17.2 Definitions of treatment outcomes


For all forms of TB, outcome definitions have many similarities. These are:
– Outcome assignment is standardized, as to permit comparisons across clinicians, time and sites.
– Outcome assignment relies heavily, but not exclusively, on bacteriologic endpoints (smear or culture1 ).
– Outcomes are mutually exclusive and exhaustive.

For all forms of TB, definitions exist for:
– Interim outcomes (intended to have an indication on how the programme is functioning before final outcomes are available);
– Final outcomes (cure, completion, failure, treatment interruption, death or not evaluated).

17.2.1 Interim outcomes for drug-susceptible TB and MDR-TB

Given that TB treatment is long (6 to 18 months or more), interim outcomes provide early indicators of programme results. Table 17.1 provides a summary on interim outcomes.

Table 17.1 - Interim outcomes

TB

Interim outcomes

Drug-susceptible TB

At 2-3 and 4-5 months:
• Bacteriological status (smear negative/positive/no information)
• Final outcomes in patient who had already interrupted or died

MDR-TB

At 6 months:
• Bacteriological status (negative/positive/no information) based on smear and culture
• Final outcomes in patient who had already interrupted or died

17.2.2 Final outcomes for drug-susceptible TB and DR-TB

Table 17.2 provides definitions for the final outcomes.

Table 17.2 - Summary table of final outcome definitions1,2

Outcomes

TB

Definitions


Cured


DS TB

Patient initially bacteriologically confirmed (microscopy, culture or molecular test) who completed treatment
AND shows no signs of continued active disease
AND has at least 2 negative smears or cultures: one at 4-5 months and the other at the end of treatment
AND does not meet the definition of failure.


PDR-TB

Patient initially bacteriologically confirmed (culture or molecular test), who completed treatment
AND has been consistently culture-negative with at  least 3 results on sputum tested at least one month apart for the final 6 months of treatment
AND does not meet the definition of failure.



MDR-TB

Patient initially bacteriologically confirmed (culture or molecular test), who completed treatment
AND with at least 3 negative cultures in the last 8 months of treatment
AND does not meet the definition of failure.

If there is a lone positive culture or smear reported during that time, and no concomitant clinical evidence of deterioration, a patient may still be considered cured, provided that this positive culture is followed by a minimum of 3 consecutive negative cultures taken at least 30 days apart.


Completed


All

Patient who completed treatment
AND has no signs of continued active disease
AND does not meet the bacteriological criteria for cure.




Failure



DS TB

Patient with signs of continued active disease or deterioration requiring a treatment change:
• Any patient with positive smear or culture at 4-5 months of treatment or thereafter.
• Any patient with no significant clinical improvement, no significant gain of weight after 4-5 months of treatment and for whom the diagnosis of failure is established by a clinician.



DR-TBa,b,c

Treatment terminated or need for permanent treatment change of at least 2 classes of anti-TB drugs because of one or more of the following:
• Lack of monitoring cultures converting to  negative by  6 months for MDR-TB (3 months for PDR-TB), and/or
• Resistance amplification to rifampicin or isoniazid (PDR-TB) or to Group 2 or Group 3 drugs (MDR-TB), and/or
• Bacteriological reversion (at least two positive smears or cultures at least 7 days apart after monitoring smears or cultures have become negative), or
• A clinical decision has been made to terminate treatment early due to poor response or adverse events. These latter failures can be indicated separately in order to do sub-analysis.

Interrupted All Patient who interrupted treatment for 2 months or more.
Death All Patient who died on TB treatment or while awaiting TB treatment, irrespective of the cause of death. The cause of death should be recorded.
Treatment adaptedd,e DS TB Patient initially treated with a standard regimen and for whom the treatment is secondarily adapted according to the results of DST (and not because of a treatment failure).
Not evaluated All Patient whose treatment outcome is unknown (including patients “transferred out” to another treatment centre, for whom the outcome is unknown).

a. A patient registered as “failure” can be re-registered as DR-TB “previously treated 2nd  line” and started again on a new regimen if possible.
b. This category does not include the changing of one drug due to an adverse effect or a temporary cessation of drugs in order to manage severe adverse event.
c. If a patient was defined as a “failure”, and no appropriate treatment was possible, but the treatment was continued and the patient subsequently interrupted the treatment or died, the outcome is “failure” (the first outcome is recorded).
d. For programmes that report using the WHO’s mutually exclusive six outcomes, the “treatment adapted” outcome can be added to failures for reporting purposes, but should also be kept track of separately for good programmatic monitoring and evaluation.
e. Not applicable for DR-TB.

If treatment is continuing at the time of a cohort analysis, an outcome of “still on treatment” may be provisionally assigned



Footnotes
Ref Notes
1

Molecular techniques are not used to monitor treatment response or to declare failure. These tests may identify dead bacilli for a long time and can even be positive after a patient is truly cured.