The UK Debate over Recruitment Strategies

When it comes to subject recruitment, every clinical trial professional faces a grave dilemma: Suitable individuals who meet the study criteria clearly need to be informed about the benefits of taking part in a trial, but to what extent is it appropriate for an investigator to actively urge people to participate in clinical research? In other words, when does acceptable encouragement become harassment?

Jenny Hewison, Professor of the Psychology of Health Care, Institute of Health Sciences and Public Health Research, the University of Leeds

This ethical dilemma is particularly acute in the United Kingdom, where government-owned hospitals in the National Health Service (NHS) provide around 90% of health care. Investigators must adhere to strict regulations. They cannot advertise for subjects because that is regarded as an inducement, and they are not supposed to refer to favorable results or publicity because that is viewed as promoting the research cause. Posters in clinics can indicate that a trial is taking place and investigators can obtain publicity by giving media interviews, but more overt methods are not permitted.

An article in the British Medical Journal has added fuel to this hotly contested issue.¹ The authors suggested that the practices of ethics committees in the UK are hindering subject recruitment. Lead author Professor Jenny Hewison from the Institute of Health Sciences and Public Health Research at the University of Leeds recently shared her views with Philip Ward, ACT's European Editor.

Q. In what ways are current research ethics requirements compromising the scientific quality of health research?

A. The problem I am most aware of relates to restrictions on how researchers may approach potential participants, and the effect those restrictions are having on recruitment rates and bias.

For instance, let's say you get a letter from your general practitioner or hospital doctor giving information about a research project in which you might participate. Under the so-called opt-in system, the letter will make it clear that it is up to you to contact your doctor to say the researchers may contact you. You may also contact the research team directly. In contrast, under an opt-out system, the initial letter will explain that a researcher will contact you, usually by phone, unless you tell your own doctor that you do not want to be contacted, in which case your name will never be given to the researchers.

In the UK, a trial to compare recruitment rates under the two systems cannot be conducted because one of the "treatments"—having to opt out of initial contact—is considered unethical. The best evidence we have for an effect comes from other comparisons of survey response rates, supported by a large methodological literature on factors affecting response and participation rates in research of different kinds.

In many cases, trial participation rates seem to be falling. This may be due to attitudes toward "volunteering," an understandable lack of public awareness about the importance of response rates, incorrect assumptions about what research entails, and just plain inertia. We do not have the evidence to know for certain.

Q. Are you also suggesting that only the researcher should deal with consent forms and the patient?

A. No, because opt in and opt out do not refer to participation in the research, only to being contacted by a researcher. Under both systems, the researcher seeks informed consent for participation in the research in the usual way.

Information and consent forms have always had to be approved by the relevant ethics committee, under both systems. For good reasons, these documents have to be simply written and brief. They cannot possibly provide answers to all the questions that potential participants may wish to ask. A conversation with a researcher provides an opportunity for people to ask the questions that matter to them.

Is such a conversation also a vehicle for talking somebody into something to meet a recruitment target? That is not as tempting as you might think. Signing up people who vote with their feet and drop out of the study soon afterward is a waste of everybody's time. Such practices would show up in retention rates, and corrective action would be taken.

Q. In the BMJ article, you recommend that all patients are told about the potential use of personal information for research and that a strategy is needed to inform people about how research can contribute to improved health care. What exactly should patients be told, and how should this information be disseminated and written for the public?

A. Members of the public value health research but probably have a limited idea about the kinds of activities that are encompassed by it, and an even more limited idea about the kinds of things that threaten research quality. In the UK, the NHS could publicize much more strongly that it needs and values many different kinds of high-quality research because of the benefits it brings to patients. Publicity takes lots of forms, but with the right expertise, I am sure we could put together a good campaign if the will was there.

If everybody benefits from research, it can then be argued that everybody should be encouraged to at least consider taking part if invited. Provided proper accreditation and safeguards exist, researchers could approach NHS patients to discuss participation in relevant projects, unless the patient had specifically asked to be exempt. Detailed information would be provided as required, but the initial "headline" message to anybody using the NHS would be about the importance and value of research, and the importance and value of considering participation.

It would certainly help if investigators and sponsors were both involved in the campaign to raise and maintain the profile of research.

Q. Will your proposed changes add to the work of an investigator or raise confidentiality issues?

A. Overall, the changes would lead to less work for investigators. At the moment, potential participants have to be identified and approached, but a low recruitment rate means that a lot of work is wasted. Extra clinics may then be needed to meet recruitment targets, but adding clinics means extra paperwork. If the new clinics have the same low recruitment rate, then a dispiriting cycle continues.

To maintain confidentiality, NHS staff identify and make the initial contact with potential participants under both opt-in and opt-out systems. In theory, they could make telephone calls as well as send letters, but few have the resources to do that. To ask NHS staff to spend a lot of time on recruitment is also asking too much. The only people with both the time and the detailed knowledge to help people make informed decisions about participation are the researchers. If people who want 100% privacy can opt out, and if the researchers are vetted, accredited, and working to a tightly monitored protocol, then a balance can be struck between confidentiality and quality. We should explain to the public about the need for a trade off and consult with them about where they think the balance should lie.

Q. The serious adverse events in the Phase I trial conducted at Northwick Park Hospital caused widespread public concern in Spring 2006. What impact do you think this case will have on recruitment rates, both in the short and long term?

A. We expect recruitment rates to be affected, but we need to wait and see the figures. If recruitment falls, proper research would be needed into the reasons behind that. When referring to clinical trials, the press gives the wrong impression that they are all the same, but members of the public can distinguish between different kinds of interventions pretty well, given the right information. They also know that trains can crash and ferries can sink (i.e., disastrous things can happen), but the right response is to work very hard to ensure they don't happen again. I have even heard it said—by a participant—that now is a good time to enter clinical trials because investigators are going to be ultra, ultra safety conscious.

Q. What other general advice do you have about improving recruitment?

A. Recruitment is everybody's business, not just an investigator's. My best advice is to put yourself in other people's shoes and try to understand why someone might want to participate in a trial and what might put them off. A lot of it comes down to appreciating that before people decide what to do, they first try to make sense of being invited. Then they try to work out the implications for them personally. We need to help people carry out these tasks accurately and easily.

References

1. J. Hewison and A. Haines, "Overcoming Barriers to Recruitment in Health Research," BMJ 333, 300–302 (2006).