Volunteering for clinical research trials can be a rewarding experience, not least financially – or so the research companies would have us believe. To offer oneself as a guinea pig for the future benefit of others is undoubtedly a selfless act, but under what safeguards are these studies conducted? With the clinical drugs trial disaster in Rennes, France, in January 2016 – where one volunteer died and three others were left with irreversible brain damage – clinical research studies are once again under the microscope…
“You don’t want to do that – you might grow a second head.” Thus opined my friend when I told him I’d signed up to test a new hygiene product for some extra cash. Quite how a mouthwash might result in an extra noggin is anyone’s guess, but with several high-profile accusations of clinical malpractice levelled at pharmaceutical and drugs testing companies in recent years, I decided to conduct a little research of my own.
With the announcement in September 2014 that an NHS communications manager, Ruth Atkins, had volunteered to be injected with an Ebola vaccine containing genetic material from the Zaire strain of the virus, the media were champing at the bit with speculation and doom mongering. Few seemed interested in reporting that the vaccine is based on a benign cold-like virus found in chimpanzees, that it cannot cause the volunteer to develop Ebola, or that it simply allows the recipient’s cells to release a protein and thus create an immune response. That wouldn’t make good copy.
Such fears, of course, are not without precedence. From the horrors of Nazi doctors conducting experiments on concentration camp victims during World War II, to the Thalidomide scandal of the late 1950s, clinical research communities have faced serious PR problems when it comes to allaying our concerns about the work they do in the name of progress. But that plays into the hands of the detractors somewhat, since many thousands of clinical research studies are conducted every year, without incident, without side effects and without hitting the headlines. And whereas all drugs testing comes under the banner of clinical research, not all clinical research studies concern drugs testing.
A clinical trial is defined as either a biological or behavioural research study on human test subjects, designed to answer specific questions regarding anything from the effects of a new vaccine or drug, to effective treatment models for biological or behavioural disorders, to the requirements of certain health conditions, or for testing new devices and healthcare products intended for the open market. For the majority of those who volunteer for such studies, the experience has only ever been positive.
Former social care support worker Neal, 56, started volunteering with Intertek – a testing and certification company for the chemicals and textile industries – after a friend, already a volunteer, recommended it.
“I was waiting to start a new job and needed some extra cash. As a single parent, my reasons for signing up were mostly financial, but I was also curious about the work they were doing. I ended up testing a new deodorant.”
So how did he find the experience?
“It was fascinating. I met some nice people, and the money came in handy,” recalls Neal. “The deodorant gave me a rash, but it soon cleared up.”
Would he ever consider drugs testing?
“I wouldn’t rule it out. It would depend what it was for. I’m quite open to new experiences. Last year, I took part in a sun burn study for Manchester University that involved taking several biopsies from my buttocks.”
Testing a new deodorant is classified as a ‘low-risk’ study, but under UK statutory law is every bit as subject to the stringent regulations laid down in the guidelines for Good Clinical Practice (GCP) as would be, say, a new anti-viral drug or painkiller. GCP, considered to be the clinical trials ‘bible’, is an international quality assurance on how clinical trials should be conducted, and is designed to protect the rights and health of volunteers.
Clinical trials on humans constitute only a small part of the extensive research that goes into developing a potential new treatment, drug or product. With the occasional exception, where it is deemed expedient to fast-track a study (Ebola vaccine being a case in point), any proposed trial must undergo several years of rigorous laboratory research before it is approved by regulatory bodies and reaches Phase 1, the stage where human test subjects are involved.
Subjects Sharon and Danny, a married couple in their 40s, first started volunteering four years ago after a recruitment leaflet dropped through the letterbox. A private tutor and a sound engineer respectively, they have taken part in numerous skin, hair and dental studies.
“We’re both self-employed, so can fit the studies around our work,” says Danny. “The process is easy and the studies are always interesting.”
Sharon agrees: “I like doing a variety of things to make money, and as a science teacher I’m always fascinated by front-line research.”
Despite some initial reservations from friends and family, the couple are happy to recommend this type of clinical research to anyone in reasonably good health. “I think some people mistake product testing for drug trials,” says Danny, “which we wouldn’t consider.”
It is, perhaps, unsurprising that even seasoned volunteers shy away from drugs trials when you consider what happened in 2006 at Northwick Park Hospital, London. Six male volunteers were contracted by the US drugs testing company Parexel to test a new anti-cancer drug known as TGN1412.
Within minutes of being injected, the men began vomiting, their heads puffed up to twice their size and some began slipping in and out of comas as they showed signs of multiple organ failure. Thankfully, all the volunteers recovered, although one was reported to have had his toes amputated, but the incident raised serious concerns about trial procedures and medical ethics in general.
An interim report by the Medicines and Healthcare Products Regulatory Agency found that Parexel had conducted the study according to protocol and concluded that “the serious adverse reactions experienced by the volunteers were the result of an unpredicted biological action.” The episode was played down by the industry, but it is fair to say that drugs testing companies and clinical trials in general took a critical drubbing.
In his Sunday Times bestseller Bad Pharma: How medicine is broken and how we can fix it, Doctor Ben Goldacre sees the events at Northwick Park as symptomatic of a wider, systemic problem with research studies, where interested parties such as pharmaceutical companies can exert, quite legally, undue influence on the results of clinical research.
“Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques which are flawed by design, in such a way that they exaggerate the benefits of treatments. Unsurprisingly, these trials tend to produce results that favour the manufacturer. When trials throw up results that companies don’t like, they are perfectly entitled to hide them from doctors and patients, so we only ever see a distorted picture of any drug’s true effects.”
A writer for the Guardian and advocate of the AllTrials campaign for full disclosure of all clinical trial results, Goldacre contends that the incidents at Northwick Park and at the Pontchaillou Medical Centre in Rennes, France, could have been avoided if all researchers were compelled by international law to publish and share their data.
“We need to ensure that all trials report their results within a year at the latest; we need to measure compliance with that; we need stiff penalties for companies who transgress; and we need doctors and academics that collaborate in withholding trial data to be held personally responsible, and struck off.”
Bad Pharma is a complex and difficult book, its depth and scope too far-reaching to go into much detail here, but anyone thinking of volunteering for clinical drugs trials would be well advised to read this seminal work first.
Not everyone has a horror story to tell when it comes to drugs testing. Maggie was a barmaid in her early 20s when she took part in residential drugs trials with Medeval, later known as Icon Development Solutions.
“I had friends who’d done it before,” she says. “All said it was easy money, nothing to it, perfectly safe, etc. I had been broken into twice and was just desperate to move. I just wanted to make some money to put a deposit down on a flat.”
Was she concerned about possible side-effects?
“No. I did two trials, both for drugs already in use, which I considered to be less scary. One involved being woken up every morning with a shot of vodka. So what’s not to like?”
So she’d do it again?
“I couldn’t even if I wanted. I have a history of depression, which would automatically exclude me from most studies. That and the fact my mum, who was a nurse at the time, was horrified when she heard what I was doing. Looking back, I think she was maybe right to be concerned. She was much more aware than I was that things can go wrong.”
As they did in India between 2008 and 2011, when over two thousand deaths were recorded during clinical drug trials in the country, forcing the Indian government to tighten the regulations surrounding what was described as “a culture of impunity for drug research companies and the doctors who work for them.” The researchers involved, many of them multinational pharmaceutical companies, were initially drawn to India (where the clinical trials industry is estimated to be worth £326 million) for several reasons, including patient availability, low costs and a “friendly drug-control system.”
The companies concerned defended themselves by insisting they were conducting trials on patients who had little or no hope of cure; that in consequence they could not be blamed for their deaths; and that the standards applicable to all clinical trials in India are no different from those in the United States and the European Union. With the resultant change in the law, however, many of these companies, led by America’s top research centre, the National Institute of Health, subsequently pulled out from India – a move which did little to assuage the concerns of the World Health Organisation and the general public.
Little wonder, then, at the media interest surrounding the fast-tracked Ebola trial at Oxford University and Ruth Atkins’ decision to be the first test subject for the new vaccine. Atkins, a former nurse in the NHS, was reported as saying: “I volunteered because the situation in Africa is so tragic and I thought being part of this vaccination was something small I could do to hopefully make a huge impact.” She went on to add that she felt fine after her injection and that the vaccine “felt no different to being vaccinated before going on holiday.”
In 2014 the Ebola virus killed more than 2,400 people in Africa, the world’s largest outbreak since the disease was first discovered in 1976. According to the World Health Organisation, the strain has a mortality rate of up to 90 percent, and it is for this reason that the new study, which will involve up to 60 volunteers, has been backed by the Medical Research Council and the UK Department for International Development. Funding for the trial comes in part from a £2.8 million grant from the Wellcome Trust.
Leading the study, Professor Adrian Hill of the Jenner Institute stressed that all the volunteers were safe, stating: “We are not doing the trial itself any faster. It’s the arrangements, the approval for the trial from manufacturers, regulatory bodies and the ethical council that has happened in record time, when under any other circumstances it would have taken years. The tragic events in Africa demand an urgent response.”
It remains to be seen if the Ebola vaccine proves an effective treatment, but no one in their right mind would deny the need for clinical research trials; they are essential for the development of new medicines and modes of treatment. And how else will we find the cure for cancer?
However, the regulations and codes of conduct under which studies are carried out need to be of a universally accepted standard set in international law, and not be dictated by the financial considerations of multinational pharmaceutical companies, private health bodies or cash-strapped governments.
As for volunteering, it remains with the individual to decide what they are willing to participate in and to fully verse themselves on the potential.“I’m not sure I’d recommend drugs testing,” says Maggie, the former barmaid, “it would depend what it was for. I’d say use your common sense. If they want to make you taller or fill you full of hormones, just say ‘no’”.
Studies at a Glance: A Brief History of Clinical Research
The First Clinical Trial (1747)
The first proper clinical research trial came in the wake of the disease scurvy and its catastrophic effects on the welfare of sailors on long distance voyages. Physician James Lind conducted the trial on infected sailors and established beyond doubt that scurvy is caused by vitamin C deficiency, arguably saving many thousands of lives in the process.
The Nuremburg Code (1947)
At the end of the Second World War, numerous Nazi doctors, who had performed human experiments, were tried at the war crimes tribunal in Nuremburg. During the trials, the Nuremburg Code was drafted as a set of standards for judging physicians and scientists who conducted biomedical experiments on concentration camp prisoners. This became the foundation of many later codes intended to assure that clinical research involving human subjects would be carried out in an ethical manner.
The Thalidomide Scandal (1957 – 1961)
In the 1950s, Thalidomide was developed as an anti-convulsant drug and introduced on the German market without any governmental review. Thalidomide was used by expectant mothers to control the symptoms of morning sickness, and lead to many babies being born with severe physical disabilities. The reported number of those harmed varies, but studies indicate that more than 10,000 people worldwide were affected.
The Declaration of Helsinki (1964)
The ethical principles set out in the Nuremburg Code were further elaborated on and clarified by the World Medical Association. The Declaration of Helsinki provided the ethical foundation for the European Clinical Trials Directive as well as all national clinical research legislation.
Good Clinical Practice (1996)
The clinical trials ‘Bible’ was introduced, the contents of which were implemented into the European clinical trial quality standards through the Clinical Trials Directive (2001) and the GCP Directive (2005). These directives have been turned into law by each of the member states of the European Community.
Bad Clinical Practice (2001)
Published simultaneously in twelve major journals, a joint editorial exposed the levels of control sponsors exert over clinical trials and attacked the use of contracts that allow sponsors to review the studies prior to publication and, if they wish it, to suppress the results.
Ugly Clinical Practice (2012)
Pharmaceutical giant GlaxoSmithKline was fined $3 billion for civil and criminal fraud after pleading guilty to charges relating to unlawful promotion of prescription drugs, bribing doctors, withholding data and making false and misleading claims about the safety of drugs.
AllTrials Campaign (2013)
Calling for all trials to be registered, with the results reported and made publicly available, the AllTrials campaign launched in January. Within months the campaign grews to become the mainstream, normative position in the UK, with the Medical Research Council, the Wellcome Trust and even GlaxoSmithKline signing up to a new agreement for transparency in research.
Trial and Trial Again (2015)
Former priest Adrian Hailer announced to the UK press he was to sue the drugs company Novartis after he developed brain damage following a drugs trial for a medication to treat a bone marrow condition. Novartis stated they intended to contest the claim as they had been “unable to establish a causal relationship between the trial and Mr Hailer’s condition.” The drug was approved by the European Union in August 2012.