I. Funding bias in medical research
There used to be a time when science was as easy and as accessible (though not all of it) as school lab experiments. Most tools and equipment were fashioned out of available resources and produced one-at-a-time locally. Of course, we are talking about pre-industrialization times. Research is much more expensive now, in major part because of the complexity of equipment but also because of the rigor and reproducibility criteria now maintained by most researchers. Medical research is a prime example of how the cost of research has gone up with the standard and quality of research in the last few decades.
So, while we reap the rewards from science, we need to also understand ‘who pays for science’? There are three main avenues researchers seek funding from, depending on the arena of science – government agencies, trust funds and private pharmaceutical companies. While invaluable funding from these groups makes today’s technological innovations and advancement in knowledge possible, it might also introduce biases. For example, a clinical trial sponsored by a pharmaceutical company paying for a new seizure medication might influence the trial's design in ways that subtly favor their drug and even the geographies that they would like to market the drug in. Besides, in the last few decades, the US alone has generated more than half of the world’s medical research funding. This begs a serious question - does the funded research then mainly focus on diseases affecting masses in rich, high income countries where less than 20% of the entire world’s population resides?
While you ponder over the above-mentioned question, I would like to draw your attention to an interesting interactive tool by the Institute for Health Metrics and Evaluation in Seattle. This tool shows the world’s health levels and trends using estimates from the Global Burden of Disease (GBD) study.
Charts comparing DALYs, i.e. disability-adjusted life years (sum of years of life lost to early death and years lived with disability), in high SDI* (top chart) and low SDI* (bottom chart) geographies. Source: GBD Compare *SDI is a composite average of the rankings of the incomes per capita, average educational attainment, and fertility rates of all areas in the GBD study that identifies where countries sit on the spectrum of development.
In high SDI* (socio-demographic index) countries (top chart) mostly noncommunicable diseases prevail including heart and lung diseases, back pain, drug use disorders, depressive disorders (blue) — diseases that are typically associated with lifestyle choices such as diet and exercise. In low SDI* countries (bottom chart), while the prevalence of such lifestyle-associated diseases is increasing, communicable diseases such as diarrhoea, tuberculosis, and malaria (orange) that have plagued these countries for a long time also continue to prevail. This difference is possibly a two-part problem: (1) either there is not enough availability of medicines which could be because of lack of funds (~60% of all health research and development funding comes from the for-profit private sector, making it likely that research that is profitable will be preferred) or lack of adequate research capabilities like competent scientists, ethics, etc.; (2) or there is not enough accessibility of medicines and basic health determinants like clean water, adequate nutrition, etc. The latter is obviously worse because it means that vulnerable people are suffering and dying of preventable and treatable diseases. However, there is also a long-standing idea of ‘10/90 Gap’ that refers to the mismatch between disease burden and the financial resources devoted to health research. In other words, only 10% of health research funding is devoted to the study and relief for diseases that burden 90% of the world’s population. Unfortunately, but not surprisingly, the groups most affected due to such unequal distribution of research dollars are the underprivileged people, especially those living in low- and middle-income countries.
II. Rare Diseases and Neglected Tropical Diseases
Diseases that affect very few people in the developed countries (rare diseases) or that affect people in poor countries (called neglected tropical diseases (NTDs)) are often misdiagnosed and suffer from a lack of enough treatment options. Neglected tropical diseases (NTDs) cause anaemia, blindness, stunt growth in children, lead to cognitive impairments, complicate pregnancies, and result in thousands of deaths each year. People living in extreme poverty often suffer from more than one NTDs at the same time, which also affects their ability to make a living and move out of poverty.
Roughly 7,000 rare diseases affect over 350 million people around the world, most of which are without an approved treatment or therapy. In addition, more than 1 billion people in developing countries suffer from NTDs that are caused by bacterial and parasitic infections. Both these types of diseases suffer from little research funding, fewer specialists, limited data about the condition, and lack of awareness among the general public as well as healthcare professionals. Given the scale and impact of these diseases on public health, further research into these conditions is needed to provide the required data and adequate treatment options for achieving the Sustainable Development Goals and universal health coverage.
Number of people requiring interventions against NTDs, 2015
III. Progress towards eradicating NTDs and Rare Diseases
However, it’s not all that bad!
Implementation of five interventions recommended by WHO has led to control of spread of these diseases via sustained expansion of disease control programmes in countries where NTDs are most prevalent. These five interventions are as follows:
Preventive chemotherapy (PC) is a disease control strategy in which periodic mass drug administration is carried out in communities or provided to specific target groups, such as school children. This is aimed at reducing morbidity as well as transmission of the disease. As shown in the figure below, PC coverage has increased tremendously in the last 10 years. WHO offers a ‘progress dashboard’ showing the remarkable impact of PC individually on some NTDs including lymphatic filariasis, trachoma, onchocerciasis, etc.
Source: WHO’s ‘progress dashboard’ 2011-2020
Innovative and intensified disease management employs various interventions to relieve the symptoms of diseases where the existing tools are limited. As shown in the figure below, these interventions have proven effective in reducing the number of new cases for several such diseases. WHO’s ‘progress dashboard’ shows the achievements of programs working within the framework of innovative and intensified disease management individually on some NTDs including Rabies, Dracunculiasis (GW), Yaws, Chagas disease, leprosy, human African trypanosomiasis (HAT), and visceral leishmaniasis (VT).
Source: WHO’s ‘progress dashboard’ 2011-2020
Vector ecology and management includes guidelines and approaches for vector control to prevent and control the transmission of vector-borne diseases.
Veterinary public health services are aimed to tackle the neglected zoonotic diseases that are naturally transmitted from vertebrate animals to humans and vice versa, such as rabies.
Provision of safe water, sanitation, and hygiene (WASH) is critical for preventing and providing care for most NTDs
Besides recommendations by WHO, there have also been incentives from regulatory bodies including USFDA and EMA to incentivise pharmaceutical companies to invest in research for diseases that may not be financially lucrative. For instance, in Oct 2016 USFDA finalised a guideline to provide information on the award of Priority Review Vouchers (PRVs) to sponsors of approved tropical disease (list can be found on the USFDA website) drug applications. Under ‘Article 58’ EMA cooperates with WHO to provide scientific opinions on high priority human medicines that are intended exclusively for ex-EU markets. The aim of this collaboration is to facilitate patient access to essential medicines in low- and middle-income countries, including new or improved therapies for unmet medical needs. As part of this program, fexinidazole, developed by Sanofi in collaboration with DnDi, received approval for distribution in endemic countries in 2019 for the treatment of sleeping sickness.
Similarly, rare diseases have also been getting increased attention over the years. Congress passed the Orphan Drug Act in 1983 to incentivize the development of drugs to treat rare diseases, and USFDA has since approved hundreds of drugs for rare diseases. As a part of the act, the sponsor gets potential 7 years of market exclusivity after approval of the drug, Orphan Product Grants Program provides funding for developing products for rare diseases, USFDA awards Rare Pediatric Disease Priority Review Vouchers, etc. A similar program was launched in the EU in 2000.
Cumulative count of Orphan Drug Designation by region, per year
IV. Future challenges and opportunities
Significant efforts have been made to bridge ‘the 10/90 gap’ and achieve universal health coverage. However, we still have a long way to go! With rare diseases, the effects of FDA and EMA programs are not uniform and some diseases are still prioritized over others for new drug development as well as 95% of rare diseases still do not have treatments. With NTDs, mass drug administration continues to be the key area that needs support and commitment such that areas at risk are not only efficiently monitored but also encouraged to develop robust and dependable health-delivery systems to ensure long-term progress in human development. This includes a data repository to allow informed decision-making, training medical personnel in underdeveloped countries, etc. In the pursuit, leveraging policy windows and greater involvement of governments and civil society of endemic countries can also help drive actions to address NTDs in the pathway to sustainable development. In addition, more initiatives are needed to encourage new research initiatives on rare diseases and NTDs. Lastly, while it remains to be seen how above-mentioned activities will adapt to the newly changed COVID-19 environment, there is an even greater need for such interventions and mitigation activities to be in place.
I would like to thank Rohil Jain and Mainak Mustafi for their thoughtful feedback and suggestions for improving the article. In addition, I deeply thank Charu Mehta for not only providing this opportunity but also helping with the overall conceptualisation of the article.