Thomas M. Atkinson

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.

Adverse Symptom Event Reporting by Patients vs Clinicians: Relationships With Clinical Outcomes

BACKGROUND In cancer treatment trials, the standard source of adverse symptom data is clinician reporting by use of items from the National Cancer Institutes Common Terminology Criteria for Adverse Events (CTCAE). Patient self-reporting has been proposed as an additional data source, but the implications of such a shift are not understood. METHODS Patients with lung cancer receiving chemotherapy and their clinicians independently reported six CTCAE symptoms and Karnofsky Performance Status longitudinally at sequential office visits. To compare how patients vs clinicians reports relate to sentinel clinical events, a time-dependent Cox regression model was used to measure associations between reaching particular CTCAE grade severity thresholds with the risk of death and emergency room visits. To measure concordance of CTCAE reports with indices of daily health status, Kendall tau rank correlation coefficients were calculated for each symptom with EuroQoL EQ-5D questionnaire and global question scores. Statistical tests were two-sided. RESULTS A total of 163 patients were enrolled for an average of 12 months (range = 1-28 months), with a mean of 11 visits and 67 (41%) deaths. CTCAE reports were submitted by clinicians at 95% of visits and by patients at 80% of visits. Patients generally reported symptoms earlier and more frequently than clinicians. Statistically significant associations with death and emergency room admissions were seen for clinician reports of fatigue (P < .001), nausea (P = .01), constipation (P = .038), and Karnofsky Performance Status (P < .001) but not for patient reports of these items. Higher concordance with EuroQoL EQ-5D questionnaire and global question scores was observed for patient-reported symptoms than for clinician-reported symptoms. CONCLUSIONS Longitudinally collected clinician CTCAE assessments better predict unfavorable clinical events, whereas patient reports better reflect daily health status. These perspectives are complementary, each providing clinically meaningful information. Inclusion of both types of data in treatment trial results and drug labels appears to be warranted.

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.

Cornell Assessment of Pediatric Delirium: A Valid, Rapid, Observational Tool for Screening Delirium in the PICU*

Objective:To determine validity and reliability of the Cornell Assessment of Pediatric Delirium, a rapid observational screening tool. Design:Double-blinded assessments were performed with the Cornell Assessment of Pediatric Delirium completed by nursing staff in the PICU. These ratings were compared with an assessment by consultation liaison child psychiatrist using the Diagnostic and Statistical Manual IV criteria as the “gold standard” for diagnosis of delirium. An initial series of duplicate Cornell Assessment of Pediatric Delirium assessments were performed in blinded fashion to assess interrater reliability. Nurses recorded the time required to complete the Cornell Assessment of Pediatric Delirium screen. Setting:Twenty-bed general PICU in a major urban academic medical center over a 10-week period, March–May 2012. Patients:One hundred eleven patients stratified over ages ranging from 0 to 21 years and across developmental levels. Intervention:Two hundred forty-eight paired assessments completed. Measurements and Main Results:The Cornell Assessment of Pediatric Delirium had an overall sensitivity of 94.1% (95% CI, 83.8–98.8%) and specificity of 79.2% (95% CI, 73.5–84.9%). Overall Cronbach’s &agr; of 0.90 was observed, with a range of 0.87–0.90 for each of the eight items, indicating good internal consistency. A scoring cut point of 9 demonstrated good interrater reliability of the Cornell Assessment of Pediatric Delirium when comparing results of the screen between nurses (overall &kgr; = 0.94; item range &kgr; = 0.68–0.78). In patients without significant developmental delay, sensitivity was 92.0% (95% CI, 85.7–98.3%) and specificity was 86.5% (95% CI, 75.4–97.6%). In developmentally delayed children, the Cornell Assessment of Pediatric Delirium showed decreased specificity of 51.2% (95% CI, 24.7–77.8%) but sensitivity remained high at 96.2% (95% CI, 86.5–100%). The Cornell Assessment of Pediatric Delirium takes less than 2 minutes to complete. Conclusions:With an overall prevalence rate of 20.6% in our study population, delirium is a common problem in pediatric critical care. The Cornell Assessment of Pediatric Delirium is a valid, rapid, observational nursing screen that is urgently needed for the detection of delirium in PICU settings.

Using Confirmatory Factor Analysis to Evaluate Construct Validity of the Brief Pain Inventory (BPI)

CONTEXT The Brief Pain Inventory (BPI) is a frequently used instrument designed to assess the patient-reported outcome of pain. The majority of factor analytic studies have found a two-factor (i.e., pain intensity and pain interference) structure for this instrument; however, because the BPI was developed with an a priori hypothesis of the relationship among its items, it follows that construct validity investigations should use confirmatory factor analysis (CFA). OBJECTIVES The purpose of this work was to establish the construct validity of the BPI using a CFA framework and demonstrate factorial invariance using a range of demographic variables. METHODS A retrospective CFA was completed in a sample of individuals diagnosed with HIV/AIDS and cancer (n=364; 63% male; age 21-92 years, M=51.80). A baseline one-factor model was compared against two-factor and three-factor models (i.e., pain intensity, activity interference, and affective interference) that were developed based on the hypothetical design of the instrument. RESULTS Fit indices for the three-factor model were statistically superior when compared with the one-factor model and marginally better when compared with the two-factor model. This three-factor structure was found to be invariant across disease, age, and ethnicity groups. CONCLUSION The results of this study provide evidence to support a three-factor representation of the BPI, and the originally hypothesized two-factor structure. Such findings will begin to provide clinical trialists, pharmaceutical sponsors, and regulators with confidence in the psychometric properties of this instrument when considering its inclusion in clinical research.

Sports-related and gender differences on neuropsychological measures of frontal lobe functioning.

ObjectiveTo determine similarities and differences in the performance of female and male athletes on neuropsychological measures of frontal lobe functioning. DesignA cross-sectional study of male and female college-aged athletes involved in one of the following sports: hockey, basketball, softball, lacrosse, soccer, swimming, and track. SettingDivision III college. ParticipantsA total of 262 athletes (male, n = 157; female, n = 105) participated in the study. Main Outcome MeasuresControlled Oral Word Association (letters F, A, S), Cognitive Assessment System (Planned Codes, Planned Connections, Number Detection), and WAIS-R-NI Vocabulary were administered to all athletes. ResultsMANCOVA was performed with gender and sport as fixed factors. Female athletes displayed faster and more accurate performance on perceptual-motor tasks (P < 0.01) and on one condition of a verbal fluency task (P < 0.01) compared with male athletes. Male hockey athletes showed superior perceptual-motor speed and accuracy (P < 0.01) compared with male athletes in the track/swimming group. Evaluators were naive to athletes’ gender and sport. ConclusionGender- and sport-specific performances on perceptual-motor and verbal fluency tasks were found. Adding cognitive components to base functions eliminates gender- and sports-related distinctions, suggesting that existing differences are related to basic, fundamental skills, which are inherent and practiced within the respective sport. Understanding the differences and similarities across sports and gender on various neurocognitive measures is relevant for determining group differences in studies examining the consequences of mild traumatic brain injury among athletes.

Psychosocial outcomes and interventions among cancer survivors diagnosed during adolescence and young adulthood (AYA): a systematic review.

PurposeA cancer diagnosis during adolescence or young adulthood (AYA; defined as ages 15–39) generates unique medical and psychosocial needs as developmental milestones are simultaneously impacted. Past research highlights that AYAs’ experiences and psychosocial outcomes are different, and more research and attention is needed. We aimed to identify and synthesize literature regarding psychosocial outcomes, unique needs, and existing psychosocial interventions pertaining to individuals diagnosed with cancer exclusively during AYA, and to highlight areas for future research.MethodsA systematic literature search was conducted using MEDLINE (via PubMed), EMBASE, Cochrane, Web of Science, and PsycINFO (via OVID). Grey literature was searched using key term variations and combinations. Overall, 15,301 records were assessed by two independent reviewers, with 38 studies meeting inclusion criteria.ResultsData synthesis of the 38 articles was organized by four main themes based on quality of life and survivorship: physical well-being (7 studies), psychological well-being (8 studies), social well-being (9 studies), and survivorship care (14 studies). The paucity of studies for such broad inclusion criteria highlights that this population is often combined or subsumed under other age groups, missing needs unique to these AYAs.ConclusionsAYA cancer survivors’ experiences are nuanced, with interacting variables contributing to post-treatment outcomes. AYAs require age-appropriate and flexible care, informational needs and treatment-related education that foster autonomy for long-term survivorship, as well as improved follow-up care and psychological outcomes.Implications for Cancer SurvivorsBy incorporating these findings into practice, the informational and unmet needs of AYAs can be addressed effectively. Education and programming is lacking specific and general subject matter specific to AYAs, incorporating ranging needs at different treatment stages.

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.

Feasibility and clinical impact of sharing patient-reported symptom toxicities and performance status with clinical investigators during a phase 2 cancer treatment trial

Background: Clinicians can miss up to half of patients’ symptomatic toxicities in cancer clinical trials and routine practice. Although patient-reported outcome questionnaires have been developed to capture this information, it is unclear whether clinicians will make use of patient-reported outcomes to inform their own toxicity documentation, or to prompt symptom management activities. Methods: 44 lung cancer patients that participated in a phase 2 treatment trial self-reported 13 symptomatic toxicities derived from the National Cancer Institute’s Common Terminology Criteria for Adverse Events and Karnofsky Performance Status via tablet computers in waiting areas immediately preceding scheduled visits. During visits, clinicians viewed patients’ self-reported toxicity and performance status ratings on a computer interface and could agree or disagree/reassign grades (“shared” reporting). Agreement of clinicians with patient-reported grades was tabulated, and compared using weighted kappa statistics. Clinical actions in response to patient-reported severe (grade 3/4) toxicities were measured (e.g. treatment discontinuation, dose reduction, supportive medications). For comparison, 45 non-trial patients with lung cancer being treated in the same clinic by the same physicians were simultaneously enrolled in a parallel cohort study in which patients also self-reported toxicity grades but reports were not shared with clinicians (“non-shared” reporting). Results: Toxicities and performance status were reported by patients and reviewed by clinicians at (780/782) 99.7% of study visits in the phase 2 trial which used “shared” reporting. Clinicians agreed with patients 93% of the time with kappas 0.82–0.92. Clinical actions were taken in response to 67% of severe patient-reported toxicities. In the “non-shared” reporting comparison group, clinicians agreed with patients 56% of the time with kappas 0.04–0.48 (significantly worse than shared reporting for all symptoms), and clinical actions were taken in response to 44% of severe patient-reported toxicities. Conclusion: Clinicians will frequently agree with patient-reported symptoms and performance status, and will use this information to guide documentation and symptom management. (ClinicalTrials.gov: NCT00807573).

Measurement of Affective and Activity Pain Interference Using the Brief Pain Inventory (BPI): Cancer and Leukemia Group B 70903

OBJECTIVE The Brief Pain Inventory (BPI) was designed to yield separate scores for pain intensity and interference. It has been proposed that the pain interference factor can be further broken down into unique factors of affective (e.g., mood) and activity (e.g., work) interference. The purpose of this analysis was to confirm this affective/activity interference dichotomy. PATIENTS AND METHODS A retrospective confirmatory factor analysis was completed for a sample of 184 individuals diagnosed with castrate-resistant prostate cancer (age 40-86, mean = 65.46, 77% White non-Hispanic) who had been administered the BPI as part of Cancer and Leukemia Group B trial 9480. A one-factor model was compared against two-factor and three-factor models that were developed based on the design of the instrument. RESULTS Root mean squared error of approximation (0.075), comparative fit index (0.971), and change in chi-square, given the corresponding change in degrees of freedom (13.33, P < 0.05) values for the three-factor model (i.e., pain intensity, activity interference, and affective interference), were statistically superior in comparison with the one- and two-factor models. This three-factor structure was found to be invariant across age, mean prostate-specific antigen, and hemoglobin levels. CONCLUSIONS These results confirm that the BPI can be used to quantify the degree to which pain separately interferes with affective and activity aspects of a patients everyday life. These findings will provide clinical trialists, pharmaceutical sponsors, and regulators with confidence in the flexibility of the BPI as they consider the use of this instrument to assist with understanding the patient experience as it relates to treatment.