Patient reported outcomes in view of symptom experience of late effects and self-management of adult long-term survivors after allogeneic haematopoietic stem cell transplantation - a mixed methods study

Even years after allogeneic stem cell transplantation, recipients face a continuing risk of developing serious late effects. Previous studies have focused on the pathophysiological understanding of late effects, as well as on treatment and disease-related prediction of long-term post-transplant complications. In recent years, patient-reported outcomes (PROs) have been recognized as an invaluable source of information on the evolution of patients’ conditions. To date, however, few studies have used PRO data to focus on patients’ perspectives of late effects, symptom experiences or self-management strategies. Indeed, at the time of our preliminary research, no PRO instrument yet existed to measure late effect symptom experiences, and no investigations had yet focussed on a comprehensive set of patient self-management tasks, i.e., their day-to-day management of chronic conditions to maintain daily life activities and improve health behaviours. This doctoral research program examined patients’ self-management in view of symptom experience and lifestyle. More specifically, this thesis consists of six research articles, each addressing a specific aspect of these topics.
ARTICLE 1: UNDERSTANDING THE IMPORTANCE OF USING PATIENT REPORTED OUTCOME MEASURES IN PATIENTS WITH IMMUNE THROMBOCYTOPENIA
The first paper illustrates the value of using PROs to gather patient perspectives on the experience of a haematological disease–exemplified in immune thrombocytopenia–and summarizes the steps necessary to develop an effective PRO instrument. It also discusses challenges to the integration of PROs into research and clinical practice.
ARTICLE 2: LINGUISTIC AND CONTENT VALIDATION OF A GERMAN-LANGUAGE PRO-CTCAE-BASED PATIENT-REPORTED OUTCOMES INSTRUMENT TO EVALUATE THE SYMPTOM EXPERIENCE IN SURVIVORS OF ALLOGENEIC HAEMATO¬POIETIC STEM CELL TRANSPLANTATION
The second article describes the development of the PROVIVO questionnaire - a new PRO instrument developed to measure late-effect symptom experience. Based on the PRO-CTCAE item library, the PROVIVO instrument was designed, refined, and prepared for use in its target population according to Food and Drug Agency (FDA) guidance for PRO instrument development 14 and state-of-the-art recommendations for translation. Throughout the development process, we involved patients as well as expert clinicians. To test the clarity and acceptance of item terms in the user population, we applied cognitive debriefings, the results of which demonstrated that items were fully understandable and relevant to the SCT survivor experience.
ARTICLE 3: SYMPTOM EXPERIENCE OF LATE EFFECTS AFTER ALLOGENEIC HAEMATOPOIETIC STEM CELL TRANSPLANTATION: REFINEMENT AND PRELIMINARY VALIDITY TESTING OF THE PROVIVO INSTRUMENT FOR CONSTRUCT VALIDITY AND RELATIONS TO OTHER VARIABLES
In the third paper we reported on the refinement and preliminary validity testing of the newly developed PROVIVO instrument. Focussing on construct validity and relations to other variables, preliminary validity was explored in accordance with the “Standards for Educational and Psychological Testing”. An exploratory factor analysis revealed an eight-factor model explaining 57.05% of variance. Cronbach's alphas indicated that internal consistency reliability was good for the entire scale (.90), but only acceptable for the eight factor scores (.53-.82). Additional evidence supports relations between variables, e.g., between the number of symptoms and cGVHD occurrence, and between the number of late effects and performance status.
ARTICLE 4: DIFFERENCES IN HEALTH BEHAVIOURS BETWEEN RECIPIENTS OF ALLOGENEIC HAEMATOPOIETIC STEM CELL PLANTATION AND THE GENERAL POPULATION: A MATCHED CONTROL STUDY
Our fourth article identifies and describes considerable differences between SCT patients’ health behaviours and those of the general Swiss population, including several specific issues in medication taking behaviour. To our knowledge this is the first study to provide population-based data on the prevalence of health behaviours among SCT survivors in Switzerland. One particular strength is its case-match control design, i.e., via propensity scoring, each survivor was matched with a control from a representative sample of the Swiss population. The study results were mixed: survivors were most likely to adopt beneficial health behaviours regarding not smoking and low alcohol consumption; however, relative to the general population, a considerable group engaged in unfavourable behaviours, particularly regarding physical activity and diet.
ARTICLE 5: MEDICATION NON-ADHERENCE TO IMMUNO–SUPPRESSANTS AFTER ALLOGENEIC STEM CELL TRANSPLANTATION IS ASSOCIATED WITH CGVHD: PROVIVOMED – A MULTICENTRE CROSS-SECTIONAL STUDY
Among health behaviours, medication adherence to immunosuppressants (IS) is crucial: correct intake is essential to prevent and treat cGVHD. As no previous study had investigated the prevalence and consequences of post-SCT medication non-adherence (MNA), our fifth paper focusses on medication nonadherence and its associations to cGVHD. For the first time, we showed a relation between medication nonadherence and cGVHD grade, thereby highlighting a need for targeted interventions. In particular, patients prone to taking nonadherence and dose reduction were more likely to have moderate or severe cGVHD. We also found that those taking higher numbers of IS medications are more likely to be non-adherent. The converse is also true: IS nonadherence is less prevalent among those taking fewer co-medications.
ARTICLE 6: NURSES’ PRACTICE PATTERNS IN RELATION TO ADHERENCE ENHANCING INTERVENTIONS IN STEM CELL TRANSPLANT CARE: A SURVEY FROM THE NURSES GROUP OF THE EUROPEAN GROUP FOR BLOOD AND MARROW TRANSPLANTATION
As reducing MNA prevalence demands a clear understanding of healthcare providers’ medication self-management support practice patterns, these were the focus of our sixth and final paper. Concerning nurses’ assessment and support of medication adherence, our evaluation of their current practice patterns shows that they most often apply educational strategies. However, state-of the art evidence suggests that educational interventions alone have limited efficacy, favouring instead a combination of educational, behavioural and psychological interventions. Therefore, resources devoted to optimizing healthcare providers’ adherence support competencies would be a worthwhile investment.