Doctor of Philosophy / Department of Statistics / Gary L. Gadbury / The potential for high variability in treatment effects across individuals has been recognized as an important consideration in clinical studies. Surprisingly, little attention has been given to evaluating this variability in design of clinical trials or analyses of resulting data. High variation in a treatment’s efficacy or safety across individuals (referred to herein as treatment heterogeneity) may have important consequences because the optimal treatment choice for an individual may be different from that suggested by a study of average effects. We call this an individual qualitative interaction (IQI), borrowing terminology from earlier work - referring to a qualitative interaction (QI) being present when the optimal treatment varies across ‘groups’ of individuals. At least three techniques have been proposed to investigate treatment heterogeneity: techniques to detect a QI, use of measures such as the density overlap of two outcome variables under different treatments, and use of cross-over designs to observe ‘individual effects.’ Connections, limitations, and the required assumptions are compared among these techniques through a quantity frequently referred to as subject-treatment (S-T) interaction, but shown here to be the probability of an IQI (PIQI). Their association is studied utilizing a potential outcomes framework that can add insights to results from usual data analyses and to study design features to more directly assess treatment heterogeneity. Particular attention is given to the density overlap of two outcome variables, each representing an individual’s ‘potential’ response under a different treatment. Connections are made between the overlap quantified as the proportion of similar responses (PSR) and the PIQI. Given a bivariate normal model, the maximum PIQI is shown to be an upper bound for ½ the PSR. Additionally, the characterization of a conditional PSR allows for the PIQI boundaries to be developed within subgroups defined over observable covariates so that the subset contribution to treatment heterogeneity may be identified. The possibility of similar boundaries is explored outside the normal model using the skew normal distribution. Furthermore, a bivariate PIQI is developed along with its PSR counterpart to help characterize treatment heterogeneity resulting from a bivariate response such as the efficacy and safety of a treatment.

The field of augmentative and alternative communication (AAC) has evolved since the 1970s, consequently there now exists a group of adults with cerebral palsy (CP), in the UK, who are life-time users of AAC prescribed as an intervention for their complex communication impairments. Ten adults, aged between 20-55 years, participated in conversations about their unique life experiences and aspirations, using AAC, including voice output communication aids (VOCAs). The ability and opportunity to interact and communicate personal accounts has significance for conceptualizing outcomes of intervention. Clinical practice informed this research project. A qualitative research design was employed to explore questions about the extent to which adult aided communicators talk about their lives, aspirations and opinions; the past life experiences participants talk about and finally how they talk about their quality of life. Conversational-styled, semi-structured interviewing using literature-guided questions yielded rich interactional data. A discourse analytical approach to the 34 interviews was taken. Findings identified a number of ordinary interactional features and discourses. Aided communicators used multimodal communication to interact and converse, positioning through their contributions as assertive speakers and engaged recipients. Interactional turns were managed with participants using unaided communication signals as conversational continuers. Participants demonstrated how to manage others who speak on their behalf. Examples of interactional repair were noted when participants pre-empted breakdown. Managing novel utterances was a feature with unexpected responses challenging the listener’s position. Participants constructed VOCA-mediated utterances to share long-term memories, worries, satisfaction with life, and aspirations. Aspirations included community ambitions and creating fulfilling daily lives. Some participants expressed frustration but balanced this against a position of contentment. Some participants also demonstrated personal responsibility and positioned themselves through their talk as contributors to communities. Recommendations for clinical practice are suggested that include the provision of adult clinical services and interaction focused intervention for adult aided communicators with cerebral palsy.