The Pharmaceutical Journal
Vol 270 No 7248 p643-644
10 May 2003

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How volunteers and patients who take part in clinical trials are rewarded

Clinical trials depend on the good will of volunteers and patients for their success. Harriet Adcock (on the staff of The Journal) looks into their recruitment and care in the course of a trial

Many people might feel uneasy about taking part in a clinical trial, acting as "guinea pigs" for pharmaceutical companies developing new products. But it seems that there is a plentiful supply of willing volunteers in the United Kingdom, many enticed into trials by the financial carrots being dangled before their eyes by clinical trial units.

Nevertheless, efforts are made to ensure that the risks to volunteers and patients participating in trials are kept to a minimum.

Recruitment of volunteers

Dr Dipti Amin, vice-president phase I services and head of Guy's Drug Research Unit in London, says that most healthy volunteers at the GDRU are recruited through word of mouth. "Volunteers recommend the unit to their colleagues and friends, and we get phone calls from the volunteers asking if they can take part in trials," she says.

When word of mouth is not sufficient, other methods are employed, most commonly advertising in the press or on local radio. Increasingly, the internet is used to attract volunteers and advertisements have sprung up on buses and the London Underground.

Dr Amin explains that all advertisements have to be approved by an ethics committee to ensure that they are balanced. It seems that recruitment strategies work well and trial units rarely struggle to attract the requisite number of healthy volunteers. However, success can depend on the type of volunteer needed and the location of the trial. Units try to maximise recruitment by using an appropriate advertising forum for the target volunteers.

If young volunteers are being sought, advertisements are more likely to be placed, for example, on Capital Radio in London. Similarly, location can have an impact on recruitment. Young volunteers are in good supply in London, but researchers who need elderly trial participants might do better going to Bournemouth.

Although altruism may be the motivating factor for some volunteers, it is reasonable to say that most do it for the money. Dr Amin agrees: "We shouldn't make any bones about it — people volunteer because they get paid. And rightly so, because the key element in phase I healthy volunteer trials is that they are not taking part because they are likely to get any benefit from the drug itself." But Dr Amin is keen to stress that volunteers are not being paid to act as guinea pigs. "They are being incentivised for the time that they are spending in taking part in the trial and the inconvenience that it's causing," she says.

The trial sponsor and investigator will jointly make the decision about how much volunteers are paid. An ethics committee will then review the level of payment to make sure it is appropriate. Payment levels tend to be based on an hourly rate set on a par with relatively low paid manual work. "You don't want to make it so attractive that people give up doing anything else and spend all their time doing trials. Equally you don't want to ask someone to do something without adequately compensating them," says Dr Amin.

Recruitment of patients

Tom Ruane is director of investigator services, patient recruitment and retention, at Quintiles, an international contract research organisation. He says that recruitment of patients for clinical trials is becoming more competitive. Figures show that only between 5 and 10 per cent of eligible patients actually become involved in a clinical trial. This means competition is fierce and results in trial units expending a considerable amount of time and energy in recruiting and retaining participants.

"Traditionally, patient recruitment amounted to patients turning up at their doctor in the normal course of treatment for their condition. Nowadays, recruitment is more complex so there are increasing requirements around raising awareness with patients," says Mr Ruane.

It stands to reason that the rarer the condition the more difficult it is to recruit patients. The trials exclusion criteria will make some people ineligible and there will be people who just say they do not want to take part. A spokeswoman for Aventis explains: "Clearly, the more rare the condition, the more centres you have to involve. We have just finished recruiting a trial based in France and the UK for a rare childhood malignancy. We had as many centres as we had patients."

The pharmaceutical industry can also find itself in a difficult position when doing trials in patients with drugs that have not yet reached the market. It cannot promote unlicensed drugs to the prescriber let alone to the patient. "What you have got to be careful of is not building up expectations in patients and actually advertising for a specific trial and a specific drug," she says. Normally, the first port of call is the prescriber/investigator who is doing the trial. They can then approach colleagues to refer patients to them or they may promote the fact that they are doing research in that disease to patient interest groups.

For some disease areas, especially the ones with strong interest groups or patient bodies, recruitment to trials is made easier because patients are well informed about what is going on in their particular disease area. Dr Richard Harvey, director of research, Alzheimer's Society, says one of the most recent trials in Alzheimer's disease — which involved an Alzheimer's vaccine — was so popular that patients were queuing up on the drug company's door step. "The trial was fully recruited with more than 350 patients within just over three weeks," he says.

For other diseases, trial units have to be more creative in the ways they inform patients. Some companies have raised awareness of urinary incontinence trials by placing advertisements on the back of toilet doors in hospitals. The advertisements ask patients if they have urinary incontinence and point out that there are trials investigating the best way of treating the condition. "We don't say we are doing a trial of this drug which may be the best thing since sliced bread, please contact our investigator. We do it much more obliquely, so as not to put prescribers in a difficult position."

Normally, patient volunteers are not paid for their involvment in trials. They will usually agree to take part because of the potential therapeutic benefits of the intervention being tested.

Patient groups

Mr Ruane, of Quintiles, says that patient groups have traditionally been nervous about being seen to endorse either drug companies or a product. However, they are starting to see the benefits of raising awareness about trials and of dispelling some of the negative publicity that has surrounded clinical trials.

Patients and healthy volunteers are probably more clued up about clinical trials than they have ever been. This means they are more questioning and more demanding than they have been in the past. The research industry has to be able to respond to this increased level of sophistication, says Mr Ruane. "Often patients know as much about their condition as the medical staff," he says.

He adds that by promoting awareness of clinical trials in general, patients are in a better position to make an informed decision about taking part in a trial.

The clinical research industry tends to inform patient groups about trials through focus group meetings, scientific meetings and through direct contact outlining initiatives.

Sheila Scott, the national education manager for the Parkinson's Disease Society, says the society is often asked to provide names of patients for trials by academic bodies, the pharmaceutical industry, manufacturers and small businesses. However, it does not give out names under any circumstances.

"In the case of society-funded research we may offer to put a letter from the researcher in the membership quarterly magazine, this informs our members but allows them freedom of choice," she says.

For small research initiatives the society suggests that researchers write to the society's local branches informing them of the trial details and leaving contact and choice to the branch individuals.

"The branches get many requests mirroring the national demand." However, Ms Scott points out that in many cases patients who are members of the society are not representative of those with Parkinson's disease as a whole. "They have sought information and support and in many cases, because of their contact with us, are extremely informed," she says. And depending on the nature of the trial, such patients may skew the patient population.

Safeguards for volunteers and patients

Safeguards for healthy volunteers are strict and the industry is heavily regulated. Trial units are required to comply with guidelines on good clinical practice, good laboratory practice and good manufacturing practice. "There are endless audits to ensure that everything is being done to maintain the subject's safety and data integrity," says Dr Amin. Volunteers are continually monitored and reams of safety data are generated. "The environment in which we do these studies is just one step down from an intensive care unit," she adds.

Safeguards for patients are similar to those for healthy volunteers, says Dr Ruane. "There are firewalls built into every step to ensure that the patient is protected at all times. This is monitored and audited intensively. And in terms of patient recruitment, strategies fall under the same regulations."

Is there anything to stop volunteers and patients taking part in more than one trial? Checks are made to ensure that healthy volunteers are not taking part in trials continuously. The volunteer's general practitioner is contacted and a volunteer's details are entered into a database so that a trial unit can tell if the person has taken part in a trial previously.

The procedure is slightly different for patients recruited into clinical trials. Their GP is informed that they are taking part in a trial and patients would not be recruited without the investigator seeing their clinical notes. If they are taking part in another trial or have done so before, the details will appear in their notes. In addition, most pharmaceutical companies would supply their investigators with a sticker to put on the notes to say the patient is taking part in a trial. "It alerts anyone involved in the care of that patient," the Aventis spokeswoman says.

Pharmaceutical companies are also required to carry indemnity policies so that patients and volunteers can be compensated for injuries incurred during a clinical trial.

"The intention is that if anything amiss happens to somebody, regardless of whether there is any fault from the product, they should be taken care of," she says.

Dr Harvey of the Alzheimer's Society agrees that regulations governing clinical trials means that patients are generally well protected. "There has been an enormous amount of work done by the academic and pharmaceutical community on the design of clinical trials and they are nearly all done to high standards. Trials for dementia are based on principles developed over the past 10 to 15 years which means you have to measure multiple domains to establish effectiveness, trials have to be long term, have to have an independent data monitoring committee, independent steering committee, full ethical approval and careful attention to safety. All of those things safeguard patients." He adds that when things do go wrong, monitoring committees ensure that trials are stopped quickly.

Steve Lawrence, chairman of Biotrax, a volunteer support group (see Panel), believes that when it comes to clinical trials the UK has the safest set of rules and regulations in the world. However, he is adamant that more attention needs to be paid to the rights of volunteers. "The guidelines mean that most medical volunteers are extremely safe in this country but that doesn't mean that they aren't at risk," he says.

"Volunteers need to be properly informed and educated. It's not uncommon for clinical trial units to brush over the less attractive detail of a trial because it's their objective to get as many volunteers as they can."

Mr Lawrence says volunteers sometimes contact Biotrax to find out whether a particular trial will be safe. "We can't tell volunteers that the drug being tested is actually going to be effective, not cause an adverse reaction or not have a significant risk attached to it. "We help people look at things from a realistic perspective and help them make their own decisions," he explains.

Although he does not believe that the rewards offered to volunteers are too high, Mr Lawrence is concerned that people may overlook the risks involved when deciding to take part in trials. "If a volunteer is willing to stay in a clinic for a month they can earn up to £3,500. If they do a weekend study they can earn up to £700," he says.

When amounts like these are discussed, it is not surprising that people who are strapped for cash see volunteering for trials as a way to solve their financial difficulties.

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