Clinically Meaningful Change for Physical Performance: Perspectives of the ICFSR Task Force.

For clinical studies of sarcopenia and frailty, clinically meaningful outcome measures are needed to monitor disease progression, evaluate efficacy of interventions, and plan clinical trials. Physical performance measures including measures of gait speed and other aspects of mobility and strength have been used in many studies, although a definition of clinically meaningful change in performance has remained unclear. The International Conference on Frailty and Sarcopenia Research Task Force (ICFSR-TF), a group of academic and industry scientists investigating frailty and sarcopenia, met in Miami Beach, Florida, USA in February 2019 to explore approaches for establishing clinical meaningfulness in a manner aligned with regulatory authorities. They concluded that clinical meaningful change is contextually dependent, and that both anchor- based and distribution-based methods of quantifying physical function are informative and should be evaluated relative to patient-reported outcomes. In addition, they identified additional research needed to enable setting criteria for clinical meaningful change in trials.

Considerations for development of an evidence dossier to support the use of mobile sensor technology for clinical outcome assessments in clinical trials.

BACKGROUND: Mobile sensors offer enormous potential for the collection of informative clinical endpoints in clinical trials to support regulatory decision making and product labelling. There are currently no specific guidelines on the information needed to enable regulators to review and accept proposed endpoints derived from mobile sensors for use in drug development trials. OBJECTIVE: The purpose of this working group report is to recommend the structure and content of an evidence dossier intended to support whether a clinical endpoint derived from mobile sensor data is fit-for-purpose for use in regulatory submissions for drug approvals. EVIDENCE DOSSIER: The structure and content of a dossier to provide evidence supporting the use of a sensor-derived clinical endpoint is described. Sections include clinical endpoint definition and positioning, the concept of interest, the context of use, clinical validation and interpretation, study implementation, and analytical validity with sensor performance verification in support of the selected sensor. CONCLUSIONS: In the absence of definitive regulatory guidance, this report provides a considered approach to compiling a comprehensive body of evidence to justify acceptance of mobile sensors for support of new drug applications.

Health-related quality of life in rheumatoid arthritis patients in South India.

INTRODUCTION: Assessment of health-related quality of life (HRQL) has been gaining much importance in the care of rheumatoid arthritis (RA). This study was aimed at assessing the HRQL of patients with RA in South India. METHODS: HRQL of consenting RA patients, on disease-modifying anti-rheumatoid drugs (DMARDs) and attending a rheumatology clinic, was assessed using a self-filled Malayalam version of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) version 4 questionnaire. RESULTS: 50 patients were assessed out of 58 responses. The mean duration of the disease was 7.29 years. 46 patients (79.3 percent) had tried complementary and alternative medicines (CAM). The HRQL score in patients who were put on DMARDs within six months of symptoms was significantly higher (p-value is equal to 0.008). CONCLUSION: HRQL in patients treated early by DMARDs is significantly higher in this region, where a good proportion of patients seek the CAM for treatment of RA.

The functional assessment of cancer therapy-BRM (FACT-BRM): a new tool for the assessment of quality of life in patients treated with biologic response modifiers.

PURPOSE: This paper reports on the development and validation of two biologic response modifier (BRM) subscales for use with the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life (QOL) questionnaire. METHODS: Using the FACT-G as a base, 17 additional questions related to symptoms common to interferon and retinoid therapy were developed. Data collected at baseline (n = 191) and week 2 (n = 168) in a randomized trial of interferon +/- 13-cis-retinoic acid in advanced renal cell carcinoma patients were used to validate this measure. RESULTS: Using a combined empirical and conceptual approach, the 17 questions were reduced to 13 questions consisting of two subscales: 'BRM-physical' (7 items; baseline coefficient alpha(alpha) = 0.70; week-2 alpha = 0.75) and 'BRM-mental' (6 items; baseline alpha = 0.79; week-2 alpha = 0.78). Internal consistency of the trial outcome index (TOI) combining physical well-being, functional well-being and the BRM subscales, was 0.91 for baseline assessments and 0.92 for week 2. Discriminant validity was demonstrated for the TOI by its ability to differentiate among prognostic risk groups, and for the total FACT-G, TOI and total FACT-BRM scores by their ability to distinguish between groups differing in performance, response and toxicity status. CONCLUSIONS: The 'BRM-physical' and 'BRM-mental' subscales can be combined with the FACT-G to form the 'FACT BRM' scale, useful for measuring QOL in cancer patients who are receiving treatment with biologic response modifiers.

Quality of life and understanding of disease status among cancer patients of different ethnic origin.

Patients managed in European or North American cancer centres have a variety of ethnic backgrounds and primary languages. To gain insight into the impact of ethnic origin, we have investigated understanding of disease status and quality of life (QoL) for 202 patients. Patients completed questionnaires in their first language (52 English, 50 Chinese, 50 Italian, 50 Spanish or Portuguese), including the Functional Assessment of Cancer Therapy - General (FACT-G) QoL instrument, questions about disease status, expectations of cure and the language and/or type of interpretation used at initial consultation. Physicians also evaluated their status of disease and expectation of cure, and performance status was estimated by a trained health professional. The initial consultation was usually provided in English (except for 32% of Chinese-speaking patients); interpretation was provided by a family member for 34% of patients with limited English proficiency (LEP) and by a bilingual member of staff for 21%. Patients underestimated their extent of disease and overestimated their probability of cure (P=0.001 and <0.0001, respectively). Estimates of probability of cure by the English speakers were closer to those of their physicians than the other groups (P=0.02). English-speaking patients reported better and Italian-speaking patients poorer overall QoL (P<0.001 for Italian vs other groups). Performance status was correlated with QoL and most closely related with the extent of disease. Understanding of cultural differences is important for optimal management of patients with cancer.

Quality of life in breast cancer patients: validation of a FACT-B Malayalam version.

BACKGROUND: Recent advances in diagnosis and treatment of cancer have led to an increase in cancer survival, and hence, there is a greater emphasis on quality beside quantity of survival. Developing countries too have begun to recognize the need for monitoring quality of life (QOL). However, in most of the developing countries, a validated and reliable tool for the purpose is yet to be realized. MATERIAL AND METHOD: The functional assessment of chronic illness therapy (FACIT) system is a collection of QOL questionnaires targeted to measure QOL in chronic illness. The functional assessment of cancer therapy for breast cancer (FACT-B) was translated into the local language (Malayalam) and tested for validity and reliability. RESULTS: The tool thus developed showed substantial sensitivity, as does the source tool. The Cronbach's alpha for the total FACT-B was 0.87, which is similar to the alpha of 0.9 observed in the FACT-B English version. The mean FACT-B score was 94.3 compared to 112.8 for the source tool. CONCLUSION: The Malayalam translation of the FACT-B questionnaire was developed, tested and validated, and was found satisfactory in comparison to the source tool.

Translation and validation of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Version 4 quality of life instrument into traditional Chinese.

The need for a culturally sensitive instrument to assess quality of life (QOL) of patients in international oncology clinical trials has been well documented. This study was designed to evaluate the psychometric properties of the traditional Chinese translation (TCHI) of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Version 4. The FACT-BMT consists of the FACT-General and treatment-specific concerns of bone marrow transplantation. The Chinese translation follows the standard Functional Assessment of Chronic Illness Therapy (FACIT) translation methodology. Bilingual teams from the United States and Hong Kong reviewed the translation to develop a provisional TCHI FACT-BMT, which was then pre-tested by interviewing 20 native Chinese-speaking BMT patients in Hong Kong. The pre-test results indicated good content coverage and overall comprehensibility. A refined translation, taking into account patient comments, was validated by 134 BMT patients in Hong Kong. The results indicated the high internal consistency of the TCHI FACT-BMT scales, with Cronbach's alpha coefficients ranging from 0.71 (emotional well-being) to 0.92 (FACT-BMT total). The FACT-BMT also demonstrated good construct validity when correlated with SF-36 Health Survey scales. The QOL of Chinese BMT patients can now be evaluated using a well-validated international QOL instrument in their own language.

The Spanish National Institutes of Health-Chronic Prostatitis Symptom Index: translation and linguistic validation.

PURPOSE: The prominence of health related quality of life end points in international clinical research underscores the importance of well validated and translated measures to enable cross-cultural comparison. The National Institutes of Health (NIH)-Chronic Prostatitis Symptom Index (CPSI) assesses symptoms and health related quality of life in men with chronic nonbacterial, NIH type III prostatitis. To expand its use to Spanish speaking patients we performed a translation and linguistic validation. MATERIALS AND METHODS: The 9-item NIH-CPSI was translated into Spanish according to a standard methodology of 2 forward translations, 1 reconciled version, back translation of the reconciled version and 3 independent reviews by bilingual experts. The purpose of this methodology was to create a single universal Spanish version that would be acceptable to native Spanish speakers inside and outside of the United States. After the translation process the Spanish version was pre-tested in Argentina, Mexico, Spain and the United States. Patient responses were analyzed to identify necessary modifications. The internal consistency of the CPSI was evaluated using Cronbach's alpha. Pearson's product moment correlations were used to evaluate construct validity. RESULTS: Data were collected from chronic prostatitis patients, including 15 in Argentina, 15 in Mexico, 4 in the United States and 3 in Spain. The translation had high reliability overall and in all subscales (Cronbach's coefficient alpha = 0.81 to 0.94), and the subscales correlated well with each other (r = 0.76 to 0.97). However, patients expressed difficulty in distinguishing the response categories "a menudo" ("often") from "normalmente" ("usually") in question 3. We revised "a menudo" to "muchas veces" ("much of the time") and "normalmente" to "casi siempre" ("almost always") to improve the distinctiveness of response categories. CONCLUSIONS: The Spanish NIH-CPSI has high reliability as well as face and construct validity in Spanish speaking men from various countries. The Spanish NIH-CPSI permits cross-cultural comparisons of men with chronic nonbacterial prostatitis.

Cross-cultural validation of an international questionnaire, the General Measure of the Functional Assessment of Cancer Therapy scale (FACT-G), for Japanese.

The General Measure of the Functional Assessment of Cancer Therapy scale (FACT-G) was developed in an English-speaking culture (USA). To determine if FACT-G could be used in Japan, a cross-cultural validation was performed. The Japanese version was created through an iterative forward-backward translation sequence used throughout the FACT multi-lingual translation project. In evaluating psychometric testing, its construct validity was investigated by factor analysis and multi-trait scaling analysis. Clinical validity was estimated by known-groups comparison using stage, performance score (PS) and patient location, and validated longitudinally by PS. The FACT-G (version 3) was given to 180 patients with lung cancer. Analyses showed that the scales of Physical, Functional, Emotional Well-Being, and Relationship with Doctors were constructively valid in Japan. Japanese patients felt that familial relationships were different than those with friends and neighbors, indicating that the Social/Family Well-Being scale needed cultural adaptation. Two items concerning coping with illness and acceptance of illness did not load predictably onto their respective scales and were considered to be cross-culturally problematic. However, clinical validity demonstrated its sensitivity. Japanese version 4 has been improved to address the weakness in an attempt to become an instrument that is applicable across cultures.

Development of three African language translations of the FACT-G.

This pilot study investigated the feasibility of translating a quality of life instrument, the Functional Assessment of Cancer Therapy--General version (FACT-G) and the breast cancer version (FACT-B), which consists of the FACT-G plus 10 additional items, into three South African languages (Pedi, Tswana, and Zulu). The international, interdisciplinary research team hypothesized that we could develop reliable and valid translations, and that valuable information could be gleaned from the responses of the three groups of traditional African people, which could inform the Western-trained medical profession. Understanding of cross-cultural views of cancer including its diagnosis and treatment could lead to better communication between the two cultures (Western and Traditional) resulting in increased utilization of Western medical treatment and increased treatment compliance by three of the underserved black populations. A total of 167 respondents completed one of three translated questionnaires, which assessed the patients' quality of life in 5 domains: Physical Well-Being, Social and Family Well-Being, Relationship with Doctor, Emotional Well-Being, and Functional Well-Being, plus for breast cancer patients the additional items on the FACT-B. However, only the items from the FACT-G (the 'core' of the FACT-B) were statistically analyzed for this pilot project. Results showed that it was possible to develop a reliable instrument in the three languages by modifying the standard translation methodology. Translation of physical and functional concepts was most straightforward. Translation of emotional items posed some difficulty. As expected, based upon observations about cultural differences in social values and functioning, the Social/Family Well-Being subscale was problematic. Analysis of this subscale provides information on cultural differences which may be important to physicians desiring to effectively treat this population with sensitivity and dignity. Methodology may be generalizable to other third world patient populations in translation of existing health status questionnaires.

Using cross-cultural input to adapt the Functional Assessment of Chronic Illness Therapy (FACIT) scales.

Cross-cultural quality of life measurement and psychosocial assessment in oncology have become reality with the translation and international validation of quality of life questionnaires. The Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System, under development since 1987, produced its 4th version in November 1997. The FACIT system includes the Functional Assessment of Cancer Therapy (FACT), the Functional Assessment of Human Immunodeficiency Virus Infection (FAHI) and the Functional Assessment of Multiple Sclerosis (FAMS). These questionnaires were developed in North America and, to date, many have been translated into almost 30 languages. One of the strengths of this ongoing translation project is its use of input from patients, linguists, psychologists and physicians internationally to assure that the wording of Version 4 is more cross-culturally relevant and more sensitive to measuring the psychosocial impact of illness in cultures outside the United States. Statistical analysis, aggregation of patient comments, and comments from linguists and users of the translated versions are used as needed to revise item wording to ensure clarity and consistency across languages. A 'decentering' approach is also used to adapt the source (English language) document in response to problems encountered during its translation.

[Development of Japanese version of QOL questionnaire for bladder and prostate cancer patients using FACT-Bl and P: pilot study].

BACKGROUND: Quality of life (QOL) has been known to be a prognostic factor as well as the endpoint of treatment efficacy in many clinical fields. We have begun a US-Japan collaborative project introducing a QOL questionnaire, the FACT (Functional Assessment of Cancer Therapy), into Japan. We report on the translation process, results of the pilot study, and future plans for translating the Japanese version of the FACT subscales, FACT-Bl (for bladder cancer) and FACT-P (for prostate cancer). METHODS: The FACT translation procedure, which is quite rigorous, follows a four-step methodology. After completing the translations, we tested the translated FACT-G (general questionnaire) and subscales for bladder and prostate cancer patients. The questionnaires were tested on 30 outpatients at Tsukuba University Hospital (15 bladder, 15 prostate). The only eligibility requirement to participate in the study was a confirmed diagnosis of cancer of the bladder or prostate. RESULTS AND DISCUSSION: There was satisfactorily high internal consistency of FACT-G of both bladder and prostate cancer patients. FACT-Bl study included patients having undergone radical cystectomy as well as those who had not. Because not all items were answered by all patients, the Cronbach's alpha coefficient for the FACT-Bl subscale could not be computed. Further evaluation of the FACT-Bl concerning the surgical procedures affecting QOL is needed. We are currently planning to make the further refinement of the questionnaire in order to make it more suitable for bladder cancer patients. FACT-P subscale had an alpha coefficient of 0.82 and was determined to be useful in its present form.