In 2003, Chinese villager Zhen Suxia was desperately looking for a cure for AIDS after being infected with the virus by blood traders. Seeing fellow villagers dying around him, he signed up to a medical trial at Ditan hospital in Beijing. The three-month experiment was for a drug called VGV-1, developed by Californian biotechnology company Viral Genetics. The US company was looking to experiment with its newest drug in a low-cost environment, and as an HIV epidemic ravaged the county, an army of willing participants such as Zhen funnelled through the hospital doors, lured by the promise of life-changing treatment. Unfortunately, soon after receiving their initial dose the participants started reporting rashes and high fevers. Shortly after leaving the hospital, two passed away.
Sometime later it was revealed that the trial had been conducted without the approval of China’s Food and Drug Administration, and the potential health risks had been deliberately obscured.
25.2%
Global clinical trials that emerging market countries are expected to account for by 2020.
WHO
The Ditan hospital experiment is undoubtedly an extreme example of the pitfalls of conducting a clinical trial in a less familiar market. Despite such incidences, emerging nations still represent viable research opportunities for pharmaceutical and life sciences companies, particularly as the patent cliff continues to eat into pharmaceutical industry profits in mature economies.
Brazil, Russia, India, China and South Africa all have swelling middle-class populations, enabling more citizens to afford essential care or purchase private health insurance. Simultaneously, governments are striving to establish universal healthcare systems, such as JKN in Indonesia and Seguro Popular in Mexico.
Zouhair Attieh, AUST
Moreover, the price of performing trials in emerging nations is significantly cheaper than in more developed counterparts, and patients are more willing to participate in medical trials.
It’s no surprise then that, by 2020, emerging markets are expected to account for 25.2% of global clinical trials, a 15.7% increase from current levels.
As Rachel Howard, regulatory affairs coordinator at Novartis Pharmaceuticals, has suggested, “Greater purchasing power and improved market access are growing the opportunity for innovative medicines in these markets. The vast populations of many emerging markets mean they constitute a high proportion of the world’s next billion patients, which pharma simply cannot afford to overlook.”
A chronic problem
Shifting demographics and lifestyle changes in developing nations are opening up valuable research opportunities for pharmaceutical companies.
WHO estimates that 80% of diabetes deaths occur in low and middle-income countries, predicting that such deaths will double between 2016–30. According to the International Diabetes Federation, India currently represents 49% of the world’s diabetes burden, with an estimated 72 million cases in 2017, a figure expected to almost double to 134 million by 2025.
25%
The predicted increase in cases of diabetes and cancer in India over the next 10 years.
WHO
Overall, chronic diseases are predicted to grow by 20% or more by 2030, meaning emerging market countries will require long-term access to medication for these conditions. Conversely, rapid urbanisation has fuelled a rise in the spread of infectious diseases in emerging market cities. India has seen the rapid spread of dengue and chikungunya, with hospitals in Delhi most affected. According to studies by the CNRS, the Pasteur Institute and the National Institute of Malaria Research, nearly 40% of the population of New Delhi have been infected by the dengue virus at least once in their lifetime.
This dual threat of chronic and infectious diseases provides opportunities for pharmaceutical companies to invest in research and development programmes. It might also be time to give neglected tropical diseases (NTDs) some attention, as limited return on investment and a lack of localised public funding has seen little or no research in this area. During 2000–11, only 1% of new chemical entities approved were for NTDs.
As the era of blockbuster drug treatment fades and consumers in mature markets put manufacturers under increased pricing pressure, alternative avenues will need to be explored. A recent report by Access to Medicine, on the research and development strategies of the world’s 20 largest drug companies, shows that multinationals are increasing efforts to combat neglected tropical diseases, such as sleeping sickness and river blindness.
In 2010, nine of the companies evaluated were working on at least one research and development project looking into NTDs, that figure has since risen to 15. The research and development pipeline for NTDs has also more than doubled since 2014.
Trials and tribulations
That being said, conducting trials in emerging markets can expose researchers to a raft of difficult scenarios, many of which are born out of the unique and challenging regulatory pathways in these countries.
In their 2017 paper on the influence of emerging markets on the pharmaceutical industry, Maya Tannoury and Professor Zouhair Attieh have observed that many of these markets “are facing considerable challenges, including underdeveloped healthcare infrastructure, cost-containment policies, time constraints, a shortage of expertise, economic crises and corruption”.
The lack of infrastructure and slow, inefficient bureaucratic processes of emerging markets have been well documented, making many difficult places to conduct research programmes.
However, with its vast urban population and position as the world’s second-largest pharmaceutical market, China is poised to become a world leader in clinical trials.
But problems with protecting participants and poor transparency make it an unreliable country in which to conduct clinical research. A survey by the country’s chief food and drug regulator in 2016 revealed the shocking extent of the countries loosely regulated clinical trials industry, concluding that 80% of data in the country was ‘fabricated’. Unsurprisingly, fewer than 5% of trials registered on the site clinicaltrials.gov have been conducted in the country.
India presents a similar challenge, albeit with a population that is predominantly rural. According to the World Bank, 67% of the Indian population live in rural areas, and many have to travel long distances to gain access to basic healthcare facilities, which often fall significantly below western standards.
Despite efforts by the Central Drugs Standard Control Organization (CDSCO), a recent analysis by WHO highlighted the numerous regulatory and ethical concerns regarding the conduct of clinical trials in India. As a result, the number of active clinical trial sites in the country has decreased over the past five years.
The right people for the job
The need for experienced and highly trained staff in clinical trial settings also presents a significant challenge. Skills and expertise are scare in such countries, and the need for qualified staff often places undue pressure on companies to find trained expatriates, a tough task given that a majority of candidates move elsewhere. A survey by Strategy& concludes that employee turnover rates in developing markets are in double digits due to the loss of talent to competitors. Success in such regions rests heavily on local representatives having an intimate knowledge of culture, language and regulations.
Moreover, despite the prevalence of chronic diseases, such as diabetes, in emerging markets, it is still commonplace for pharmaceutical companies to test drugs in these markets for western citizens.
This raises practical implications, given that the lifestyle, diet and body type of the participants is often markedly different to citizens in more developed nations.
For instance, western diabetes sufferers tend to be heavier than those in emerging nations, a factor that could have a significant bearing on how certain drugs work. Drugs demonstrated to be effective in treatment of naive populations may also be less effective among patients already receiving multiple effective therapies.
Alongside these practical issues sit the ethical implications of giving access to patients who cannot afford, or do not have access to, effective treatment outside of the trial. If a patient is responding well to a therapy, is it ethical to withdraw treatment at the end of the study if there is no alternative treatment available in their country?
There are no easy answers to such questions, but it is encouraging that certain countries, such as Brazil, allow principal investigators to request continuation of treatment from sponsors.
1/4 Of pharmaceutical industries conducting trials in emerging markets attributed past failures to a lack of patience and long-term planning.
Strategy&
Keep moving forward
Given the potential pitfalls of conducting trials in less developed nations, it is vital that pharma companies analyse the infrastructure, facilities and staff when selecting certain countries for trials.
Roche Diagnostics cites these three areas as pivotal factors in selection, advising that such countries demonstrate “experience in clinical trial management activities, which include independent ethics committees and a strong regulatory framework”.
Likewise, the company recommends that staff selection is “based on scientific expertise, training and qualifications, as well as site-specific competency and feasibility”.
Rachel Howard, Novartis Pharmaceuticals
While it sounds obvious, long-term strategies tailored to match the emerging market of choice are a crucial place to start.
In another survey by Strategy&, 25% of pharmaceutical industries conducting trials in emerging markets attributed past failures to a lack of patience and long-term planning. The same report cites a high-profile pharmaceutical executive who says, “Our biggest mistake was to treat emerging markets like mature markets.”
As Howard has said, “Multinational companies cannot afford for conducting local clinical trials or understanding local preferences to be an afterthought in their drug development plans. No longer can they get away with just rolling out whatever tested well in mature markets.”
As pharmaceutical and life sciences companies look to emergent nations full of new research and development opportunities, it is vital that they choose their destinations wisely, and adapt to suit the culture and infrastructure of such countries. If they succeed, they could gain access to the world’s next billion patients.
