Trials and evidence in relation to health policy: The case of tuberculosis in Nepal and India

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Trials and evidence in relation to health policy
The case of tuberculosis in Nepal and India

• Ian Harper

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Rifampicin
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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

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Summary of TB treatment in the pharmaceutical era

• Monotherapy doesnt 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

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• 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)

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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

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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

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India and Nepals national regimes

• India has an intermittently administered regime
  (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)

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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

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Evidence base?

• Friedman (2004) in a review suggests that
  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)

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Why eight month regime? (Nepal)

• WHO and IUATLD dont like rifampicin through
  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 Nepals regime changed in Dec 2008 to
  rifampicin based in the continuation phase)

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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)

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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

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• Category 2 is adding one drug to a failing
  regime and contradicts WHOs own policy
• DOTS policy based on irrational optimism
• Dont know MDR levels, regime may be wrong and
  feeding further resistance (India)
• Free drugs a bad idea- people dont take it
  seriously
• Perception that the WHO and the NTP dont listen
  to their concerns and take them seriously

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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)

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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

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Differences between Nepal and India

• Scale
• DOTS in Nepal much more widely known
• Nepal Reports of decreased sales of TB drugs
  from 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

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Discussion points

• Dont 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