Transcript Trials and evidence in relation to health policy: The

Trials and evidence in relation to
health policy: The case of
tuberculosis in Nepal and India
Ian Harper
Rifampicin
Overview of presentation
• Rifampicin, and its history in TB control
• Regulation
– DOTS
– Procurement for NTPs
• Relations between the private sector and
NTP (India and Nepal)
• Conclusion
Summary of TB treatment in the
pharmaceutical era
• Monotherapy doesn’t work, and treatment has
to be a combination of chemotherapy agents
• The discovery and production of rifampicin key
in bringing TB out of the sanitorium and the
development of ambulatory treatment.
• Length of treatment means the question of
adherence is crucial
Drugs currently used for TB treatment
FIRST LINE DRUGS
• Isoniazid (H)
• Rifampicin (R)
• Ethambutol (E)
• Pyrazinamide (Z)
• Streptomycin (S)
SECOND LINE DRUGS
• Kanamycin (KM)
• Amikacin (AMK)
• Capreomycin (CM)
• Quinolones (FQ) – Cipro, Ofx, Gfz, Mfx
• Ethionamide or Prothionamide (Thiamides)
• Cycloserine (CS) or Terizdone (Tzd).
• Para-aminosalicylic Acid (PAS)
Current Treatment
recommendations (first line)
• Treatment based on the idea of a “intensive
phase” (IP) and then “continuation phase” (CP)
• At least two bacteriacidal drugs in the IP. Adding
pyrazinamide decreases overall treatment to 6
months
• CP mops up residual bacilli and results in less
likelihood of relapse
Drug Resistance
• MDR defined as resistance to at least
rifampicin and isoniazid
• Rifampicin key to the debate, and has to
be “protected” (including):
– Limit availability to national regimes
– Make it only available in FDCs
– Observation of patients taking drugs
India and Nepal’s national regimes
• India has an intermittently administered regime
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(3x per week)
Nepal has daily therapy (and till 4 months ago)
had no rifampicin in the continuation phase
Each has three categories of treatment (i, ii, iii)
Each must have a “directly observed”
component (rephrased in 2006 as “patient
support”)
Why intermittent therapy? (India)
• DOT seen as an absolute must for
rifampicin based combinations
• Logic is that it is therefore easier on the
patients to have this only three times per
week, rather than daily
• Cost
Evidence base?
• Friedman (2004) in a review suggests that
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intermittent therapy is as good as daily, and that
animal model experiments suggest there is an
increase in efficacy of HRZ, and is “perhaps
slightly more effective than the daily regime”
Cochrane (2005) argue no evidence to support
assertions that IR is better than daily (need
more research)
Why eight month regime? (Nepal)
• WHO and IUATLD don’t like rifampicin through
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whole regime (“protect the rifampicin”)
Less likely to get rifampicin resistance should
patients relapse
Claims of less DOT burden on the patient (two
months rather than six)
Cost
• (NB Nepal’s regime changed in Dec 2008 to
rifampicin based in the continuation phase)
Methods
• Interviews with prescribers (chest
physicians and GPs)
• Interviews and visits to DOTS clinics, and
government officials
• Interviews with retailers etc.
• Interviews with company representatives
(Nepal, West Bengal, Delhi and UP)
Perceptions of the regime and
DOTS (prescribers)
Very inconvenient for patients
Too cumbersome and rigid in implementation (e.g.
not good for migrants)
DOTS only for poor patients, and not the best
Intermittent regime based on costs, not science:
India is a “poor” country
Not enough dosage flexibility
Category 2 is adding one drug to a “failing regime”
and contradicts WHO’s own policy
DOTS policy based on “irrational optimism”
Don’t know MDR levels, regime may be wrong and
feeding further resistance (India)
Free drugs a bad idea- people don’t take it
seriously
Perception that the WHO and the NTP don’t listen
Why private sector better?
(self perceptions)
• Flexibility on dose and weight schedules
• Regime too short
• Easier on patients (no DOT), “why go the
clinic when you could go to work”?
• Accountability
• Poor performance and quality of the
government system; lack of trust
• Trust in certain company products (Lupin
in particular)
In Nepal…
• Widespread resistance to the national
regime because no rifampicin in the CP
• Greater flexibility for patients
• Distrust of the claims made by the NTP
Differences between Nepal and
India
• Scale
• DOTS in Nepal much more widely known
• Nepal: Reports of decreased sales of TB drugs from
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retailers (e.g. where there are well functioning DOTS
clinics)
Major Indian TB drug producers dominate the Nepal
market (Lupin, MacLeods, Concept, Cadilla)
As such rifampicin now mainly available as either FDCs or
is “strip” packs
Complaints by prescribers of lack of availability of
uncombined rifampicin on the market (eg Paediatric
formulations)
Criticisms of each regime are technical and specific to
each
Discussion points
• Don’t ignore the perceptions of private
practitioners, because
– They confirm the lack of flexibility of DOTS and its
failure to respond to patient needs
– They adapt to patient demands
– BUT variability of treatments a problem
– Never sure what the financial incentives are
• DOTS must be more flexible AND consistent