Susan Yount

The Patient-Reported Outcomes Measurement Information System (PROMIS): progress of an NIH Roadmap cooperative group during its first two years.

Background:The National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS) Roadmap initiative (www.nihpromis.org) is a 5-year cooperative group program of research designed to develop, validate, and standardize item banks to measure patient-reported outcomes (PROs) relevant across common medical conditions. In this article, we will summarize the organization and scientific activity of the PROMIS network during its first 2 years. Design:The network consists of 6 primary research sites (PRSs), a statistical coordinating center (SCC), and NIH research scientists. Governed by a steering committee, the network is organized into functional subcommittees and working groups. In the first year, we created an item library and activated 3 interacting protocols: Domain Mapping, Archival Data Analysis, and Qualitative Item Review (QIR). In the second year, we developed and initiated testing of item banks covering 5 broad domains of self-reported health. Results:The domain mapping process is built on the World Health Organization (WHO) framework of physical, mental, and social health. From this framework, pain, fatigue, emotional distress, physical functioning, social role participation, and global health perceptions were selected for the first wave of testing. Item response theory (IRT)-based analysis of 11 large datasets supplemented and informed item-level qualitative review of nearly 7000 items from available PRO measures in the item library. Items were selected for rewriting or creation with further detailed review before the first round of testing in the general population and target patient populations. Conclusions:The NIH PROMIS network derived a consensus-based framework for self-reported health, systematically reviewed available instruments and datasets that address the initial PROMIS domains. Qualitative item research led to the first wave of network testing which began in the second year.

Evaluation of item candidates: The PROMIS qualitative item review

One of the PROMIS (Patient-Reported Outcome Measurement Information System) network’s primary goals is the development of a comprehensive item bank for patient-reported outcomes of chronic diseases. For its first set of item banks, PROMIS chose to focus on pain, fatigue, emotional distress, physical function, and social function. An essential step for the development of an item pool is the identification, evaluation, and revision of extant questionnaire items for the core item pool. In this work, we also describe the systematic process wherein items are classified for subsequent statistical processing by the PROMIS investigators. Six phases of item development are documented: identification of extant items, item classification and selection, item review and revision, focus group input on domain coverage, cognitive interviews with individual items, and final revision before field testing. Identification of items refers to the systematic search for existing items in currently available scales. Expert item review and revision was conducted by trained professionals who reviewed the wording of each item and revised as appropriate for conventions adopted by the PROMIS network. Focus groups were used to confirm domain definitions and to identify new areas of item development for future PROMIS item banks. Cognitive interviews were used to examine individual items. Items successfully screened through this process were sent to field testing and will be subjected to innovative scale construction procedures.

Relative to the general US population, chronic diseases are associated with poorer health-related quality of life as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS)

OBJECTIVES The Patient-Reported Outcomes Measurement Information System (PROMIS) allows assessment of the impact of chronic conditions on health-related quality of life (HRQL) across diseases. We report on the HRQL impact of individual and comorbid conditions as well as conditions that are described as limiting activity. STUDY DESIGN AND SETTING Data were collected through online and clinic recruitment as part of the PROMIS item calibration sample (n=21,133). Participants reported the presence or absence of 24 chronic health conditions and whether their activity was limited by each condition. RESULTS Across health status domains, the presence of a chronic condition was associated with poorer scores than those without a diagnosis, particularly for those individuals who reported that their condition was disabling. The magnitude of detriment in HRQL was more pronounced for individuals with two or more chronic conditions and could not be explained by sociodemographic factors. Patterns of HRQL deficits varied across disease and comorbidity status. CONCLUSION The impact of chronic conditions, particularly when experienced with comorbid disease, is associated with detriments in HRQL. The negative impact on HRQL varies across symptoms and functional areas within a given condition.

Patient-reported outcomes in randomized clinical trials: Development of ISOQOL reporting standards

PurposeTo develop expert consensus on a suite of reporting standards for HRQL outcomes of RCTs.MethodsA Task Force of The International Society of Quality of Life Research (ISOQOL) undertook a systematic review of the literature to identify candidate reporting standards for HRQL in RCTs. Subsequently, a web-based survey was circulated to the ISOQOL membership. Respondents were asked to rate candidate standards on a 4-point Likert scale based on their perceived value in reporting studies in which HRQL was a study outcome (primary or secondary). Results were synthesized into draft reporting guidelines, which were further reviewed by the membership to inform the final guidance.ResultsForty-six existing candidate standards for reporting HRQL results in RCTs were synthesized to produce a 40 item survey that was completed electronically by 161 respondents. The majority of respondents rated all 40 items to be either ‘essential’ or ‘desirable’ when HRQL was a primary RCT outcome. Ratings changed when HRQL was a secondary study outcome. Feedback on the survey findings resulted in the Task Force generalizing the guidance to include patient-reported outcomes (PROs). The final guidance, which recommends standards for use in reporting PROs generally, and more specifically, for PROs identified as primary study outcomes, was approved by the ISOQOL Board of Directors.ConclusionsISOQOL has developed a suite of recommended standards for reporting PRO results of RCTs. Improved reporting of PROs will enable accurate interpretation of evidence to inform patient choice, aid clinical decision making, and inform health policy.

Early Change in Patient-Reported Health During Lung Cancer Chemotherapy Predicts Clinical Outcomes Beyond Those Predicted by Baseline Report: Results From Eastern Cooperative Oncology Group Study 5592

PURPOSE To determine the ability of longitudinal patient-reported health (PRH) scores to enhance prediction of clinical outcomes beyond baseline scores. PATIENTS AND METHODS In 573 advanced non-small-cell lung cancer patients enrolled in a phase III clinical trial, we used baseline and 6-week follow-up PRH scores to predict best response to treatment, disease progression, and survival. Using regression analyses, we tested the predictive ability of the five subscales of the Functional Assessment of Cancer Therapy-Lung (physical, functional, social/family, emotional well-being, and the lung cancer subscale) as well as the trial outcome index (TOI) aggregate score. RESULTS After clinical factors were controlled for, baseline physical well-being (PWB) and TOI scores predicted all three clinical outcomes. A higher baseline PWB score was associated with a better response to treatment (odds ratio, 1.09; P <.001) and lower risk of death (risk ratio, 0.95; P <.001). Higher baseline TOI score was associated with a lower risk of disease progression (risk ratio, 0.98; P <.001). These two baseline predictors (PWB and TOI) were then used along with 6-week change scores to classify patients into four groups: low baseline-declined, low baseline-improved, high baseline-declined, and high baseline-improved. Patients with low baseline-declined PWB scores showed the worst responses to treatment and survived the shortest duration. Patients with low baseline-declined TOI scores had the shortest time to progression. CONCLUSION The physical aspects of baseline PRH and PRH change during chemotherapy are significant predictors of clinical outcomes in lung cancer. This has implications for patient stratification in clinical trials and may aid decision-making in clinical practice.

What are the most important symptom targets when treating advanced cancer? A survey of providers in the National Comprehensive Cancer Network (NCCN).

We derived a set of brief, clinically relevant symptom indices for assessing symptomatic response to chemotherapy for advanced bladder, brain, breast, colorectal, head and neck, hepatobiliary/pancreas, lung, ovarian, and prostate cancers. Questions were extracted from a multidimensional cancer quality of life (QOL) measurement system, the Functional Assessment of Cancer Therapy (FACT). Surveys of disease-related symptoms were presented to expert physicians and nurses at 17 National Comprehensive Cancer Network (NCCN) member institutions. In a two-step procedure, each expert narrowed the list to no more than five of the very most important to attend to when assessing the value of drug treatment for advanced disease. Symptoms endorsed at a frequency greater than chance probability were retained for the nine symptom indices. The resulting NCCN/FACT symptom indices are comprised of 6–15 items, depending on disease. Fatigue, pain, nausea, weight loss, worry about worsening condition, and contentment with current QOL were consistently selected by experts as priority symptoms across tumor sites. These nine tumor-specific symptom indices indicate the most important clinician-rated targets of chemotherapy for many advanced cancers. These results await validation in patient populations and examination of the extent to which changes in symptomatology translate into meaningful improvement to the patient.

Distress and Internalized Homophobia Among Lesbian Women Treated for Early Stage Breast Cancer

A convenience sample of 57 lesbian women who had been recruited for a study of adjustment to breast cancer completed measures of internalized homophobia, degree of disclosure of sexual orientation, social support, self-esteem, and distress. Consistent with our prediction, internalized homophobia related to greater distress. Contrary to our prediction, disclosure did not relate to lower distress. Path models were consistent with the position that internalized homophobia promotes distress through lower self-esteem and perceived unavailability of social support. However, the data were also consistent with a model in which low self-esteem leads to internalized homophobia by way of elevated distress. Internalized homophobia also related inversely to utilization of health care resources. Our discussion centers on the need for more information regarding this understudied population.

Assessment of Patient-Reported Clinical Outcome in Pancreatic and Other Hepatobiliary Cancers: The FACT Hepatobiliary Symptom Index

This studys aim was to develop and validate a symptom index derived from the Functional Assessment of Cancer Therapy-Hepatobiliary, a questionnaire measuring general and hepatobiliary disease specific aspects of quality of life. The item pool was narrowed to 26 questions that assess symptoms and function. Each of 95 hepatobiliary cancer experts narrowed the list to 5 of the most important to attend to when treating advanced hepatobiliary disease. Eight symptoms were endorsed by more than 20% of the experts (3 pain, 2 fatigue, nausea, weight loss, jaundice) and were named the FACT-Hepatobiliary Symptom Index-8 (FHSI-8). Among 51 hepatobiliary cancer patients, the FHSI-8 showed good internal consistency (0.79), test-retest reliability (r = 0.86), strong association with mood (r = -0.56), and patient differentiation by ECOG Performance Status Rating ( P < 0.0001) and treatment status ( P = 0.057). Symptom scaling in diseases such as hepatobiliary cancer is feasible and may provide an efficient, clinically-relevant endpoint for following groups over time.

Fertility Preservation and Adolescent Cancer Patients: Lessons from Adult Survivors of Childhood Cancer and Their Parents

Building on 40 years of progress in cancer detection and treatment, survival rates for childhood cancers have risen from 20 % to almost 80 % [1,2]. Approximately 270,000 Americans are childhood cancer survivors and, by 2010, an estimated 1 in every 250 adults will be living with a history of childhood cancer [2,3]. The early and late effects of treatment are beginning to take on greater importance for survivors, their families and providers [4]. Increasing numbers of childhood cancer survivors are beginning to face a new challenge in returning to normalcy after cancer. Infertility is one of the most common chronic medical problems reported by childhood cancer survivors [5] and can be a primary concern particularly among female survivors [6]. Female infertility has biological and psychosocial implications that cannot be easily addressed given the ethical and legal questions surrounding fertility preservation [7–9]. Recent advances in fertility preservation may soon offer potential methods for females of all ages to protect their reproductive capacity from damaging radiation and/or chemotherapy [10]. Current literature focuses on the further development of preservation techniques and the numerous ethical and legal questions, but little knowledge is available on the attitudes and opinions of childhood cancer patients and their parents regarding fertility preservation. Progress is being made in understanding the fertility issues that women may face after treatment. Infertility as an isolated health problem can be emotionally devastating for a woman [11] and is often viewed as a loss of one’s sense of femininity [12]. The risk of infertility touches on the most intimate aspects of a woman’s life after cancer, particularly her relationships, future plans for a family, and concerns about pregnancy and birth [4,12–16]. For cancer survivors who may be dealing with additional physical and emotional concerns, infertility may add yet another concern to an already lengthy list of fears and worries [17]. Some survivors describe that the loss of fertility can be as painful as facing cancer itself [15,18]. The situation is further complicated by the fact that female cancer survivors, particularly pediatric cancer patients, lack clear-cut options to address their fertility that are available to their male counterparts. Advancements in semen cryopreservation and intracytoplasmic sperm injection (ICSI) have revolutionized the reproductive outlook of male patients who have reached puberty [19]. Recent advances in reproductive science are beginning to change what is possible for female survivors as well. Traditionally, few options existed for female cancer patients who may want to have their own biological children in the future. The only two established techniques women have for fertility preservation are protecting the ovaries from radiation and emergency in vitro fertilization (IVF) [20,21]. While protecting a patient’s ovaries has become common practice, emergency IVF cannot be offered to patients diagnosed with cancer before puberty because mature oocytes cannot be collected [22]. The promise for female patients with childhood cancer lies in the strides made toward ovarian transplantation and in vitro follicle maturation. Ovarian transplantation involves the removal and cryopreservation of ovarian tissue before treatment and the reintroduction of tissue after treatment, either orthotopically or heterotopically, such as in muscle or subcutaneously [23]. Researchers have demonstrated that transplantation of cryopreserved ovarian tissue has led to human embryonic development when accomplished heterotopically [24] and to a live birth after orthotopic transplantation [25]. Another promising method of fertility preservation is in vitro maturation of immature oocytes. Similar to ovarian transplantation, ovarian tissue is removed and cryopreserved before fertility-threatening treatment. Once a woman is prepared to have a child, follicles can be isolated from the thawed tissue, matured in vitro in a three-dimensional culture system, and the mature oocyte can be fertilized through IVF. Murine oocytes have been collected from in vitro grown follicles, matured, and fertilized in vitro, which has resulted in live births [26]. Human trials, where one ovary is laparoscopically removed before treatment, are being conducted on adult patients in order to begin the experimental process of perhaps one day delivering this option to female cancer patients. As research begins to enter the clinical arena, a large number of unanswered questions remain regarding the application of the procedures, the legal and ethical considerations involved, and the receptiveness of patients and their families to fertility preservation. Thus far, very few studies have considered the viewpoints of childhood cancer patients and their parents [27]. Since decisions regarding fertility preservation must be made before treatment begins, parents, physicians, and patients are required to make a complex decision in a short amount of time during an extremely stressful situation, similar to the anxiety involved in the informed consent process of clinical cancer research trials [28]. In order for fertility preservation to become a realistic and valued addition to the treatment of childhood cancer patients, a better understanding of the decision-making process that parents and their children go through at the time of diagnosis and their interest in fertility preservation is needed. Further, a more thorough exploration of the patients’ and parents’ thoughts regarding the child’s fertility at the time of diagnosis as well as later in the patient’s life will be valuable in the continued advancement and eventual application of fertility preservation.

Measuring Health-Related Quality of Life in Leukemia: The Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) Questionnaire

OBJECTIVE Develop and validate a health-related quality-of-life (measure for patients with acute and chronic leukemia. METHODS The study consisted of two phases: scale construction and scale validation. For the item-generation phase, a summary of the literature combined with qualitative results from item-generation interviews with 29 acute or chronic leukemia patients and 16 health care providers yielded an initial item pool reflecting leukemia-specific concerns and symptoms. Items underwent iterations of review and reduction according to defined retention criteria to support content validity, as defined by priority concerns of patients. Seventeen final leukemia-specific items were combined with the Functional Assessment of Cancer Therapy-General to create the FACT-Leukemia (FACT-Leu) scale. For the validation phase, 79 individuals with acute or chronic leukemia completed questionnaires at three time points. RESULTS All FACT-Leu subscale and aggregated scores showed high internal consistency (αs ranging from 0.75 to 0.96). Test-retest reliability was adequate for all subscales (intraclass correlation range 0.765-0.890). The FACT-Leu scale demonstrated good convergent validity, with significant correlations with quality-of-life criteria and performance status, in the expected direction. FACT-Leu subscale scores were significantly different among the three performance status change groups, suggesting good responsiveness to change. CONCLUSIONS The FACT-Leu scale is a valid, reliable, and efficient measure of leukemia-specific health-related quality of life for acute and chronic disease.