Introduction: The End Tuberculosis (TB) Strategy requires a novel patient treatment approach contrary to the "one-size fits all" model. It is well known that each patient's 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 analysis: A 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 dissemination: This 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 Kibong'oto 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.

The authors have declared no competing interest.

This work is funded by the Swiss National Science Foundation, under grant IZSTZ0_208544.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The project is part of the Adaptive Diseases control Expert Programme in Tanzania, which has been approved at the local health research committee serving Kibong'oto Infectious Diseases Hospital (KIDH) and National Health Research Committee with reference numbers KNCHREC003 and NIMR/HQ/R.8a/Vol.IX/2988, respectively.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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This paper presents a project at its beginning, so no data is yet available.