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Randomized clinical trials (RCT) are an important tool that has led to important reduction of global childhood mortality. Low and middle-income countries (LMICs) still face important challenge in stunting (low height-for-age) that can produce detrimental effects on child’s long-term development. Facing important challenges in stunting Rwanda has adopted stunting prevention with a particular focus on complementary feeding period ([CFP]: 6-24 months) as their national strategic plan. Rapid Pro, a community health workers program that provides routine health and monitoring services from pregnancy to five years of age using SMS, is a unique health system in Rwanda that can be used to improve linear growth for their children. A single overarching master protocol for an adaptive platform trial (APT) that could be embedded into Rapid Pro to determine comparative effectiveness of multi-component interventions on linear growth during CFP was developed. APTs are a new RCT design that allows for evaluation of multiple interventions against a common control using interim evaluation and flexibilities of allowing new interventions to be added during the trial. To inform the trial design, a landscape analysis of master protocols and APTs was done through a systematic literature review (SLR). This showed 83 master protocols, 16 of which were platform trials, that have been mostly conducted in the US (n=44/83) for pharmaceutical development (n=82/83). This was followed by an SLR with network meta-analysis (NMA) of LMIC-based RCTs studying interventions under the domains of micronutrients and food supplements, deworming, maternal education, and water, sanitation, and hygiene aimed to improve linear growth for children during CFP. An NMA of 79 RCTs involving 81,786 children showed largely equivocal results highlighting the need for more investigation with interventions being combined and tested as packages. The results of these findings were then presented to the governmental stakeholders to determine intervention packages to be tested and to inform the APT design. Simulations were performed to design Bayesian early stopping rules that could reduce the expected sample size while keeping type I error rates under 2.5%. The findings support the use of APTs for child health and other key areas in global health research.

Background: Despite the availability of effective therapy, health outcomes are poor and costs associated with asthma are high. Consistent reports of sub-optimal medication adherence among adults with asthma highlight the importance of assessing the effect of interventions on medication adherence and exploring possible mechanisms to better understand how medication adherence can be promoted and supported.Objectives: My objectives are to review the effects of interventions to improve asthma outcomes on medication adherence and to explore the impacts of text message supported interventions on self-reported medication adherence using a mixed methods approach. Methods: For the systematic review, I conducted a search of databases to identify randomized controlled trials of interventions to improve asthma outcomes using medication. A structured framework was applied to classify interventions based on the emphasis placed on medication adherence. Furthermore, I conducted two convergent mixed methods studies integrating qualitative findings with medication adherence results nested within two studies to improve asthma outcomes. Results: 61 RCTs testing interventions to improve asthma outcomes using medication were identified with variable degree of emphasis placed on medication adherence. The systematic review showed that medication adherence can be effectively promoted if it is seen as objective by researchers. However, improvements observed in medication adherence could not be translated into better health outcomes. These contradictory findings could reveal limitations of RCTs to show some effects in clinical epidemiology. Self-reported medication adherence changes observed in the two nested mixed methods studies could be elucidated by differences in their settings as showed by the integration with a patient-centered model that emerged from the interviews with participants.To my knowledge, this is the first investigation that integrates a patient-centered model with self-reported medication adherence to expand our understanding of medication taking behaviours and generate recommendations for future interventions to improve medication adherence in asthma. Conclusion: This thesis shows how inconclusive results of RCTs to test interventions to improve asthma outcomes are not sufficient to provide answers for all questions. The integration of patients’ perspectives into the equation could bring some clarity into the problem and generate possible solutions for the complex phenomenon of medication non-adherence in asthma.

Introduction: The World Health Organization has ambitious goals to eliminate AIDS and TB globally. However, the plan is expensive and financial commitment to achieve this goal is uncertain. Mobile phone-based short message service (SMS) interventions have demonstrated the ability to improve HIV drug therapy adherence. My objective was to evaluate the cost-effectiveness of SMS-based adherence interventions in three settings, which have unique epidemics and health systems, yet struggle with similar adherence barriers. In this thesis, I also consider the value of conducting a cost-effectiveness evaluation before, during and after a randomized trial.Method: This thesis has three parts. First, I evaluated the cost-effectiveness of SMS-based HIV drug adherence interventions in Kenya, where the interventions were first developed. Second, I evaluated the burden of non-adherence and cost sensitivity of SMS-based adherence interventions for latent tuberculosis infection (LTBI) drug therapy in British Columbia, where a trial of an SMS-based adherence intervention is underway. Finally, I evaluated 5,836 combinations of 15 HIV interventions, to understand the role of SMS interventions as part of a combination HIV intervention in India where a trial was being planned. Value was expressed in terms of incremental cost-effectiveness ratios (ICERs), which were a function of incremental costs and quality-adjusted life years (QALYs).Results: In Kenya, the SMS interventions were highly cost-effective in the base case (ICER=$1,389/QALY), and remained cost-effective across most sensitivity analyses. In British Columbia, hypothetical interventions that brought the population to full adherence to LTBI drug therapy could cost up to $450 per person per year and remain cost-effective. SMS interventions were least sensitive to cost and would likely be cost-effective if their efficacy were confirmed. Finally, in India, the SMS interventions were cost saving and were part of 4 of the 5 most efficient combination interventions out of 5,836 possible combinations.Conclusion: The SMS interventions are cost-effective or cost saving when compared to the standard of care in multiple settings. Findings support the implementation of SMS interventions as part of HIV and TB care and suggest they could play an essential role in global containment of these diseases.