Emergency Research Ethics

Volume IV

A.M. Viens

• Publisher: Routledge
• Year: 2017
• Print ISBN: 9781409446811
• eBook ISBN: 9781351940634
• Topic: Diritto
• Subtopic: Diritto pubblico

The essays selected for this volume focus on issues that arise when attempting to design, review and undertake research involving human participants who are experiencing a private or public emergency. The main themes discussed by the essays are: the distinctive and significant ethical questions as to how research participants can be treated during emergency settings; the ethical challenges raised by emergencies for researchers undertaking research and its effects on the nature of research pursued; and procedural obstacles raised by emergencies which can affect the quality of good research ethics review. The volume is unique in that it is the first collection to exclusively deal with all of the central ethical aspects of conducting human subject research in the context of emergency.

Part I
Consent

[1]
Informed Consent in Emergency Research: A Contradiction in Terms

Malcolm G. Booth

Abstract Improving the treatment of life threatening emergency illness or disease requires that new or novel therapies be assessed in clinical trials. As most subjects for these trials will be incapacitated there is some controversy about they might best protected whilst still allowing research to continue. Recent European and UK clinical trials legislation, which has effectively stopped research into emergency conditions, is discussed. Possible changes to these regulations are proposed.

Keywords Ethics ⋅ Emergency research ⋅ Consent

Introduction

Medical research involving patients and healthy volunteers is required to enable new therapies to be evaluated prior to their widespread introduction. In order to protect the research subjects all research is performed within a strict framework of guidelines and regulations. Part of that framework is the requirement for a participant’s informed consent to be obtained before any part of the research protocol is commenced.

The pre-eminent importance of the individual’s consent reflects the importance given by society to the concept of individual autonomy, or self-determination. First highlighted in the Nuremberg Code, it has been re-emphasised most recently by the World medical Association in its latest version of the Declaration of Helsinki [1,2].

Under the current Governance Arrangements for Research Ethics Committees (GAfREC) in the UK potential trial participants are invited to consider participating in research [3]. This involves both verbal and written information. Subjects must normally be allowed at least 24 h to consider participating; be informed of reasonably foreseeable risks or discomfort; have the opportunity to ask questions, and only then is consent obtained. Of prime importance is that the subject is told that participation is voluntary and may withdraw his or her consent at any time without detriment.

An earlier version of this article was presented at The 7th International Conference on Bioethics on “The Ethics of Research in Emergency Medicine”, held on June 2, 2006, Warsaw, Poland.

M. G. Booth (

)

Anaesthesia and Intensive Care, Royal Infirmary, Castle Street, Glasgow G4 OSF, UK e-mails: [email protected]; [email protected]

There are, however, 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 situations need for immediate treatment means that consent cannot be obtained. Omitting consent is justified on the grounds of immediate necessity. New therapies for these life-threatening conditions must still be evaluated within a research framework whilst also ensuring that the novel treatment can be administered with minimal delay. Where the potential participant is unconscious, or otherwise incapacitated, the “normal” consent process cannot apply as their consent to participate in the trial cannot be obtained.

The CRASH¹ Trial, which investigated the effect of corticosteroids in head injury, is an example of the type of emergency research that requires recruitment before it is possible to obtain the patient’s consent [4]. Limited human data suggested that the steroids were beneficial in acute head injury and their use was standard practice in many neurosurgical units in the USA. Steroids were used to a more limited extent in the UK. The trial, which required patients to be recruited and treated within 8 h of injury, actually demonstrated that the administration of corticosteroids for acute head injury led to an increased mortality compared to those patients not receiving steroids. Consequently the CRASH trial led to a marked change in the treatment of head injury with a move away from steroids. Although few would argue that research such as the CRASH Trial should not be performed, there is much debate about how similar research can be performed within an acceptable legal and ethical framework which both protects the subject yet permits appropriate and necessary research.

Different approaches to obtaining consent for emergency research, such as prospective consent and deferred consent have been proposed and are outlined below. Both have been tried but with mixed success and have some have serious limitations.

Prospective Consent

Conceptually, prospective consent is the simplest approach to ensuring that informed consent is obtained from research subjects. It depends upon identifying a discreet ‘at risk’ population and obtaining consent from as many of them as possible before any emergency situation arises. Thereafter, as each person in the ‘at risk’ group presents with the emergency condition they can be entered into the study. There are, however, a number of problems associated with this approach.

The biggest difficulty is recruiting sufficient numbers of the ‘at risk’ group to ensure that enough will present with the emergency condition of interest. For example, if there is a 1% chance of the emergency condition arising and 100 subjects are required then it will necessary to consent 10,000 people. This is a virtually impossible task.

Given that any individual is unlikely to actually develop the emergency condition of interest will their consent be truly informed consent? Will they all give the risks of participation due consideration? Or will they volunteer, when they would not otherwise, because the chance of actually being in the trial is so low they give little thought to the potential consequences. There must also be a robust mechanism for differentiating those who have consented from those who have either refused or have not been approached.

Another issue to be addressed is the Hawthorne Effect, where a person’s behaviour may be influenced purely by the act of observing that behaviour. This may be beneficial, as in Eckman et al’s observational study of the use of antiseptic hand rub where compliance with infection control recommendations increased during the observation period [5]. Alternatively, subjects who have been told about their risk of developing a particular emergency condition may unconsciously alter their behaviour to reduce this risk. This could make recruiting sufficient subjects even more difficult.

Deferred Consent

An alternative approach is to accept that prospective consent for emergency research is not feasible and, therefore, to recruit patients without consent. Consent is then obtained at some point later from either the patient or a legally authorised representative (or proxy). Obviously any consent can only be for continued participation in the trial. Everything that has happened up to that point has already occurred so asking for consent retrospectively is meaningless. After all you cannot refuse, or consent to, something that has already happened. Unfortunately a number of patients will not survive to the point of being able to discuss their participation. Under these circumstances, or if no proxy is available, what should be done with the data collected up to that point? Can it be used or should it be destroyed? It would seem sensible to allow it to be kept for inclusion in the analysis, otherwise there is a significant risk of introducing considerable bias.

Proxy Consent

The Patient Self-Determination Act and the Adults with Incapacity (Scotland) Act have introduced, in the USA and Scotland respectively, the principle of allowing a proxy to act on behalf of an incapacitated patient [6, 7]. In both cases the proxy is authorised to decide about both routine care and recruitment to research protocols.

Exactly how good a proxy is at representing the wishes of the incapacitated person is open to question. The proxy is expected to make the decision that the incapacitated person would have made if he or she had been capable to do so. To be an effective proxy requires a level of knowledge about the patient’s wishes and values that few possess. Sulmasy found that the level of agreement between patients and their delegated proxy ranged from 57% to 81% [8]. Rates of agreement were not related to time that the patient and proxy had been together or whether the patient had an advance directive. The only factor that predicted the accuracy of the proxy’s decisions was whether the patient and proxy had ever discussed the patient’s wishes. A systematic review by Shalowitz et al even cast some doubt on how well previous discussion improved the proxy’s ability to act in the interests’ of the patient [9].

With emergency research comes the additional problem of the proxy’s being immediately available when needed. Even if on hand, the proxy’s ability to make an informed decision in the necessary time frame may be compromised by concern about the patient. This probably applies equally to urgent treatment decisions as much as it does to research.

That a proxy decision maker can be helpful under certain circumstances has been recognised by its introduction into European law by recent legislation. Unfortunately this legislation has also, in many peoples’ opinion, actually confounded the difficulties in performing of emergency research by coincidentally introducing further obstacles.

Emergency Research in Europe

Directive 2001/20/EC was intended to approximate the regulations governing medical research across the member states of the European Union thereby making research more uniform across the Union [10]. Article 5 which covers research involving incapacitated adults itemises a number of criteria that must be fulfilled prior to recruitment of an incapacitated adult to a research project. Prior to the publication of the Directive the approach to emergency research had been largely pragmatic. That is, it was accepted that incapacitated subjects could not provide consent, legally no one could either, but the research needed to be done so patients were enrolled into research. This was done with the best of intentions but did not provide appropriate protection and oversight for either the subject, or the researcher.

The directive reiterates the need for prior informed consent before individuals can be recruited to research trials. There is no exception in the case of emergency research but consent can obtained from a legal representative. As mentioned already there are several problems with using a proxy in these circumstances. The Directive does not give a clear definition of who may act as the legal representative.

It is also proposed that the planned research must relate directly to the life threatening or debilitating clinical condition affecting the incapacitated person. This caveat is, presumably, intended to prevent vulnerable people being recruited to trials when there is a suitable alternative group who would be capable of providing informed consent. Unfortunately, by inference this requirement also excludes investigation of other supportive therapies necessary for the treatment of the underlying condition. In some instances this secondary treatment can be almost as important as the main treatment for a particular condition, e.g. ventilation strategies following traumatic head injury.

Before the trial starts there must also be grounds for expecting that the trial product will produce a benefit to the patient, outweighing its risks or be of no risk at all. There is no guidance as to how st...

Table of contents

• Cover Page
• Title Page
• Copyright Page
• Table of Contents
• Acknowledgements
• Series Preface
• Introduction
• PART I CONSENT
• PART II EMERGENCY AND CRITICAL CARE MEDICINE
• PART III VULNERABLE POPULATIONS
• PART IV PUBLIC CONSULTATION AND PERCEPTION
• PART V GOVERNANCE AND REGULATION
• PART VI PUBLIC HEALTH EMERGENCIES
• PART VII COMPLEX AND HUMANITARIAN EMERGENCIES
• Name Index