The construction and evaluation of item banks to measure unidimensional constructs of health-related quality of life (HRQOL) is a fundamental objective of the Patient-Reported Outcomes Measurement Information System (PROMIS) project. Item banks will be used as the foundation for developing short-form instruments and enabling computerized adaptive testing. The PROMIS Steering Committee selected 5 HRQOL domains for initial focus: physical functioning, fatigue, pain, emotional distress, and social role participation. This report provides an overview of the methods used in the PROMIS item analyses and proposed calibration of item banks. Analyses include evaluation of data quality (eg, logic and range checking, spread of response distribution within an item), descriptive statistics (eg, frequencies, means), item response theory model assumptions (unidimensionality, local independence, monotonicity), model fit, differential item functioning, and item calibration for banking. Summarized are key analytic issues; recommendations are provided for future evaluations of item banks in HRQOL assessment.

In cancer clinical trials, adverse events (AEs) are collected and reported using the US National Cancer Institute’s (NCI’s) Common Terminology Criteria for Adverse Events (CTCAE).¹ The CTCAE is a library of items representing 790 discrete AEs, each graded using an ordinal severity scale.² Approximately 10% of AEs in the CTCAE are symptoms (eg, nausea, sensory neuropathy), which in trials have historically been reported by clinical investigators.³ However, there is empirical evidence that collection of this information directly from patients improves the precision and reliability of symptomatic AE detection in trials^4-9and is feasible.^10,11 Moreover, there is substantial evidence that clinical investigators may miss up to half of patients’ symptomatic AEs.^5,6,12,13

The National Cancer Institute’s Symptom Management and Health-Related Quality of Life Steering Committee held a clinical trials planning meeting (September 2011) to identify a core symptom set to be assessed across oncology trials for the purposes of better understanding treatment efficacy and toxicity and to facilitate cross-study comparisons. We report the results of an evidence-synthesis and consensus-building effort that culminated in recommendations for core symptoms to be measured in adult cancer clinical trials that include a patient-reported outcome (PRO). We used a data-driven, consensus-building process. A panel of experts, including patient representatives, conducted a systematic review of the literature (2001–2011) and analyzed six large datasets. Results were reviewed at a multistakeholder meeting, and a final set was derived emphasizing symptom prevalence across diverse cancer populations, impact on health outcomes and quality of life, and attribution to either disease or anticancer treatment. We recommend that a core set of 12 symptoms—specifically fatigue, insomnia, pain, anorexia (appetite loss), dyspnea, cognitive problems, anxiety (includes worry), nausea, depression (includes sadness), sensory neuropathy, constipation, and diarrhea—be considered for inclusion in clinical trials where a PRO is measured. Inclusion of symptoms and other patient-reported endpoints should be well justified, hypothesis driven, and meaningful to patients. This core set will promote consistent assessment of common and clinically relevant disease- and treatment-related symptoms across cancer trials. As such, it provides a foundation to support data harmonization and continued efforts to enhance measurement of patient-centered outcomes in cancer clinical trials and observational studies.

The impact of cancer on health-related quality of life (HRQOL) is poorly understood because of the lack of baseline HRQOL status before cancer diagnosis. To our knowledge, this is the first population-based study to quantify the nature and extent of HRQOL changes from before to after cancer diagnosis for nine types of cancer patients and to compare their health with individuals without cancer. The Surveillance, Epidemiology, and End Results cancer registry data were linked with the Medicare Health Outcomes Survey (MHOS) data; data were collected from Medicare beneficiaries who were aged 65 years and older from 1998 through 2003. Cancer patients (n = 1432; with prostate, breast, colorectal, lung, bladder, endometrial, or kidney cancers; melanoma; or non-Hodgkin lymphoma [NHL]) were selected whose first cancer diagnosis occurred between their baseline and follow-up MHOS assessments. Control subjects without cancer (n = 7160) were matched to cancer patients by use of propensity scores that were estimated from demographics and comorbid medical conditions. Analysis of covariance models were used to estimate changes in HRQOL as assessed with the Medical Outcomes Study Short Form-36 survey (mean score = 50, SD = 10). All statistical tests were two-sided. Patients with all cancer types (except melanoma and endometrial cancer) reported statistically significant declines in physical health (mean scores: prostate cancer = -3.4, 95% confidence interval [CI] = -2.5 to -4.2; breast cancer = -3.5, 95% CI = -2.5 to -4.5; bladder cancer = -4.3, 95% CI = -2.5 to -6.1; colorectal cancer = -4.4, 95% CI = -3.3 to -5.5; kidney cancer = -5.7, 95% CI = -3.2 to -8.2; NHL = -6.7, 95% CI = -4.4 to -9.1; and lung cancer = -7.5, 95% CI = -5.9 to -9.2) compared with the control subjects (mean score = -1.8, 95% CI = -1.6 to -2.0) (all P < .05). However, only lung (mean score = -5.4, 95% CI = -3.5 to -7.2), colorectal (mean score = -3.5, 95% CI = -2.2 to -4.7), and prostate (mean score = -2.8, 95% CI = -1.8 to -3.7) cancer patients showed statistically significant decreases in mental health relative to the mean change of the control subjects (mean score = -1.2, 95% CI = -0.9 to -1.4) (all P < .05). These findings provide validation of the specific deleterious effects of cancer on HRQOL and an evidence base for future research and clinical interventions aimed at understanding and remediating these effects.