Introduction: The scarcity of rigorous evidence regarding rare disease therapies contributes to uncertainty for stakeholders who make decisions about the use, prescription, or funding of such therapies. My dissertation objective was to integrate stakeholder perspectives and evidence related to how rare disease therapies are evaluated to better understand drivers of uncertainty in decision making and develop an evaluation framework for future evidence generation, synthesis, and decision support. Methods: To better understand the perceived challenges in generating robust treatment effectiveness evidence, and describe various methods for mitigating these challenges, I used a meta-narrative literature review. I also conducted focus group interviews with key rare disease stakeholders (patients/caregivers, physicians, and policy advisors) to elicit different perspectives on how evidence is generated, evaluated, and synthesized in the context of health care decision making, both at a personal and population level. Finally, I integrated the focus group findings with a targeted literature review to identify characteristics of rare diseases and their candidate therapies that may warrant special consideration in health technology assessment (HTA) and health care decision making. Findings: My dissertation data revealed three fundamental challenges in generating robust treatment effectiveness evidence for rare diseases: limitations in recruiting a sufficient sample; inability to account for clinical heterogeneity; and reliance on outcomes with unclear clinical relevance. Several methodological solutions have been proposed to overcome these challenges. In addition, study participants described different perspectives on how they choose to participate in and use research in their roles as health care users, care providers, and policy advisors. Notably, conventional wisdom that patients/caregivers participate in clinical research studies because of therapeutic misconception was not supported. Finally, focus group and literature review findings identified information that potentially warrants special consideration in future HTA specific to rare diseases, including characteristics of the disease, understanding of causal hypotheses relevant to the therapy, and complexities of cost-effectiveness given the high price of many rare disease therapies. Discussion: Together, the findings from this dissertation support an evaluation framework with eight key principles that aim to mitigate important aspects of uncertainty from various stakeholder perspectives and promote evidence-informed decision making about rare disease therapies.

As youth with disabilities age and transition to adulthood, they will often need to learn how to manage their healthcare. Siblings are members of the family who can provide support to their sibling with a disability, but their roles during transition have not been well described in the literature. Typically developing (TD) siblings identified that they require information and resources in their roles. The overall objectives of the research studies in this doctoral dissertation are: 1) to synthesize existing resources and programs to support TD siblings of individuals with a disability; and 2) to develop a deeper understanding about the experiences of TD siblings. The findings from these studies are summarized in six scholarly manuscripts prepared for peer review and publication. All studies were conducted in partnership with siblings with lived experiences. Results from the review and qualitative document analysis of online resources to support TD siblings (Chapter 2) identified that limited resources are available to support TD siblings with healthcare management of their sibling with a disability. The scoping review (with the protocol described in Chapter 3 and results presented in Chapter 4) identified that programs for TD siblings are focused on knowledge development and skill acquisition for the TD siblings themselves or on empowerment by training TD siblings in skills that they can apply with their sibling with a disability. In addition to synthesizing existing knowledge, the qualitative study provided an in-depth understanding of the experiences of TD siblings (with the protocol described in Chapter 5) in two distinct areas: their roles and responsibilities (Chapter 6) and the influence of their sibling and family relationships on their identity formation during developmental stages (Chapter 7). Overall findings from this dissertation suggest areas for future directions, including knowledge transfer to share synthesized resources with target audiences, co-creation of resources to support siblings in their roles, and enhancement of programs to involve siblings and the whole family. / Dissertation / Doctor of Philosophy (PhD) / As youth with a disability transition to adulthood, many will assume greater responsibility for their own health management, activities often supported by family members, including siblings. Little information is available about the roles that siblings have to their sibling with a disability in this process. Siblings have mentioned that they need information and resources for their roles. The purpose of this work is to summarize resources and programs in Canada and internationally for siblings, as well as better understand the experiences of siblings of an individual with a disability. The information from this work can be helpful by sharing the summary of resources with siblings and families, create new resources to support siblings of an individual with a disability, and build on programs that allow for siblings and the whole family to participate.

The author presents a case study for the development of an evidence synthesis service serving researchers outside of the health sciences at a large academic library. The purpose of this project was to highlight the importance of integrating existing core services and workflows that create seamless delivery of evidence synthesis support and yield quality service. The paper provides decisions that university libraries must consider as they are planning the implementation of these services. The research-intensive nature of evidence synthesis projects provides liaison librarians with a perfect entry to deliver high-quality and relevant services, especially to graduate students and researchers. Through this work, libraries will demonstrate strong evidence for their engagement and contributions to research on campus. Librarians interested in supporting this latest type of research can use this study to gain a sense of where their own professional strengths fit within this new functional area and plan how to enter this developing research space. This study may be of interest to administrators, reference and instruction librarians, and librarians serving graduate students. Issues are presented in a way that surfaces difficult topics, which will help guide planning conversations between supervisors and librarians regarding workload assignments.

Numerous prediction models of SARS-CoV-2 pandemic were proposed in the past. Unknown parameters of these models are often estimated based on observational data. However, lag in case-reporting, changing testing policy or incompleteness of data lead to biased estimates. Moreover, parametrization is time-dependent due to changing age-structures, emerging virus variants, non-pharmaceutical interventions, and vaccination programs. To cover these aspects, we propose a principled approach to parametrize a SIR-type epidemiologic model by embedding it as a hidden layer into an input-output non-linear dynamical system (IO-NLDS). Observable data are coupled to hidden states of the model by appropriate data models considering possible biases of the data. This includes data issues such as known delays or biases in reporting. We estimate model parameters including their time-dependence by a Bayesian knowledge synthesis process considering parameter ranges derived from external studies as prior information. We applied this approach on a specific SIR-type model and data of Germany and Saxony demonstrating good prediction performances. Our approach can estimate and compare the relative effectiveness of non-pharmaceutical interventions and provide scenarios of the future course of the epidemic under specified conditions. It can be translated to other data sets, i.e., other countries and other SIR-type models.