Medical research involving patients and healthy volunteers is required to enable new therapies to undergo a process of evaluation prior to their widespread introduction. In order to protect the research subjects all research is carried out within a framework of guidelines and regulation. Part of that ethical and legal framework is informed consent, which is a prerequisite for recruiting to a research protocol.
There are a number of clinical situations, such as cardiac arrest, multiple trauma and major head injury, which present as life-threatening emergencies necessitating immediate treatment. In these cases consent for treatment cannot be obtained so immediate treatment is justified on the basis of immediate necessity. Clinical trials of new, or alternative, therapies for similar life-threatening conditions, whilst requiring the same level of evaluation as any other new therapy, also require that the novel treatment be administered with minimal delay. In these circumstances the potential subjects are unconscious or otherwise incapacitated and cannot therefore consent to participate in a trial. Likewise treatment cannot be delayed whilst a relative or other legal representative is found.
The CRASH Trial (controlled trial of corticosteroids after significant head injury) investigating the effect of corticosteroids in head injury is an example of the type of emergency research that requires recruitment without the consent of the participant . To be eligible for the trial the patient had to have a reduced level of consciousness rendering them unable to consent. Treatment needed to begin within 8 h, or less, for it to have the postulated benefit. Although few would argue that such research should not be performed, there is debate about what preconditions are necessary to ensure its acceptability both legally and ethically. Such a list of preconditions has previously been proposed by Lötjönen .
Despite the importance of emergency research there has been little discussion about the view of the public on recruitment to emergency research in the UK or how the issues around consent might be resolved. This study, therefore, aims to assess the attitudes of the public to consent for emergency research.
In order to ascertain the perception of the public to emergency research, patients attending the outpatient department of a university teaching hospital were invited to complete a self-administered questionnaire (Appendix 1). Institutional Research Ethics Committee approval was obtained and all participants gave written informed consent. Over a 5-week period, two medical students (AL and ER) approached patients attending the outpatient department of a university teaching hospital. Subjects were selected from a variety of medical and surgical clinics but were not screened prior to being invited to take part in the study.
Three hundred and seventy patients were approached. Seven patients agreed to complete the questionnaire but were called into their clinic before they had started and two others were unable to read the questions because they did not have their reading glasses with them. Three hundred and sixty-one questionnaires were therefore completed and analysed (98% response rate). Of the three hundred and sixty-one respondents 84% thought emergency research should be started in the absence of any consent. If the research had started 82% thought that consent should be obtained as soon as possible from the nearest relative and 90% thought that, if possible, it should also be obtained from the patient. If the relative or patient refused consent 62% felt the information gathered up to the time of refusal should still be used, as did 81% if the patient died before consent had been obtained. Despite 62% approving of public meetings to inform the public of emergency research activity only 35% said they would consider attending such a meeting.
The list of possible preconditions for emergency research as suggested by Lötjönen was generally approved . These were no other consentable group (47%), no method of advance consent possible (55%), unable to delay treatment (73%), consent to be obtained as soon as possible (88%), an adequately designed protocol (74%), Ethics Committee approval (71%), patient may benefit (85%), future patients may benefit (92%), the treatment being investigated is necessary and cannot be delayed (91%).
The majority (92%) of respondents were willing to be recruited to an emergency research protocol if there were minimal risks involved and 67% if the risks were moderate.
Emergency research must be performed to improve the treatment and outcome from life-threatening illness or injury. This study suggests that the majority of this sample of the public is aware of the importance of this type of research and accepts that the normal rules of consent cannot be applied. The finding that 84% of those surveyed would permit emergency research without prior consent is comparable to the 70-80% of the public who support organ donation .
A criticism of this study is the use of people attending the outpatients department, which could introduce bias, as they may not be a true representation of the general public. It could be argued that an outpatient has a greater interest in research being performed than someone with no hospital contact. Ideally, therefore, this study should have been performed outside the hospital environment. Due to resource limitations pragmatism required that the study be based in the outpatients department. Most people will have had contact with a hospital in one form or another so consequently any differences between the study population and the general public may be of little practical significance.
Consent for emergency research has to be obtained within the framework of the guidelines from the appropriate statutory bodies. This provides protection for the patients or subjects, the relatives and the researchers. In the UK the General Medical Council has issued guidelines to doctors. In addition recent legislation in Scotland now specifically permits proxy decision-making and it is possible that legislation in the rest of the UK may follow similar lines. From May 2004 new European legislation on the conduct of research has also applied in the UK .
The current guidance from the General Medical Council recommend that in an emergency where consent cannot be obtained, treatment can be given only if it is limited to what is immediately necessary to save life or to avoid significant deterioration in the patient's health. This may include treatment that is part of a therapeutic research project, where the risks of the new treatment are not believed to exceed the known risks of standard treatment. If, during treatment, the patient regains capacity then the patient should be told about the research as soon as possible and their consent to continue should be sought. If it is possible, the situation should be discussed with relatives and/or partners of the patient and a valid advance refusal should always be followed. If there is time, the recruitment of the incapacitated patient should be discussed with another member of the research team .
The European Union Directive on Good Clinical Practice in Clinical Trials (Directive 2001/20/EC) became law in the UK in May 2004 . The Directive's intention is to simplify and harmonize the regulations governing clinical trials across Europe and so allow more co-ordination of trials across the EU. Article 5 of the Directive addresses clinical trials involving incapacitated adults unable to give informed consent. The first such precondition to any clinical trial is that informed consent of the person's legally authorized representative be obtained. This immediately creates a problem, as many countries (including England and Wales) have no provision for such proxy consent. Even in countries, such as Scotland, that permits proxy consent the same problem arises for emergency research. Time constraints often do not allow for the representative to be consulted or, if available, they may be too distressed to process and assimilate the information necessary to provide valid consent. It therefore appears that one effect of implementing the European Directive may be to hinder emergency research.
Where proxy consent cannot be applied alternative approaches to consent in emergency research have been attempted. Prospective consent is the simplest of these. If an ‘at risk’ group of potential subjects can be identified and recruited, in advance of any illness or disease developing, no time need be wasted once they present with the illness being studied . The advantage of prospective consent is it allows time for the potential recruit to ask questions and have them answered. There are, however, disadvantages to this approach. The researcher is dependent on sufficient numbers of the consented group developing the emergency condition being studied. There also needs to be a method of immediately and accurately identifying those people who have consented to participate from those who have not. Finally, as the likelihood of any individual actually entering the trial is small it may be necessary to consent hundreds, if not thousands, of potential subjects in order to have sufficient participants.
Another alternative approach is to defer obtaining consent until the person is fit to provide it. Thus the person is recruited to the trial protocol without any permission being sought and is only asked for consent once sufficient capacity has returned. Consent cannot be given or refused for events that have already happened, however, consent can only be for continued participation.
It has been argued that consent may not always be necessary . Emergency research is vitally important to society because all new therapies, including those for emergency treatments, must have their efficacy established before becoming accepted practice. In 1996 the Food and Drug Administration published guidelines for emergency research in the USA which allow subjects to be recruited without their consent. To compensate for the subjects' inability to provide consent additional protection is given for the subject and emergency research is permitted in the USA but only within strict guidelines .
In conclusion, emergency research must occur to improve the outcome from life-threatening illness or injury. The majority of respondents in this survey appear aware of the importance of this type of research and accept that the normal rules of consent cannot be applied. Most were willing to be recruited to an emergency research trial without their consent should the eventuality arise.
1. MRC CRASH Trial National Coordinators. Update on progress in the international, multicenter, randomized, controlled trial of corticosteroids after significant head injury. Curr Opin Crit Care
2. Lötjönen S. Medical research in clinical emergency settings in Europe. J Med Ethics
3. British Medical Association. Organ donation in the 21st century: time for a consolidated approach. www.bma.org/ap.nsf/Content/organ+donation+in+the+21st+century
4. European Union Directive 2001/20/EC on Good Clinical Practice in Clinical Trials. Off J Eur Commun
5. General Medical Council. Guidance on good practice. http://www.gmc-uk.org/standards/default.htm
6. Olson CM. The letter of the spirit; consent for research in CPR. JAMA
7. Biros MH, Lewis RJ, Olson CM, Runge JW, Cummins RO, Fost N. Informed consent in emergency research: consensus statement from the coalition conference of acute resuscitation and critical care researchers. JAMA
8. Nightingale SL. Exception from informed consent requirements for emergency research (from the Food and Drug Administration). JAMA
Public perception of emergency research
Please read the questions and answer them to the best of your ability.
It is normal practice to when inviting a person to take part in a research project to obtain their consent for their inclusion in the research. Most research consists of comparing the standard treatment with a new treatment to see if the new treatment is as good, or possibly better, than the standard therapy.
Some forms of emergency treatment need to be started immediately with no time for discussion with the patient. The patient under these circumstances is too unwell, even unconscious and therefore unable to make a decision about treatment. The doctor, under these conditions, will start life saving treatment without the patient's prior consent. Research intending to improve the treatment of these life-threatening conditions also needs to be started as soon as possible, often before a relative can be found with whom to discuss the patient's wishes about research. This often referred to as emergency research.
Some examples of emergency treatment where treatment or research protocols would need to be started immediately are:
- Treatment of cardiac arrest (where the heart has stopped).
- Immediate treatment of severe trauma/injury including head injury.
There is controversy as to whether emergency research should be permitted because the research subjects are recruited without their permission. To our knowledge no one has attempted to discover the views of the public in the UK on this. The purpose of this questionnaire is to ask you your views on emergency research.
1. Do you think that emergency research, where treatment has to be started before consent can be obtained from the patient or a relative, should be allowed? Yes / No / Don't know
2. Once the research protocol has started should a relative be able to consent to the person's continued involvement? Yes / No / Don't know
3. If the patient's condition improves enough should their consent be requested for their continued involvement? Yes / No / Don't know
4. If the patient's condition improves enough should their consent be requested for being included in the research project up to this point? Yes / No / Don't know
5. If the patient decides not to grant consent to having been recruited what should happen to the research data gathered from that patient? (please circle)
- It should be used in the analysis anyway but no further information gathered.
- The information should be destroyed.
- Don't know.
6. The serious nature of illnesses or injury requiring immediate treatment is such that a number of patients will die despite the treatment. Should the information obtained from any that die, even if they never gave consent, be used as it may help clarify which treatment is better? Yes / No / Don't know
7. In the USA one of the preconditions for allowing emergency research is that the group of people likely to be used in the research study is informed in advance of the study starting. This requires a series of advertisements (TV and radio), public meetings and other activities to publicise the research. Do you think that this would be practical way forward in this country? Yes / No / Don't know
8. Would you attend such a meeting? Yes / No / Don't know
9. A number of preconditions to doing emergency research have been suggested and are listed next. Do you agree or disagree with the following?
10. Imagine you are extremely ill from, for example a heart attack, a stroke or a head injury. There is a research project looking at ways of improving the treatment of this illness. You are too ill to give your consent to being recruited to this research. Would you accept being recruited to it if:
- — there is little or no risk to you and the research only required one or two extra blood samples to be taken. Yes / No / Don't know
- — there was a moderate risk in taking part in the research but the results might improve the outcome for patients in the future. Yes / No / Don't know
Thank you for completing this questionnaire.