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PRO-CTCAE Face-To-Face Meeting #2 Advancing the Science of Adverse Symptom Monitoring in Cancer Treatment Trials. Tito Mendoza, PhD Thomas Atkinson, PhD Development of PRO-CTCAE Items May 24, 2010 National Cancer Institute Rockville, MD. Task 2: Item development.
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PRO-CTCAE Face-To-Face Meeting #2Advancing the Science of Adverse Symptom Monitoring in Cancer Treatment Trials Tito Mendoza, PhD Thomas Atkinson, PhD Development of PRO-CTCAE Items May 24, 2010 National Cancer Institute Rockville, MD
Task 2: Item development Input and expertise from multidisciplinary participants in various institutions Clinical trial design, health research, psychometrics, survey design, biostatistics, health literacy MSKCC MD Anderson Mayo DFCI FDA NCI Patient advocate
Identification of CTCAE items amenable to patient reporting 1. Laboratory (non-subjective; assessment requires equipment) 2. Measurable (non-subjective; assessment requires technical training) 3A. Primarily subjective phenomena, without observable component 3B. Primarily subjective phenomena, with observable component 3C. Primarily observable phenomena, with subjective component
Selection of PRO-CTCAE items: initial steps Identified existing PRO instruments that could supply items to be used as PRO-CTCAE items Conducted literature review for each symptom term from the CTCAE Searched and reviewed identified publications’ references Searched for non–symptom-specific and health-related quality of life instruments Considered single-item and multi-item questionnaires from cancer-specific and non–cancer-specific populations
Selection of PRO-CTCAE items:requirements and procedures • Appropriate and simple language patient terms were used as much as possible • Systematic review results were presented and discussed by the Task 2 committee members to select optimal initial draft patient terms • Discussions were facilitated using secondary analyses of patient-reported datasets • M. D. Anderson Symptom Inventory (MDASI) data from MD Anderson • Symptom Tracking and Reporting (STAR) system data from MSKCC • Patient Reported Outcomes Measurement Information System (PROMIS) initiative data from the NCI
Information systematically abstracted from publications and instruments for each symptom Available intensity/severity items for each symptom of interest Available interference items for each symptom Available frequency items for each symptom Source instrument of each candidate item Exact verbiage of question and response options for each candidate item Patient cognitive interviewing results from development of these questions, with particular attention to the rationale for selection (or rejection) of specific terms, based on patient responses Measurement properties available for each item: validity, reliability, sensitivity, clinical relevance of score changes, recall period Correlations available for each item with other measures of the symptom or measures of overall health state or disease status
PRO-CTCAE review template • Table 1. CTCAE v3 Item (updated to V4 later) • Table 2. Dimensions included in CTCAE v3 Items (updated to V4 later) • Table 3. Items From Multisymptom Instruments for (name symptom here) and Related Concepts • Table 4. Items From Single-Symptom Instruments for (name symptom here) and Related Concepts • Table 5. Terms Selected for Severity Item (Pre-Cognitive Interviewing) • Table 6. Terms Selected for Secondary Item(s) (if applicable) • Supplementary information
Design of question structures and response option formats for items Which attributes to include? MDASI, STAR and PROMIS datasets were used to evaluate the degree to which asking about different attributes of the same symptom is statistically redundant vs. provides added information (e.g., does asking patients about frequency of nausea add information beyond asking about severity alone).
Design of question structures and response option formats for items Which response option format to use? Previously noted systematic review of existing questionnaires was used to identify the spectrum of formats used in existing PRO instruments A separate literature review was conducted to characterize the scientific evidence, strengths, and limitations of the various available response-option formats
Generic question structures and response options for PRO-CTCAE items
PRO-CTCAE Items • Number of dimensions per symptom varies from 1 to 3 • Pain has 3 dimensions (frequency, severity, and interference) • Shortness of breath has 2 dimensions (severity and interference) • Hoarseness has 1 dimensions (severity) • 78 CTCAE v4.0 items • 125 PRO-CTCAE questions were drafted
Determination of “Core” PRO-CTCAE symptom items – data sources Five data sources were reviewed to identify prevalent adverse symptoms that are important to patients and clinicians across cancer populations: PRO data from 23,553 patients in cancer clinical trials via the European Organisation for Research and Treatment (EORTC)’s QLQ-C30 instrument PRO data from the development of the Memorial Symptom Assessment Scale (MSAS) PRO data from the development of the M. D. Anderson Symptom Inventory (MDASI) Adverse event data via the NCI’s Adverse Event Expedited Reporting System (AdEERS) and Clinical Data Update System (CDUS) for all phase II and III clinical trials sponsored by the NCI between 2005-2009 (unpublished, internal NCI data) Adverse event data in the 29 most recent clinical trials in the North Central Cancer Treatment Group (unpublished, internal NCCTG data)
Determination of “Core” PRO-CTCAE symptom items Symptoms were reviewed and compared to determine the most common adverse symptoms of any severity and the most common symptoms of high severity Symptom considered as common were those reported by >10% of patients via the QLQ-C30, MSAS, or MDASI; or those reported by staff on behalf of >1% of patients via the CTCAE Inclusion of these Core items across trials is intended to facilitate systematic screening for prevalent and important symptoms By administering identical Core items across trials, cross-study comparisons of the patient experience with treatment could be facilitated (i.e., comparative effectiveness/safety analyses)
PRO-CTCAE items, beta version 1.0 • Initially identified 77 CTCAE items amenable to PRO from CTCAE v3.0 • 78 items were identified amenable to PRO from CTCAE V4.0 • For the CTCAE v4.0 items depression and irregular menstruation, two PRO-CTCAE symptoms were mapped to each in order to capture a broader spectrum of patient experiences. Thus, a total of 80 PRO-CTCAE symptoms are mapped to the 78 CTCAE v4.0 items • 125 PRO-CTCAE questions were drafted (e.g. sensory neuropathy = numbness and tingling) • 18 “Core” symptom items were identified • Attributes of symptoms to be assessed have been determined • Verbal descriptor scale was selected • A 7-day recall period was selected
PRO-CTCAE items, updated May 2010 • 81 PRO-CTCAE symptom items • 126 PRO-CTCAE questions • 20 “Core” symptom items
PRO-CTCAE items, beta version 1.0 sample items Please answer the following questions about your symptoms. In the last 7 days, did you miss an expected menstrual period: Yes / No In the last 7 days, how OFTEN did you have aching joints: Never, Rarely, Occasionally, Frequently, Almost Constantly In the last 7 days, what was the SEVERITY of your aching joints at their WORST: None / Mild / Moderate / Severe / Very severe In the last 7 days, how much did aching joints INTERFERE with your daily activities: Not at all / A little bit / Somewhat / Quite a bit / Very much In the last 7 days, how much hair loss have you experienced: None at all / A little bit / Somewhat / Quite a bit / Very Much
