Evidence-based medicine in low-income and middle-income countries
Authors: Sudeep Adhikari
Journal: The Lancet Global Health (2021)

Evidence-based medicine is the backbone of modern medicine. Any newly proposed therapy needs to be tested in high-quality randomised controlled trials (RCTs) before being considered for approval. Nepal is a low-income country in south Asia. Researchers in Nepal have been contributing to global health by doing RCTs in high-altitude medicine and infectious diseases like typhoid. Infectious diseases such as tuberculosis, typhus, and leptospirosis, and non-infectious diseases such as hypertension, diabetes, atherosclerotic diseases, cancers, liver diseases, kidney diseases, and autoimmune diseases are also present in Nepal. However, so far, no high-quality studies have been done in patients with these diseases in the country. Thus, clinicians manage these diseases as per international guidelines that are based on studies from other populations—usually from high-income countries—but with modifications based on their experiences and expertise, rather on the findings of local RCTs. Most drugs have weight-based dosing. The average weight of adults in low-income and middle-income countries is lower than that in of adults in high-income countries.1Walpole SC Prieto-Merino D Edwards P Cleland J Stevens G Roberts I The weight of nations: an estimation of adult human biomass.BMC Public Health. 2012; 12: 1-6Crossref PubMed Scopus (410) Google Scholar Doctors in Nepal hypothesise that this weight difference might be why patients often do not tolerate the guideline-recommended doses of many drugs. As a result, doctors tend to prescribe drugs in lower doses than recommended. For example, in patients with cirrhosis and ascites, furosemide is commenced at 40 mg and spironolactone at 100 mg, with maximum limits of 160 mg for furosemide and 400 mg for spironolactone.2Runyon BA Introduction to the revised American Association for the Study of Liver Diseases practice guideline management of adult patients with ascites due to cirrhosis 2012.Hepatology. 2013; 57: 1651-1653Crossref PubMed Scopus (453) Google Scholar Nepalese patients can develop electrolyte disturbances at these doses; thus, furosemide is often started at 20 mg and spironolactone at 50 mg. In my experience, no patients have tolerated up to the maximum limits of these drugs. The usual recommended dose of intravenous pulse methylprednisolone in most autoimmune disease flares is 500–1000 mg once a day.3Sinha A Bagga A Pulse steroid therapy.Indian J Pediatr. 2008; 75: 1057-1066Crossref PubMed Scopus (67) Google Scholar In low-income and middle-income countries, clinicians are sceptical of prescribing the drug at this dose because, in addition to low body weight, a fear of hidden infection like tuberculosis remains. Hence, a dose range of 250–500 mg is preferred. Patients with atrial fibrillation need to be on oral anticoagulants to prevent stroke. International guidelines4January CT Wann LS Calkins H et al.2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines and the Heart Rhythm Society.J Am Coll Cardiol. 2019; 74: 104-132Crossref PubMed Scopus (669) Google Scholar now recommend direct oral anticoagulants over warfarin because the risk of life-threatening bleeding is lower and the coagulation profile does not need to be monitored. However, direct oral anticoagulants are expensive for patients in low-income and middle-income countries like Nepal. In contrast, warfarin, which is cheaper than direct oral anticoagulants, introduces substantial risk for patients living in mountainous and remote places, because regular monitoring of their coagulation profile is almost impossible. Without regular monitoring, these patients can end up in hospital with life-threatening bleeding. With this fear in mind, most patients undergoing atrial fibrillation in Nepal receive the antiplatelet agent aspirin alone. The south Asian population is now known to be at higher risk of atherosclerotic cardiovascular diseases even at a lower body-mass index than populations in high-income countries. Hence the body-mass index cutoff for overweight and obesity has been modified for the south Asian population. About 150 min of brisk walking per week is recommended in patients with atherosclerotic cardiovascular diseases,5Volgman AS Palaniappan LS Aggarwal NT et al.Atherosclerotic cardiovascular disease in south Asians in the United States: epidemiology, risk factors, and treatments: a scientific statement from the American Heart Association.Circulation. 2018; 138: e1-e34Crossref PubMed Scopus (124) Google Scholar but for most such patients in Nepal, who live in mountainous regions, their normal weekly activity far exceeds this recommendation. This disconnect indicates a need for further studies regarding evaluation and management of atherosclerotic cardiovascular diseases in south Asia. Such local studies could provide more specific lifestyle recommendations for these patients. High patient burden per doctor, poor technological advancement, poor data recording, insufficiency of funding or grants, and an absence of research-friendly government or institutional policies are all factors that have contributed to a poor research culture in low-income and middle-income countries. Additionally, researchers in these countries might not be able to afford the required article processing charges to publish in Open Access, high impact factor journals, or be unaware of the option to request a fee waiver. As a result, local researchers and experts get little international recognition, and are not invited by international professional communities during preparation of clinical guidelines, which means their experience and expertise are not usually represented in the international guidelines. Funders and researchers from high-income countries should focus on research activities in low-income and middle-income countries involving the local researchers. Promoting a positive research culture should be the first step to improve global health in low-income and middle-income countries, so that the people living in these countries can truly benefit from evidence-based medicine and health services. I declare no competing interests.