According to the largest clinical trial registry in the world, out of 3,500 COVID-19 clinical trials, only five are ongoing in Nigeria.
‘All things are poison, and nothing is without poison; the dosage alone makes it so a thing is not a poison’. — Paracelsus
It is very common for the average individual to walk into a local pharmacy, pick up any medication, and trust that it will provide relief from the ailment it is needed for. Many non-pharmaceutical professionals, especially in Africa, care less about the process that brings the drug to market and more about the outcome—which is the relief. At the onset of the COVID-19 pandemic, many rallied against the idea that Black people could be subject to manipulative drug testing, but much of the media attention paid to this was based on half-truths. Africans have long been on the losing end of the US$44 billion pharmaceutical testing industry, but not in the way that the story is often told.
DEVELOPING DRUGS: THE PHASE PROCESS
The drug development process begins when a savvy scientist or individual discovers a chemical or herb that they believe can cure a disease. After making chemical or herbal mixtures in the lab, and testing on animals, the chemical or herb becomes a potential drug and is taken through different phases of testing in humans, known as clinical trials. In phase I, the drug is given to healthy volunteers to make sure that it does not make healthy people sick. During this phase, scientists monitor what the drug does to the body and calculate the highest dose that a healthy individual can take before any harm or side effects emerge. In this phase, individuals who volunteer to go through this process are often given monetary compensation for their willingness to risk the unknown impacts of new drugs.
It’s not just okay for a potential drug to be safe for human consumption, there must be proof that it can cure the intended disease. At the end of successful phase I trials, the potential drug is taken to phase II. During phase II trials, a small group (typically less than 100 people) of individuals who have the disease intended to be targeted are recruited to take the drug. This is done with the intention of disease treatment. If the potential drug shows promise during phase II, it is taken to phase III, where it is tested on a larger number of sick people for a longer period. If the potential drug proves to be successful, it receives approval from a drug regulatory agency like Nigeria’s National Agency for Food and Drug Administration and Control (NAFDAC) to be sold to consumers, in pharmacies and hospitals. After approval, a fourth phase commences, to ensure that the potential drug does not cause harm while it is used by professionals to treat diseases.
While this process seems straightforward, it can be influenced by major external factors, such as something I like to refer to as the ‘access effect’. Typically, the simple phase process can easily cost as much as US$1 billion. As this is a costly process, pharmaceutical companies prefer to develop drugs for populations that can pay—they are, after all, in it for the profit. The idea of profit-making shifts the business case away from low- and middle-income countries, meaning that drugs are typically not developed according to the need of these countries. Clinical trials, therefore, become very strategic, as companies like to test their drugs in countries where they can gain quick regulatory approvals, register patents and sell to make profit. This process makes drugs expensive for low- and middle-income countries, thus cutting off access to life-improving medication.
In addition to the low-income levels of West Africa, the absence of clinical trial infrastructure acts like a double-edged sword limiting drug access to the region. A quick search through clinicaltrials.gov, the largest clinical trial registry in the world, reveals that of 3,500 COVID-19 clinical trials, only five are ongoing in Nigeria. None are sponsored by companies in the pharmaceutical industry but are mostly academic clinical trials.
THE PROBLEM WITH PATENTS
Patents that allow companies to hold 20-year marketing monopolies on their development do not in any way help to reduce drug prices. In the race to develop a COVID-19 vaccine, Gilead Sciences, which made initial headway with its promising antiviral drug remdesivir, priced the drug to cost between US$2000- 3000 for a five-day regimen. However, newly emerging COVID-19 vaccines are much cheaper than Gilead’s remdesivir.
High drug prices and the marketing monopolies provided by patents also extend to developing countries. Sickle cell disease is the most common genetic disease on earth, and the majority of individuals with the disease live in Nigeria. Oxybryta, a drug developed to treat sickle cell by Global Blood Therapeutics (GBT) did not enrol patients from Nigeria during its testing phases. It was approved by NAFDAC’s American equivalent, the Food and Drug Administration (FDA) in 2019 and is priced at US$10,000 per month and US$125,000 per annum. It is an expensive drug even by US standards—a clear indication that it was not developed with West African patients as the target consideration. If clinical tests had been carried out in Nigeria, at least some sickle cell patients may have had the opportunity to benefit from a reduced disease burden, even if they were unable to purchase the drug after approval.
In addition to reduced access to medication, there are also economic costs to not participating in industry trials. Pharmaceutical firms recruit companies known as contract research organizations (CROs) to help with the process of conducting clinical trials. These firms handle everything from patient recruitment to data collection and analysis, drug shipment, and even trial monitoring at selected hospitals and clinics. For one potential drug, a pharmaceutical organization can work with as many as five CROs just to get the job done. This has a knock-on effect on job creation even at the micro-level. From data entry staff who need no qualifications to mid-level study monitors, supply chain associates, and regulatory experts as well as highly qualified pharmacists, biostatisticians, and medical doctors that play important roles throughout the process. The near absence of this industry in West Africa means the region misses out on economic and job opportunities.
Some may think of the health industry as one that should not be quantified or viewed through a monetary lens, so let’s talk about healthcare effects. Nigeria has formal and informal pharmaceutical industries. The formal sector is heavily focused on drug importation, with the manufacturing sector more focused on the production of generic drugs, which are drugs that have lapsed patents. The informal sector focuses majorly on local herbs and concoctions mixed to cure a myriad of diseases and ailments. The absence of drug trials to help prove that these mixtures are effective, and lacking dosage calculations to help prevent overdosing, leaves consumers at risk of developing underlying health complications such as chronic liver or kidney damage. The absence of clinical trials and relevant clinical trial infrastructure have been detrimental to local drug development efforts, as herbal remedies remain untested and scientific discoveries remain in laboratories across the country.
Rather than focus on the flaws within the African drug development system, it is worth assessing the opportunities that abound within the industry. Black people are recruited to represent Africans within the many drug trials that take place in South Africa and the US, but they remain under-represented. Black people are also short-changed during drug development because the potential negative effects that some drugs may have on the broader African population are not taken into consideration. This is worth noting, even though it may not be a significant scientific issue for concern. The opportunity for diversity within the global clinical research industry remains untapped, especially for western Africa, and is a window of opportunity for driving job creation, increasing innovation in the region, and improving the medical sector; even as the industry is known for its tendency to encourage remote working, a norm it developed before the COVID-19 pandemic.
Undoubtedly there are issues with drug development that are causes for concern. Are there safety and ethical issues with clinical trials? Yes, there are. Drugs cannot be effectively tested in countries with weak institutions because gross violations of ethics can take place. Frequently cited examples include the 1932-72 Tuskegee syphilis trials where there was ethical foul play on African Americans and the 1996 Pfizer trials that took place in Nigeria. During the 1996 trials, Pfizer was accused of gross ethical violations while testing Trovan, an antibiotic, on children with meningitis in Kano state. There were allegations of bribery, forgery and improper consent from parents of the children. Eleven children died during trials and others were left with complications after taking the drug. Although Pfizer did not acknowledge any wrongdoing, it reached an out of court settlement with the victims in 2009.
Companies have been found to cut corners when not adequately monitored, and this is not peculiar to Africa. Between 1994 and 1998, GlaxoSmithKline (formerly SmithKline Beecham) carried out Study 329 in the US. This was a trial of the anti-depressant Paroxetine, and was conducted among teenagers. The company made inappropriate claims about the safety and effectiveness of the drug in a research article, and marketed the drug using misleading data. It was later discovered that rather than work as an effective anti-depressant, Paroxetine increased suicidal thoughts and behaviours among patients. Although, the company was fined US$3 billion by the US Department of Justice for withholding data, Study 329 changed the way clinical trials were conducted. Wariness of potential ethical concerns should not mean that African nations disregard the immense value of this industry, instead, they should consider these ethical challenges as opportunities to strengthen institutions, using lessons learned from such situations.
CLINICAL TRIALS: SOME POSITIVE IMPACTS
These few examples of poor ethics do not negate the positive impact of the numerous clinical trials currently taking place globally, as foundations such as the Global Alliance for Vaccines and Immunizations (GAVI) and the Access to Medicine Foundation put pressure on large pharmaceutical companies to do better. In 2019, NAFDAC laid down regulations for the conduct of clinical trials in Nigeria. A similar strategic push from NAFDAC could encourage the involvement of local and foreign private sectors to establish and expand the industry and tap into a global industry that can solve economic challenges in the region.
One unique way to start is by expanding current regulations to include managed or expanded access, where patients in dire need of promising medication can be included in ongoing global trials. Clinical trials have helped to strengthen healthcare institutions around the world, and those who participate in clinical trials either as healthy volunteers, patients, low-level workers, or experts make a significant contribution to science and to a better and healthier world⎈
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