4.6 Monitoring and evaluation

Patients who receive BPaL (or any shorter regimen for the treatment of MDR/RR-TB) need to be tested at baseline and then monitored during treatment using schedules of relevant clinical and laboratory testing. According to the product label of pretomanid, baseline assessments before initiation of the BPaL regimen include assessments for symptoms and signs of liver disease (e.g. fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness and hepatomegaly) and the conduct of laboratory tests such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and bilirubin, complete blood count and serum potassium, calcium and magnesium (which should be corrected if abnormal). Treating clinicians should also obtain an ECG before initiation of treatment. The baseline monitoring schedule of the Nix-TB study was much more comprehensive than this; it included a thorough baseline clinical assessment, then a schedule of weekly patient monitoring until week 20, followed by 4–6 weekly monitoring, partly dependent on whether the patient had treatment for 6 months in total or 9 months in total.

Given that the BPaL regimen is new and is being implemented under operational research conditions, it is also important to follow up patients after the completion of treatment for possible relapse. In the Nix-TB study, monitoring after the completion of treatment was carried out monthly for months 1–3, and 3-monthly thereafter. Follow-up after treatment completion was for a total of 24 months; however, at the time of data analysis, about half of the patients had been followed up for this period. The analysis of the Nix-TB study data indicated that treatment failure or recurrence occurred in three patients (2.8% of patients overall), taking into account the period of post-treatment completion follow-up.

Detailed schedules of baseline and follow-up monitoring, including post-treatment completion, should be developed for any BPaL operational research protocol, with standardized measures for recording adverse events. A suggested schedule of monitoring is provided in the WHO operational handbook on tuberculosis. The WHO framework for aDSM needs to be applied to patients on any type of MDR-TB regimen, to ensure appropriate action and an acceptable level of monitoring for and prompt response to adverse events – alongside monitoring for treatment outcomes, including early monitoring for treatment failure. Additional evidence generated on adverse events will be important to build the evidence base on the safety of the BPaL regimen in varied settings.

Monitoring of changes in dosing and duration of linezolid in particular (when needed) will also be important, to inform the future evidence base on the wider use of the BPaL regimen and the tolerability of linezolid in this regimen.  

Book navigation