International pharmaceutical companies experiment with the health and even the lives of South African patients, with clinical tests often conducted in a unethical manner on patients in that country. This is the conclusion of a report on clinical tests by Wemos – a Netherlands-based non-profit organization that advocates the right to health of people worldwide – entitled “The Clinical Trials Industry in South Africa: Ethics, Rules and Realities.”
The report focuses on South Africa because of the popularity of the country as the clinical trial destination of choice for the multinational pharmaceutical industry. Widespread poverty and lack of access to adequate and affordable health care means it’s easy for companies to recruit trial subjects: for the most vulnerable, taking part in clinical trials is often seen as a way to get treatment that’s otherwise out of reach.
Drug companies are quick to exploit this opportunity. According to the report, the clinical trial business in South Africa is valued at around €250 million ($329 million).
On the whole, however, very little information other than business and profit analyses is available on the topic of clinical trials. There is a lack of media coverage and a dearth of NGOs and activists focusing on the monitoring of clinical trials or patient rights. Yet given the increasing presence of drug companies and contract research organizations – to whom the tests are often subcontracted – in countries with high rates of poverty and illiteracy, the potential for ethical and human rights violations is high.
Suffering test subjects given a placebo when treatment is available
Following several months of research done in cities like Johannesburg and Durban — notably on conditions such as asthma, schizophrenia and rheumatoid arthritis — the report by Wemos identifies three main ethical issues: the use of unethical placebo tests, the lack of care given to patients after the trials, and the fact that many of these tests’ main aim is simply to preserve the companies’ market share.
The major problem identified is linked to placebo-controlled trials. In these situations, the effect of a drug is compared against the effect of a placebo – an inactive substance, often a sugar pill. Subjects do not know whether they are receiving real or placebo treatment. The results obtained in the different groups are then compared. In theory, this is an effective way to determine a treatment’s efficacy. In practice, this means that some patients don’t actually get treatment.
This is why placebo-controlled trials have always been controversial. According to the Declaration of Helsinki, which regulates clinical trials worldwide and was adopted by the World Medical Association in 1964, placebo-controlled trials can be conducted only in circumstances where there is no proven treatment available. Additionally, it stipulates that “extreme care must be taken to avoid abuse of this option.” Although not binding, the document serves as a reference for organizations and governments alike.
The United States and European countries have enshrined the provisions of the Declaration of Helsinki in their own regulations. As a result, these countries’ medical authorities are less likely to approve placebo trials due to ethical concerns.
In 2008, however, in a very controversial decision, the U.S. Food and Drug Administration (FDA) ruled that drug companies no longer needed to comply with these international guidelines in clinical trials conducted outside the United States. This made it easier for companies and their subcontractors to conduct unethical clinical trials in countries with poor regulatory systems.
Meanwhile, the sad irony is that the FDA still requires placebo-controlled clinical trials. “The FDA prefers placebo-controlled trials because they are ‘neater’, need fewer subjects, [with] easier endpoints,” says Professor Lainie Ross, a pediatrician at the University of Chicago.
In Europe, the problem is very similar: current EU legislation requires that results from unethical clinical trials that have not been conducted in accordance with the Declaration of Helsinki not be accepted for marketing authorization. Yet, according to a report by the Dutch Center for Research on Multinational Corporations, this principle is being violated: European authorities devote little to no attention to the ethical aspects of the clinical trials submitted and they accept unethical trials as well as trials of poor quality.
Forced to relapse
In other words, the United States and Europe often encourage the offshoring of unethical trials to low and middle-income countries by requiring trials that are rejected by the ethics committees in their own countries. This is certainly the case with placebo-controlled studies.
South Africa appears to have one of the highest rates of placebo-controlled trials in the world. For the pharmaceutical companies, they have two advantages: first, it is easier to show efficacy when testing a new drug against a placebo instead of against an existing therapy; second, studies which compare existing and new drugs require more patients and consequently more time and more money.
For example, over the past years, South African patients have participated in numerous psychiatric clinical trials for multinational companies, often with the use of placebos. One of them is a study started in 2010 to evaluate the efficacy of a substance called Paliperidone Palmitate in preventing the relapse of schizoaffective disorder. Initially, all trial subjects receive Paliperidone. But only some of them will be eligible to continue: half continue to receive Paliperidone, whereas the other half get a placebo.
Proving the efficacy of the test drug means that the patients in the placebo group must experience a relapse in their psychiatric conditions more frequently and sooner than the Paliperidone group.
According to the Declaration of Helsinki, this type of trial can never justify the use of placebo because it involves withholding treatment from seriously ill patients who may run the risk of serious or irreversible harm. In addition, proven current interventions are available.
Just another commodity?
As it happens, the pharmaceutical company involved has another drug, Risperone, used to treat the same condition, but whose patents will expire in 2014. This has led experts to suspect that the trials are actually an opportunity to have a new brand-name drug available once the patent on the older one runs out. This seems to be a common practice: by adding minor variations to their blockbuster drugs, companies try to put a ‘new’ product on the market by the time the patent of the old drug has expired, thereby preserving their revenue stream. This serves their financial needs instead of clinical needs.
Additionally, some experts believe there is no need for new drugs in that field; they say the ones that exist are pretty good if used properly. The problem is that regulators such as the FDA don’t judge whether there are enough anti-depressants or anti-psychotics on the market or whether there is a public health need for such a drug; nor do they require new drugs to be significantly better than existing ones. Instead, they treat drugs like they treat any other commodity, i.e. the company just has to jump through the regulatory hoops – which includes having two placebo trials even when these have no scientific value.
The third issue is the post-trial access to treatment. In 2000, the Declaration of Helsinki, in an attempt to address the potential exploitation of patients as trial subjects, introduced the principle of post-trial access to drugs for people who participate in clinical trials.
Yet, according to the Wemos report, post-trial access to medication remains a rare perk in South Africa. Professor Doris Schroeder, Director of the Centre for Professional Ethics at the University of Central Lancashire (UK), concedes that “it seems eminently unfair to discontinue access to drugs to clinical trial participants who are responding well, when it is clear that their national health service will not pick up where the trial left off. It means refusing to help somebody whom one could easily help. And in the worst case, the participant dies. That’s utterly horrendous, when help is so close.”