mean of daily responses. RESULTS A 7-day recall was moderately concordant with the mean and maximum of daily responses and was 0.34 to 0.50 SDs higher than the mean of daily responses. Only the weekly report itself was a covariate of the difference. The discriminant ability and ability to detect change were equivalent. CONCLUSIONS In measuring the weeklong experience of COPD symptoms and impacts on groups of patients, the 7-day recall scores were higher than the daily diary scores, but equivalent in detecting change over time.