The TuberXpert project protocol: Towards a Clinical Decision Support System for therapeutic anti-tuberculosis medical drugs monitoring in Tanzania

IntroductionThe End Tuberculosis (TB) Strategy requires a novel patient treatment approach contrary to the "one-size fits all" model. It is well known that each patients physiology is different and leads to various rates of drug elimination. Therapeutic Drug Monitoring (TDM) offers a way to manage drug dosage adaptation but requires trained pharmacologists, which is scarce in resource-limited settings. We, therefore, aim to create an unprecedented Clinical Decision Support System (CDSS) that will offer a printable report containing advice for the field clinicians to guide the adaptation of TB treatment depending on the patient. Methods and analysisA population pharmacokinetic model for rifampicin will be developed and thoroughly validated, before being implemented into Tucuxi, an existing Model Informed Precision Dosing software. A cross-sectional study will be conducted to define the best way to display information to clinicians. In addition, a pragmatic prospective study will focus on a decision tree that will be implemented as a CDSS. Expert pharmacologists will validate the CDSS, and, finally, field implementation in Tanzania will occur coupled with a prospective study to assess clinicians adherence to the CDSS recommendations. Ethics and disseminationThis is a game-changing transdisciplinary project combining technology and pharmacometrics to enable appropriate dosages of anti-TB drugs in TB patients at various levels of the healthcare delivery system in TB-endemic settings. The project is part of the Adaptive Diseases control Expert Programme in Tanzania, which has been approved at the local health research committee serving Kibongoto Infectious Diseases Hospital (KIDH) and National Health Research Committee with reference numbers KNCHREC003 and NIMR/HQ/R.8a/Vol.IX/2988, respectively. Furthermore, the Ministries of Health and Regional Administrative & Local Government Authority have endorsed the implementation of this protocol. Dissemination will be done through scientific publications, conferences, and local press in Tanzania. Social media will also be used to gain more visibility. Strengths and limitations of this study- To our knowledge, this is the first study to investigate the application of CDSS technology at varying healthcare delivery systems levels to guide TDM in TB patients in TB-endemic settings. - Routine implementation of TDM-CDSS, particularly for rifampicin, a backbone for TB treatment, is expected to transform TBs clinical management in resource-limited settings. - Anti-TB dosage optimization will improve treatment outcomes of patients who would otherwise succumb or develop drug-resistant TB because of sub-optimal drug exposure. This will considerably contribute to the End TB strategy, particularly with arduous forms of TB with either Human Immunodeficiency Virus (HIV) co-infection or coexistent Diabetes Mellitus (DM) or malnutrition. - Clinicians could also use the CDSS decision tree without access to IT infrastructure. - A lack of computer infrastructure in health facilities may prevent implementing a centralized system in resource-limited countries.