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Synopsis of the Literature Review for WG 7:

Evidence Base

 

The Clinical and Epidemiological Evidence Base of Seven Tracer Medicines in Three Low- to Middle-income Countries.

The AMASA project seeks to unravel the complex pharmaceutical supply chain in three focus countries – India, Uganda and South Africa – by tracing seven medicines in diverse health care areas. Although the main objective of the project is to establish the production/acquisition, regulation, funding, distribution and community involvement in the supply chain, establishing the background evidence base of each of these medicines in order to place it in a larger international public health context is crucial. Working Group 7 (WG7) critically examined the literature to draft a comprehensive background document on each of these medicines within a public health context, both from an international perspective and that of each focus countries.

Tracer medicines:

The selected tracer medicines are Rifampicin to treat tuberculosis, Lamivudine to treat HIV/AIDS, Oxytocin to treat postpartum haemorrhage, Fluoxetine to treat mental health conditions, Artemisinin to treat malaria, Metformin to treat type II diabetes, and Fentanyl to treat chronic pain. Oxytocin, Rifampicin and Fluoxetine were selected as they follow previous research conducted in India and Nepal within the Tracing Pharmaceuticals in South Asia (TPSA) project conducted at the University of Edinburgh. All seven medicines play important roles in key health areas: maternal health, infectious disease control, mental health, palliative care and chronic disease which allow for contrasting insights into various aspects of the pharmaceutical supply chain from a variety of health care perspectives.

Key questions:

These reviews on the evidence base for each of the seven tracer medicines seek to answer the following key questions: what is the evidence base in support of the use of each of these selected medicines, what is the epidemiological evidence underpinning disease priority (and/or Global Burden of Disease), what are the international and local guidelines for use and what is the evidence regarding unmet need and off-label use for each medicine. Important as well is to investigate the existence of substandard or counterfeit versions of our tracer medicines and their involvement in the local pharmaceutical supply chain. A short background on each of the seven tracer medicines:

Oxytocin

Oxytosin is used to induce and support labour in cases of non-progression as well as for prevention and treatment of postpartum haemorrhage. It should only be administered in hospital conditions, usually through an intravenous route, and its effects continuously and closely monitored by qualified health professionals. By contrast, in South Asia, Oxytocin is routinely used by intramuscular injection, with likely public health implications, as reported during the TPSA study. High and growing levels of Oxytocin use have major implications for the WHO Safe Motherhood programme.

Rifampicin

Rifampicin, a bacteriocidal agent used in combination with other drugs to treat tuberculosis (TB), and central to WHO’s global treatment policy, Directly Observed Therapy (DOTS). Rifampicin thus forms an integral part of the international donor economy, but this tends to mask the significance of private sector supply chains, even where DOTS programmes are free to patients at the point of contact. National TB control programmes often receive funds from the World Bank, USAID, DfID, and GFATM, to name a few. It is crucial to gain a more thorough understanding of the role that the drug delivery system, including the funding, dispensing and administration of these drugs, plays in facilitating TB control programmes, especially with an increased spread of multidrug-resistant TB.

Fluoxetine

Fluoxetine is used in the treatment of depression, which the WHO has predicted will be the second most common worldwide affliction (after cardiovascular diseases) by 2020. Fluoxetine is probably the most widely used selective serotonin reuptake inhibitors (SSRI) and was first introduced by Eli Lilly under the brand name Prozac. It has been off-patent since 2001 resulting in most Fluoxetine drugs being produced generically with Indian companies dominating some African and other South Asian markets. Although mental health has a large disease burden with a recognised treatment gap, almost nothing is known about the patterns of fluoxetine use, levels of consumption, or their effects on the population.

Antiretrovirals

Antiretrovirals (ARVs) entail three main classes of drugs – nucleoside/nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors, and protease inhibitors – although research is ongoing to produce new classes of drugs such as fusion inhibitors. ARVs used in the treatment of HIV are typically prescribed in combination and are becoming more and more available as fixed-dose combinations (FDCs). The WHO Essential Medicines Committee designates fixed-dose combinations of drugs from these respective classes, and recommends and endorses the use of this approach to treatment. Lamivudine (or 3TC) is an NRTI which is used as one of the drugs in a triple-combination therapy which is recommended to treat HIV infection in each of our focus countries.

Artemisinin

Artemisinin, originally a herbal remedy, is currently the most successful treatment for falciparum and cerebral malaria in much of Africa. It is recommended as an artemisinin-based combination therapy (ACT) but, as the mono-therapy form is cheaper and readily available, patients commonly choose this treatment regimen over ACT. There are huge repercussions from the overuse of Artemisinin as a mono-therapy which prompted the WHO in 2006 to call an end to the production and marketing of Artemisinin mono-therapies in order to protect these formulations from resistance. The limited diagnostic testing in resource-poor countries can also contribute to the resistance of Artemisinin. Furthermore, the high persistence of substandard or fake drugs and clinically inappropriate mono-therapies in the private sector poses a risk to patient safety and increases drug resistance, placing future global malaria treatment at risk.

Fentanyl

Fentanyl is a narcotic analgesic nearly 100 times stronger than morphine and is used most commonly in palliative care for severe and/or chronic pain associated with cancer and HIV/AIDS or as a surgical anaesthetic. In either case, it can be taken as a monotherapy or in combination with other narcotics or anaesthetics and can be administered intravenously or, more recently, as a transdermal patch. Fentanyl is not on the WHO’s Essential Medicines List. Tracing this medicine through the pharmaceutical supply chain provides an opportunity to investigate the involvement of palliative care programming in our focus countries.

Metformin

Metformin is recommended as a first line treatment for patients with type 2 diabetes when diet and exercise have not achieved glycaemic control. It is one of the most widely prescribed oral anti-diabetic medications in the world and is available as a combination drug with other oral anti-diabetic medications or other drug classes such as statins. It is also used in pregnancy for both pre-existing and gestational diabetes or as an unlicensed indication for the symptomatic management of polycystic ovary syndrome. Metformin is one of two oral antidiabetic drugs in the WHO Essential Medicines list and provides an opportunity to follow treatment patterns for an increasingly prevalent chronic disease.

Conclusion

These literature reviews provide a plethora of background information on each selected medication and associated condition in the global, as well as the local context. Other working groups within the AMASA project can rely on these reviews as they investigate the complex pharmaceutical supply chain for each individual tracer medicine within their specific topic area.

 

This synopsis is a result of the collaboration within WG7, under the coordination of the WG7 coordinators: Allyson Pollock and Valerie Evans.

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