Table 1.

Possible Poor Treatment Response Triggers and Evaluation Procedures

Standardized PPTR Triggers	Standardized PPTR Evaluation Procedures
PPTR triggers driven by microbiological and clinical data	1.Review of participant personal contact information 2.Review of adverse events and interval medical history 3.Symptom assessment 4.Concomitant medication assessment 5.Measurement of weight 6.Chest radiograph 7.At least THREE (3) SPUTA should be collected within 1 week. At least TWO of these sputa should be collected before changing or restarting TB treatment, and at least 4 h apart. At least ONE sputum should be a first morning specimen, if feasible. These sputa should be sent to the study laboratory for smear and culture. If M. tuberculosis is isolated in culture, drug susceptibility testing should be performed on one of the isolates. Then the isolate from each positive culture should be stored frozen 8.For participants consenting to collection of specimens for identification of potential biomarkers of TB treatment response: sputum, urine, and blood specimens should be obtained 9.Contact the central study clinician when PPTR evaluation is initiated and ideally before changing or restarting TB treatment* 10.Complete the PPTR case report form
Culture of sputum obtained at or after Week 17 is positive for Mycobacterium tuberculosis
Smear microscopy of sputum obtained at or after Week 17 is positive for acid-fast bacilli
Worsening signs or symptoms compatible with TB at or after Week 17
Radiographic worsening compatible with TB at or after Week 17
Treatment change PPTR triggers
Site investigator is considering an extension of TB treatment beyond that of the participant’s assigned regimen
Site investigator is considering reinitiating any TB treatment after the participant has completed assigned study treatment
Site investigator is considering a change in treatment for efficacy reasons (this does not apply to changes in treatment due to pregnancy or drug toxicity or to temporary drug rechallenge)

Definition of abbreviations: PPTR = possible poor treatment response; TB = tuberculosis.

If a participant experienced any of the PPTR triggers, then all of the PPTR evaluation procedures should have been implemented regardless of treatment assignment.

^*The central study clinician was blinded to participant treatment assignment. The purpose of this communication was to review the PPTR procedures and ensure adherence with them.