Patient-Reported Outcomes in Clinical Trials of Rare Diseases

The 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

Symptom burden and life challenges reported by adult chordoma patients and their caregivers

PURPOSE: This study aims to characterize the symptom burden and life challenges that chordoma patients and their caregivers experience. METHODS: In this cross-sectional study, we analyzed data from the Chordoma Foundation online community survey conducted in 2014. Frequency counts and percentages were calculated to determine the prevalence of self-reported symptoms and life challenges in the sample. We used Fisher's exact test to compare self-reported symptoms among subgroups with different disease status, tumor locations, and treatments received. RESULTS: Among the survey participants, 358 identified themselves as chordoma patients and 208 as caregivers. The majority of the patients were over 45 years (72%), male (56%), educated beyond high school degree (87%), and from North America (77%). Skull base was the most prevalent tumor location (40%). Chronic pain (38%) was the most commonly reported symptom followed by depression or severe anxiety (35%), and chronic fatigue (34%). Among patients, the most commonly-reported challenges included delayed diagnosis (37%), long-term disability (33%), and change in career or reduced ability to work (33%). For caregivers, grief (55%), delayed diagnosis (47%), and difficulty helping the patient cope with his or her disease (45%) were most common. CONCLUSIONS: Our study findings suggest a high symptom burden and life challenges among chordoma patients and their caregivers. This study provides preliminary, limited estimates of the prevalence of a wide range of self-reported symptoms and challenges that will inform the assessment of patient-reported outcomes in future clinical trials and help clinicians better manage chordoma patients' symptoms

A systematic review of patient reported outcomes in phase II or III clinical trials of myelodysplastic syndromes and acute myeloid leukemia

The purpose of this systematic literature review was to identify clinical trials of MDS and AML that included patient-reported outcome (PRO) instruments, and to summarize the symptom and other health related quality of life (HRQOL) concepts most frequently assessed and the PRO instruments that were used. Sixteen manuscripts describing 14 distinct trials met all criteria (i.e., phase 2 or 3 clinical trial for MDS or AML which included PRO assessment) and were published between 1996-2017. In trials evaluating anemia, PRO scores showed significant improvement in relevant domains (e.g. fatigue, function) among patients identified as responders. In trials evaluating the impact of anti-cancer therapies, improvements the baseline to end of treatment were observed in physical functioning and HRQOL, however the rates of missing data in many of the trials was high or unreported. PRO instruments have the ability to capture changes over time in patients’ function and well-being, and PRO instruments and guidance documents are available to support the assessment of HRQOL in AML/MDS clinical trials

Psychometric properties of the FACT-G quality of life scale for family caregivers of cancer patients

Purpose This study aimed to examine psychometric properties of a caregiver version of the well-established Functional Assessment of Cancer Therapy-General Scale (FACT-G) after conducting focus groups and obtaining expert input. Methods We made minor wording modifications to the Patient FACT-G to enable caregivers to report how the illness affected their overall quality of life (QOL) and well-being on four subscales (physical, social, emotional, functional). We tested the acceptability, precision, factor structure, reliability and validity of the Caregiver FACT-G among partners of prostate cancer patients (N = 263) and caregivers (spouses, siblings, adult children) of patients with advanced cancer (breast, lung, colorectal, prostate) (N = 484) using data from two Randomized Clinical Trials (RCTs). Results With a factor structure similar to the Patient FACT-G, Caregiver FACT-G was acceptable and precise in measuring caregiver QOL, with high inter-factor correlations and internal consistency reliability (Cronbach’s alphas 0.81–0.91). The Caregiver FACT-G had strong convergent validity demonstrated by significant positive correlations with caregiver self-efficacy (0.25–0.63), dyadic communication (0.18–0.51), and social support (0.18–0.54) in both samples. It also had strong discriminant validity evidenced by significant inverse correlations with negative appraisal of caregiving (− 0.37 to − 0.69), uncertainty (− 0.28 to − 0.53), hopelessness (− 0.25 to − 0.60), and avoidant coping (− 0.26 to − 0.58) in both samples. Caregivers’ baseline FACT-G scores were significantly associated with their physical (0.23) and mental well-being (0.54; 4-month follow-up) and their depression (− 0.69; 3-month follow-up), indicating strong predictive validity. Conclusion This is the first study evaluating the psychometric properties of the Caregiver FACT-G. More psychometric testing is warranted, especially among caregivers of diverse sociocultural backgrounds

Evaluation of mode equivalence of the MSKCC Bowel Function Instrument, LASA Quality of Life, and Subjective Significance Questionnaire items administered by Web, interactive voice response system (IVRS), and paper

To assess the equivalence of patient-reported outcome (PRO) survey responses across Web, interactive voice response system (IVRS), and paper modes of administration

Prevalence of patientreported gastrointestinal symptoms and agreement with clinician toxicity assessments in radiation therapy for anal cancer.

Purpose Gastrointestinal (GI) symptoms pose a significant burden to patients receiving chemoradiation therapy (CRT) for anal cancer; however, the impact of symptoms from the patient perspective has not been quantified. This retrospective study examined and compared patient and clinician reports of acute GI toxicity during CRT. Materials and methods Patients treated with definitive RT using intensity-modulated radiation therapy for anal cancer between 9/09 and 11/12 were reviewed. Median RT dose was 56 Gy (range 45–56), and 76 patients (97%) received concurrent 5-fluorouracil-based chemotherapy. During RT, patients completed the 7-item Bowel Problem Scale (BPS) weekly. Clinicians assessed toxicity separately using CTCAE v. 3.0. Scores of BPS C 3 and CTCAE C 1 were considered to be clinically meaningful. Agreement of the two assessments was evaluated by Cohen’s kappa coefficient. Results Seventy-eight patients completed at least one BPS and had a corresponding clinician assessment. Patients reporting scores of C3 was highest at week 5 (n = 68) for diarrhea (44.1%), proctitis (57.4%), and mucus (48.4%), while urgency (47.6%), tenesmus (31.7%), and cramping (27%) were highest at week 4 (n = 63). Baseline bleeding scores (26.7%; score C3) improved during treatment (13.4% at week 5). ‘‘Poor’’ agreement was observed between patient- and clinician-reported proctitis (Cohen’s k = 0.11; n = 58); however, there was ‘‘good’’ agreement for diarrhea (Cohen’s k = 0.68; n = 58). Conclusions Acute GI toxicity during definitive CRT for anal cancer was most significant during weeks 4–5, while rectal bleeding improved during treatment. Discrepancies in patient- and clinician-reported symptoms demonstrate the potential for patient-reported outcomes to be useful tools for anal cancer clinical assessments

A Library of Instruments Endorsed by Published Systematic Reviews for Assessing Patients and Their Care Developed by the Palliative Care Research Cooperative

Dear Editor: Palliative care research encompasses a broad array of domains, care settings, and illnesses, and the instrument literature can be difficult and time consuming to navigate. The Palliative Care Research Cooperative (PCRC) has compiled a library of *150 instruments for assessing patients and their care in palliative and end-of-life care research. This library is a resource for investigators wanting to identify relevant and high-quality instruments

The prevalence and pattern of chemotherapy-induced peripheral neuropathy among women with breast cancer receiving care in a large community oncology practice

Purpose To describe the prevalence, severity, and risk factors of chemotherapy-induced peripheral neuropathy (CIPN) and its impact on function and quality of life (QOL) among women treated for breast cancer in a large U.S. Community Oncology practice. Methods Women previously treated with taxane-based chemotherapy for early-stage breast cancer completed the EORTC QLQ–C30, QLQ–BR23, and QLQ–CIPN20. Subscales are scored 0–100; higher scores indicate greater symptom severity. Pre-specified hypotheses were tested. Results 126 women with mean age 56.7 years (SD 11.8) were stage I–II (79.4%) or stage III (20.6%) at the time of the survey; 65.1% were White and 27.8% were Black or African American. The mean time since last taxane chemotherapy cycle was 144.9 weeks (SD 112.9). 73.0% reported having CIPN. QLQ–CIPN20 mean scores for the sensory, motor, and autonomic subscales were 18.9 (SD 23.1), 18.6 (SD 18.7), and 17.1 (SD 21.8), respectively. CIPN symptom severity was negatively correlated with global health status/QOL and physical and role functioning (range of r = -0.46 to -0.72). It was not associated with age, body mass index, diabetes, or cumulative taxane dosage, but was greater for Black or African American women (e.g., sensory, p<0.002). CIPN sensory impairment was marginally greater for patients treated with paclitaxel compared to docetaxel (p<0.064). Conclusions CIPN was prevalent in this community oncology practice and significantly impacts function and QOL. These data highlight the importance of developing methods to mitigate CIPN, and for screening for CIPN particularly among Black or African American women

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

Associations between prostate cancer-related anxiety and health-related quality of life

There are uncertainties about prostate cancer‐related anxiety's (PCRA) associations with health‐related quality of life (HRQOL) and major depression, and these could affect the quality of mental healthcare provided to prostate cancer patients. Addressing these uncertainties will provide more insight into PCRA and inform further research on the value of PCRA prevention. The goals of this study were to measure associations between PCRA and HRQOL at domain and subdomain levels, and to evaluate the association between PCRA and probable (ie, predicted major) depression