This International Research Scientist Development Award (IRSDA) from Rhode Island Hospital and Partners In Health-Peru will serve as a vehicle for the candidate, a pediatrician with advanced training in tuberculosis (TB), to become an independent physician-scientist in global health research. The candidate?s long-term goal is to improve outcomes for adolescents with TB by building an adolescent TB clinical research program in Peru. Of note, TB is one of Peru?s six national priority areas for biomedical research. This IRSDA will address the lack of evidence on adolescent-specific risk factors for poor TB treatment adherence. The three specific aims of this study will culminate in the derivation and validation of a clinically applicable prediction rule that identifies adolescents at risk for poor adherence to therapy for drug-susceptible pulmonary TB. Poor adherence will be defined as failure to complete the six-month regimen within nine months. The two parts of Aim 1 will lead to the development of a data collection tool to capture predictors of adherence.
In Aim 1 a, the research team will conduct 70 in-depth interviews with adolescents, parents, and health providers to explore perspectives on barriers and facilitators to adolescent adherence to TB treatment.
In Aim 1 b, the candidate, informed by these interviews, will develop a two-part data collection tool?consisting of a 20- minute structured survey and a brief chart abstraction from?that captures predictors of adherence.
In Aim 2, the research team will administer the data collection tool to 400 adolescents who recently completed or defaulted from TB therapy. Using these data, the candidate will apply regression analysis to derive a clinical prediction rule for poor adherence, and then derive a second prediction rule using recursive partitioning.
In Aim 3, these prediction rules will be externally validated in a prospective cohort of 400 newly diagnosed adolescents. The area under the receiver operator curve for each model will be measured against the outcome of poor adherence, which will be assessed at the end of therapy. The more accurate rule will be selected as the final model and will be incorporated into the candidate?s R01 proposal?which she will prepare in Years 4 and 5 of this IRSDA?to develop novel approaches to optimize adolescent adherence to therapy for TB disease. In parallel with this research plan, the candidate will take courses in epidemiology, biostatistics, clinical prediction modeling, adolescent health, advanced qualitative analysis, the conduct of international clinical translational research, and grant writing. She will also receive instruction in these areas from an experienced mentorship team. Dr. Jennifer Friedman (primary mentor) has 20 years? experience conducting NIH-funded international pediatric infectious disease studies and has successfully mentored previous K recipients. Drs. Leonid Lecca (overseas mentor) and Mercedes Becerra (co-mentor) have a combined 35 years? experience conducting patient-oriented TB research in Lima. Drs. Tao Liu and Jeffrey Starke (advisors) bring expertise in clinical decision modeling and clinical management of pediatric TB, respectively.
Adolescents, who comprise a significant portion of tuberculosis (TB) cases globally, have demonstrated poor TB treatment adherence?which has dire consequences not only for the patients themselves but also for individuals to whom they may transmit the infection. Despite this public health problem, no published studies have examined adolescent-specific predictors of adherence to TB therapy. The proposed research?which will take place in Peru?aims to develop a clinical prediction rule to identify adolescents at risk of poor TB treatment adherence, thus paving the way for targeted interventions to mitigate modifiable risk factors. !
