Capacity Building Activities for Essential Medicines: Beware Unintended Consequences

In Global Perspectives, Expanding medicines for neurological disorders on the WHO Model List, Rimmer and colleagues successfully argue that treatments for neurologic conditions are under-represented in the Essential Medicines List (EML) compiled by WHO each year relative to burden and evidence base for treatment. They conclude that “The low rate of Essential Medicines List inclusion for neurological medications is likely influenced by a relative paucity of application submissions and inadequate neurological or neuropharmacological expertise on the Expert Committee.” They provide details on how application can be submitted, but what individuals or entities should take the lead? And how can applications receive an adequate review of the ‘Expert Committee’ doesn’t include adequate representation from neurologists?

As detailed by Rimmer and colleagues, treatment for neurologic disorders are undoubtedly neglected today in terms of the Essential Medicines Lists (EML) used globally and the reasons for this are complex. In Global Perspectives, they successfully argue that treatments for neurologic conditions are under-represented in the EML compiled by WHO each year relative to burden and evidence base for treatment. They conclude that “The low rate of Essential Medicines List inclusion for neurological medications is likely influenced by a relative paucity of application submissions and inadequate neurological or neuropharmacological expertise on the Expert Committee.” They provide details on how application can be submitted, but what individuals or entities should take the lead? And how can applications receive an adequate review of the ‘Expert Committee’ doesn’t include adequate representation from neurologists? The openness of the process of applying for a medication to be added to the EML, which allows virtually any individual or entity to make an application to the World Health Organization for a drug to be included in the EML, has the downside of not clearly delineating whose responsibility it is to do this. Dr. Rimmer’s paper can be viewed as a “call to arms” for neurologists working in and engaged with activities in resource-limited settings to organize themselves into action to begin to prepare appropriate applications to WHO to improve the situation.

This is clearly a timely topic. A Lancet Commission on Essential Medicines for Universal Health coverage offers additional insights into the problems of an EML that provides care for all1. A concerned word of caution though to urge those who take up the Commission’s advice to be aware of the risk of unintended consequences.

Epilepsy is among the commonest chronic neurologic conditions globally2. In 2006, the World Bank ranked epilepsy among the most cost effective conditions to treat3. Phenobarbitone, a medication on virtually all Essential Medicines Lists, is an inexpensive, easy-to-use, effective antiepileptic drug4—or at least it was until WHO capacity building activities with Pharmaceutical Regulatory Authorities in LMICs led to enhanced requirements for handling controlled substances. Despite a clinical profile making it highly unlikely to be a drug of abuse, the chemical structure of phenobarbitone is such that it falls under the regulatory conditions imposed for controlled drugs. As a result, the handling of phenobarbitone has become costly in terms of personnel time, the requirement to have special locked facilities to secure the drug, documentation of drug distribution and maintenance of this documentation in case of audit. Given the low profit margin of this cheap drug as well as the potential of significant fines and even criminal prosecution one might be exposed to for failing to adhere to the regulations, many pharmacists in LMICS have simply stopped carrying phenobarbitone. Even management of it within the public health sector has been abdicated by many primary care facilities to higher levels of care5. Attempts to get phenobarbitone removed from the list of controlled substances have been ineffective6.

Phenobarbitone is not an isolated example. During a study of antiretroviral (ARV) adherence 7,8, we identified poorer adherence in one catchment and discovered the pharmacies serving this area were providing only 1-2 weeks’ supply of ARVs at a time rather than dispensing the 2-3 months’ supply prescribed. Paradoxically, this problem arose only from pharmacies that had participated in capacity building activities that included additional training of persons responsible for drug purchasing. The take home message from the training was that the purchaser’s responsibility was to assure that drugs did not run out of stock AND drugs did not expire on the shelf. Giving shorter courses of ARVs helped assure that the drug purchasers met job performance evaluations, but clearly the overall outcome here was not as intended. In pursuing the Commission’s recommendations and as neurologist globally contemplate efforts to expand the EMLs to better cover neurologic needs, unexpected consequences need to be anticipated and evidence for them actively sought. And mid-stream policy changes need to be made when negative effects are identified.

References

  1. Wirtz VJ, Hogerzeil HV, Gray AL, et al. Essential medicines for universal health coverage. Lancet 2017; 389(10067): 403-76.
  2. WHO. EpilepsyUpdated Feb 2017, 2017. http://www.who.int/mediacentre/factsheets/fs999/en/ (accessed 14Feb17).
  3. World Bank. Disease Control Priorities in Developing Countries. New York, NY: Oxford University Press & THe World Bank; 2006.
  4. Brodie MJ, Kwan P. Current position of phenobarbital in epilepsy and its future. Epilepsia 2012; 53 Suppl 8: 40-6.
  5. Chomba EN, Haworth A, Mbewe E, et al. The current availability of antiepileptic drugs in Zambia: implications for the ILAE/WHO “out of the shadows” campaign. Am J Trop Med Hyg 2010; 83(3): 571-4.
  6. Bhalla D, Aziz H, Bergen D, et al. Undue regulatory control on phenobarbital–an important yet overlooked reason for the epilepsy treatment gap. Epilepsia 2015; 56(4): 659-62.
  7. Birbeck GL, Chomba E, Kvalsund M, et al. Antiretroviral adherence in rural Zambia: the first year of treatment availability. Am J Trop Med Hyg 2009; 80(4): 669-74.
  8. Birbeck GL, Kvalsund MP, Byers PA, et al. Neuropsychiatric and socioeconomic status impact antiretroviral adherence and mortality in rural Zambia. Am J Trop Med Hyg 2011; 85(4): 782-9.
Gretchen L. Birbeck, MD, MPH

Gretchen L. Birbeck, MD, MPH

Gretchen Birbeck is a neurologist who divides her time between the US and Africa. Her US academic home is the University of Rochester where she is the Rykenboer Professor of Neurology and Research Director for the Strong Epilepsy Center with adjunct appointments in the Center for Human Experimental Therapeutics and the Department of Public Health. Her additional skills in epidemiology, health services research, and tropical medicine are brought to bear during the 6-months annually she spends in Africa where she serves as Director for the Chikankata Epilepsy Care Team in rural Mazabuka, Zambia, an Honorary Lecturer at the University of Zambia and a consultant for the Paediatric Research Ward at Queen Elizabeth Central Hospital in Blantyre, Malawi. Gretchen’s research programs are aimed at identifying opportunities to prevent or ameliorate the medical and social morbidities of common neurologic conditions in low-income, tropical settings with the ultimate goal of developing successful interventions feasible for scale up and broad implementation. She has been recognized as an Ambassador for Epilepsy by the International League against Epilepsy, a Global Health Research Ambassador by the US Paul Rogers Society, a National Outreach Scholar by the WK Kellogg Foundation and a Leader in Medicine by the American Medical Students Association.

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