Cross-cultural translation of existing instruments has become an essential component of research methodology in preparation for multinational clinical trials. However, to improve cross-cultural equivalence, it is important to incorporate an awareness of cross-cultural issues prior to beginning translation work. This workshop will cover: 1) cross-cultural instrument development including a comparison of sequential, parallel, and simultaneous approaches with a special focus on WHOQOL methods; 2) types of cross-cultural equivalence and possible threats to validity if equivalence is not achieved; 3) instrument translation and adaptation methodologies; 4) use of qualitative evaluation methods such as cognitive interviewing techniques to assess linguistic validity and cross-cultural equivalence of translated questionnaires. Finally, we will discuss strategies to use to improve equivalence, such as the decentered model to refine the source instrument and alternatives when modification of the original instrument is not feasible. Workshop structure includes 65% lecture, 25% Q&A and 10% interactive exercises on translation methodology and cognitive interviewing.
Level: Basic

Workshop 2
COPING WITH THE VALIDATION REQUIREMENTS OF THE FDA PRO GUIDANCE: SCIENCE AND THE PRACTICAL OUTCOMES RESEARCHER
Instructors: William Lenderking, Michelle Stewart, Pfizer Inc, USA and Elizabeth Merikle, Pfizer Inc, Canada

This workshop will take off from the draft PRO guidance and consider the practical implications and scientific evidence supporting certain aspects of the guidance. In particular, we will focus on validation of patient reported outcome measures in light of the guidance on conceptual frameworks, conceptual models, and endpoint models. We will also consider the scientific evidence for the recommendations around the recall period. Practical, real-world examples/research dilemmas will be presented for discussion, and we will consider alternative solutions, as well as discussing the solution ultimately chosen. Questions to be considered include the following: What does the literature say about validation requirements for a scale that has been in use for decades but has obvious limitations? What constitutes sufficient validation? If a scale has been validated in a given study population, what are the validation requirements for applying it to a new population, according to both the FDA and the literature? What if your research team wants to administer a questionnaire on a weekly basis, and it has only been previously developed for monthly administration? Are there different aspects of health and functioning which might be optimally measured over different recall periods? Can measures with different recall periods be compared within the same study? Does it make sense to assess functioning on a daily basis, or should daily measurement be more appropriately reserved for symptoms?
Level: Basic

Workshop 3
CAPTURING PATIENT-REPORTED OUTCOMES ELECTRONICALLY: FROM E-PRO DESIGN TO IMPLIMENTATION
Instructors: Kellee Howard, Jennifer Petrillo, United BioSource Corporation, USA, Jacqueline Thong, CRF, Inc., USA, Meghan Werner and Nancy Kline Leidy, United BioSource Corporation, USA

With rapid improvements in technology comes the opportunity to increase the efficiency and effectiveness of gathering patient-reported outcomes (PROs) by electronically capturing these data. E-PROs involve a variety of techniques, including personal digital assistants (PDAs), interactive voice response systems (IVRS), and computer touch screens, each offering unique opportunities and challenges. This workshop will address critical issues in e-PROs, including selection of the appropriate technology, instrument development and validation, and the execution of studies involving e-technologies. We will give specific attention to the use of PDAs for gathering quality of life, symptom, and other data during random, daily, or weekly assessments in keeping with the recall needs of the underlying concept being measured.

During the first portion of the workshop, moderators will lead participants in a discussion of the following issues: types of concepts most and least suited to e-data capture, unique features of each format, the development or revision of instruments for use on PDAs, and the type and timing of data to track study progress and contribute to instrument evaluation. Item development, cognitive debriefing, and scoring options for e-PRO using PDAs will be addressed, as will issues related to patient and site training to optimize data quality. Examples from the literature, the field, and experience with the EXACT-PRO Initiative(1) will inform the discussion. During the second portion of the workshop, participants will be involved in a practical application of ePRO-PDA development and will engage in hands-on experience using PDAs pre-programmed with a variety of question formats suitable for e-PRO data capture.

Organization: 50% lecture and discussion, 35% in-class exercise, 15% Q&A

(1) The EXAcerbations of Chronic pulmonary disease Tool - The EXACT-PRO Initiative brings together industry, clinical, and regulatory (FDA) experts to develop a single PRO measure to evaluate exacerbations of COPD.
Level: Basic

Workshop 4
SPECIFYING PATIENT-REPORTED OUTCOME MEASURES FOR CHRONIC DISEASE SELF-MANAGEMENT PROGRAMS : A FRAMEWORK TO ENSURE THE RIGHT OUTCOMES ARE ASSESSED AT THE RIGHT TIME
Instructor: Richard Osborne, The University of Melbourne, Australia

The choice of the right range of measures to capture the intended and unintended effects of interventions can be difficult for researchers and evaluators alike. With the plethora of measures available and the wide range of possible intended impacts of interventions, including immediate and long term effects, a framework to support comprehensive assessment is warranted. This workshop will focus on chronic disease self-management and education programs as a working example of how to specify what needs to be measured and how this can be done. Such programs may have a wide range of immediate impacts (e.g., education/knowledge), intermediate impacts (e.g., empowerment, life quality) and longer term impacts (e.g., use of health services, reduction of symptoms).

Poor understanding and poor specification of the objective of an intervention leads to poor outcome measurement. Without a clear idea of what you are measuring, how can you measure it accurately? Consider social comparison, learning, changes in self image and the resulting change in perception (or response shift) which may attenuate participant s perceptions of disease severity. The workshop will include insights derived from the heiQ (Health Education Impact Questionnaire), the National Quality and Monitoring System for chronic disease health education and self-management programs now applied in 250+ organizations across disease groups and intervention types. In a high energy, fast moving and participatory workshop setting, attendees are encouraged to bring their current chronic disease program to the workshop for work-shopping so that the intended impact of their program can be clarified and a range of pertinent patient reported outcomes can be specified.
Level: Basic

Workshop 5
APPLICATIONS OF ITEM RESPONSE THEORY MODELING FOR IMPROVING HEALTH OUTCOMES MEASUREMENT - Part I
Instructors: Bryce Reeve, National Cancer Institute, USA and Chih-Hung Chang, Northwestern University, USA

There is a great need in health outcomes research to develop instruments or assessment tools that can accurately measure a person's health status with minimal response burden. This need for psychometrically sound and clinically meaningful measures calls for better analytical tools beyond the methods available from traditional measurement theory. Applications of item response theory (IRT) modeling have increased considerably because of its utility for instrument development and evaluation, assessment of measurement equivalence, instrument linking, item banking, and computerized adaptive testing. IRT models the relationship, in probabilistic terms, between a person's response to a survey question and their standing on a health construct (e.g., fatigue or depression) being measured. This information allows instrument developers to create reliable and efficient quality of life measures tailored for an individual or group or specific applications. This introductory workshop will discuss the basics of IRT models and applications of these models to improve health outcomes measurement. Illustrations from empirical data will be used throughout the presentation that focuses on measuring key health-related quality of life domains in different disease populations.
Level: Advanced

Workshop 6
ANALYSIS OF LONGITUDINAL STUDIES OF HRQOL STUDIES
Instructor: Diane Fairclough, University of Colorado Health Sciences Center, USA

This course will provide an introduction to the analysis of longitudinal studies in which missing data can be considered ignorable or missing at random (MAR). We will describe strategies for distinguishing between repeated measures models and growth curve models. Examples will be given for building and testing hypotheses for both simple and complex models including strategies for inclusion of time-varying covariates and interaction. We will discuss the use of polynomial and piecewise linear models as well as covariance structures and their interpretation. Then we will discuss models were missingness is assumed to be MAR conditional on auxiliary information. Finally we will discuss the concepts of moderation and mediation, and how to construct the appropriate models and tests. Handouts will include all slides. The workshop will include discussion (20% of time).
After completing this workshop, participants will be able to:
1. Choose between a repeated measures and growth curve model for the analysis of longitudinal data
2. Build models and construct hypothesis tests for both simple and complex models
3. Perform sensitivity analysis which incorporate ancillary information into the longitudinal models
4. Distinguish the concepts of moderation and mediations, set up the appropriate models for these concepts.
Participants should have experience with regression analysis.
Level: Advanced

Workshop 7
ADVANCED PSYCHOMETRIC METHODS, PART 1: USE OF EXPLORATORY AND CONFIRMATORY FACTOR ANALYSES IN PRO INSTRUMENT DEVELOPMENT AND EVALUATION
Instructors: Dennis Revicki and Donald Stull, United BioSource Corporation, USA

The development and psychometric evaluation of PRO instruments requires the application of a number of different techniques, including exploratory and confirmatory factor analysis (FA). We will provide a brief overview of psychometric analyses and then focus on the application of exploratory and confirmatory factor analysis for understanding of new measures and use of Structural Equation Modeling (SEM) for testing construct validity. Exploratory and confirmatory FA can be used to examine the relationships among items with a PRO measure or among different domains or multiple PRO measures. These techniques are useful for understanding the internal structure of PRO instruments and for understanding construct validity. This workshop will describe the main methods of FA and illustrate these methods with examples from the instrument development literature. SEM is a powerful analytic technique that combines FA and path analysis in a simultaneous, confirmatory approach. Using SEM, the researcher can specify and evaluate hypothesized relationships between observed and latent (unobserved) constructs as well as relationships among the latent variables. SEM can also estimate the reliability and validity of measurement models while explicitly modeling measurement error. A researcher constructs a structural model which specifies relationships among the latent variables to examine construct and criterion-related validity. If the observed covariances are consistent with the model-implied covariances, the researcher has evidence supporting the construct validity of the PRO measure. This workshop will demonstrate the main methods, testing assumptions and criteria, and provide examples to illustrate the methods of SEM.
Level: Advanced

Workshop 8
INTERPRETING UTILITY (PREFERENCE-BASED) MEASURES OF HEALTH-RELATED QUALTIY OF LIFE
Instructors: David Feeny, Kaiser Permanente, Northwest Region, USA, George Torrance, i3 Innovus, Canada, William Furlong and John Horsman, McMaster University, Canada

The Workshop will be at an advanced Level, focusing on the interpretation of utility scores from direct and multi-attribute (indirect) approaches to measurement. The direct approaches will include the visual analogue scale (Feeling Thermometer), time tradeoff, and standard gamble. Major multi-attribute utility measures will include the EQ-5D, Health Utilities Index (HUI), and Short-Form 6D. In addition, recent work on disease-specific utility instruments will be presented. The Workshop will include hands-on experience in the direct assessment of utility scores, completing questionnaires from several systems, and analyzing and interpreting the results. The interpretation of scores will be considered in the context of comparing groups at a point in time as well as comparing within-person change over time. Applications will be drawn from diverse settings including osteoarthritis of the knee, multiple sclerosis, total hip arthroplasty, and acute lymphoblastic leukemia. Evidence on clinically important differences will be discussed. Attendees should, at a minimum, have a basic knowledge of the conceptual foundations and practical approaches of the utility approach to assessing health-related quality of life.
Level: Advanced