Lay public’s understanding of equipoise and randomisation in randomised controlled trials

EJ Robinson,^1* CEP Kerr,¹ AJ Stevens,² RJ Lilford,² DA Braunholtz,² SJ Edwards,³ SR Beck⁴ and MG Rowley¹

¹ Department of Psychology, Keele University, UK
² Department of Public Health and Epidemiology, University of Birmingham, UK
³ Centre for Ethics in Medicine, University of Bristol, UK
⁴ School of Psychology, University of Birmingham, UK

* Corresponding author

Objectives

To understand why, despite efforts to make trial information clear, participants in RCTs are at risk of failing to take in or remember information about random allocation and equipoise.
To investigate the background knowledge about randomisation and equipoise that members of the public are likely to bring to bear if invited to take part in an RCT.
To explore in the context of hypothetical trials the effects of providing information designed to overcome barriers to understanding and recall of randomisation and equipoise.

Methods

Reviews

The investigations were informed by an update of an earlier systematic review on patients’ understanding of consent information in clinical trials, and by relevant theory and evidence from experimental psychology.

Investigations

Nine investigations were conducted, involving healthy adult participants with a wide range of educational backgrounds and ages. Use of hypothetical scenarios allowed precise comparisons to be made between conditions in ways that would be both impractical and unethical in real clinical settings, but which could produce results relevant to real trial consent procedures. Investigations 1–6 (n between 67 and 130) examined participants’ background assumptions concerning equipoise and randomisation. Investigations 7–9 (n = 128) explored ways of helping participants to recognise the scientific benefits of randomisation.

Results

Reviews

Recent literature continues to report trial participants’ failure to understand or remember information about randomisation and equipoise, despite the provision of clear and readable trial information leaflets. Within the context of research in experimental psychology this is unsurprising. Patients’ expectations about normal treatment decisions may make it hard for them to take in information about randomisation and equipoise. Even if patients realise that normal treatment decision-making is not going to take place, they may lack appropriate scientific background knowledge to interpret trial information as intended. In current best practice, written trial information describes what will happen without offering accessible explanations. As a consequence, patients may create their own incorrect interpretations and consent or refusal may be inadequately informed.

Investigations

Investigations 1–6 addressed the following questions.

Do members of the public understand and accept randomisation?
In investigation 1, participants judged which methods of allocation were random. The majority judged correctly. However, most judged the random allocation methods to be unacceptable in a trial context.
Do members of the public assume that new treatments are better?
In investigation 2, the mere description of a treatment as new was insufficient to engender a preference for it over a standard treatment.
Do they accept doctors’ individual equipoise?
In investigations 3 and 6 around half of the participants denied that a doctor could be completely unsure about the best treatment.
Do they accept doctors’ suggestions of random allocation given equipoise?
In investigations 3 and 6, a majority of participants judged it unacceptable for a doctor to suggest letting chance decide when uncertain of the best treatment. Randomising for research purposes may be judged less unacceptable.
Do they believe that random allocation has scientific benefits?
In investigations 4–6, in the absence of a justification for random allocation (none is currently recommended for real trial information leaflets), participants did not recognise scientific benefits of random allocation over normal treatment allocation methods: they failed to judge that doctors would be more sure about which of two treatments was better when allocation was at random rather than by doctor/patient choice.

Investigations 7–9 examined the consequences of explaining the reasons for randomising. In investigation 7 a pre-existing brief justification for randomisation did not help participants to recognise the scientific benefits of random allocation. With more demanding procedures used in investigations 8 and 9, both this brief justification and an extended explanation led participants to recognise that more certain knowledge would arise with random allocation than with doctor/patient choice. The pattern of results across investigations 7–9 suggests that merely supplementing written trial information with an explanation is unlikely to be helpful. However, when people manage to focus on the trial’s aim of increasing knowledge (as opposed to making treatment decisions about individuals), and process an explanation actively by answering test questions, they may be helped to understand the scientific reasons for random allocation.

Conclusions

This research was not carried out in real healthcare settings. However, participants who could correctly identify random allocation methods, yet judged random allocation unacceptable, doubted the possibility of individual equipoise and saw no scientific benefits of random allocation over doctor/patient choice, are unlikely to draw upon contrasting views if invited to enter a real clinical trial. This suggests that many potential trial participants may have difficulty understanding and remembering trial information that conforms to current best practice in its descriptions of randomisation and equipoise.

Given the extent of the disparity between the assumptions underlying trial design and the assumptions held by the lay public, the solution is unlikely to be simple. Nevertheless, the results suggest that including an accessible explanation of the scientific benefits of randomisation may be beneficial provided potential participants are also enabled to reflect on the trial’s aim of advancing knowledge, and to think actively about the information presented.

Recommendations for research

The findings of this study raise the following questions:

How is participants’ understanding of written trial information influenced by different forms of oral accompaniment? A leaflet may be understood and remembered more or less well depending on what is said during recruitment. Effective combinations of written and oral information need to be identified.
How can potential trial participants be helped to take a research perspective and thereby improve their chances of understanding about random allocation and equipoise? Participants tend to construe a trial as aiming to identify the best treatment for each recruit. Informed decision-making may be more likely if participants can reflect on the aim of advancing knowledge.
Can (and should) research ethics committees expect trialists to have evaluated information leaflets on relevant patient groups? The current emphasis is on leaflets’ adherence to national guidelines. An evidence-based approach to leaflet construction may be valuable.

Publication

Robinson EJ, Kerr CEP, Stevens AJ, Lilford RJ, Braunholtz DA, Edwards SJ, et al. Lay public’s understanding of equipoise and randomisation in randomised controlled trials. Health Technol Assess 2005;9(8).

NHS R&D HTA Programme

The research findings from the NHS R&D Health Technology Assessment (HTA) Programme directly influence key decision-making bodies such as the National Institute for Clinical Excellence (NICE) and the National Screening Committee (NSC) who rely on HTA outputs to help raise standards of care. HTA findings also help to improve the quality of the service in the NHS indirectly in that they form a key component of the ‘National Knowledge Service’ that is being developed to improve the evidence of clinical practice throughout the NHS.

The HTA Programme was set up in 1993. Its role is to ensure that high-quality research information on the costs, effectiveness and broader impact of health technologies is produced in the most efficient way for those who use, manage and provide care in the NHS. ‘Health technologies’ are broadly defined to include all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care, rather than settings of care.

The HTA programme commissions research only on topics where it has identified key gaps in the evidence needed by the NHS. Suggestions for topics are actively sought from people working in the NHS, the public, consumer groups and professional bodies such as Royal Colleges and NHS Trusts.

Research suggestions are carefully considered by panels of independent experts (including consumers) whose advice results in a ranked list of recommended research priorities. The HTA Programme then commissions the research team best suited to undertake the work, in the manner most appropriate to find the relevant answers. Some projects may take only months, others need several years to answer the research questions adequately. They may involve synthesising existing evidence or designing a trial to produce new evidence where none currently exists.

Additionally, through its Technology Assessment Report (TAR) call-off contract, the HTA Programme is able to commission bespoke reports, principally for NICE, but also for other policy customers, such as a National Clinical Director. TARs bring together evidence on key aspects of the use of specific technologies and usually have to be completed within a limited time period.

Criteria for inclusion in the HTA monograph series

Reports are published in the HTA monograph series if (1) they have resulted from work commissioned for the HTA Programme, and (2) they are of a sufficiently high scientific quality as assessed by the referees and editors.

Reviews in Health Technology Assessment are termed ‘systematic’ when the account of the search, appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others.

The research reported in this monograph was commissioned by the HTA Programmeas project number 98/23/20. As funder, by devising a commissioning brief, the HTA Programme specified the research question and study design. The authors have been wholly responsible for all data collection, analysis and interpretation and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the referees for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

The views expressed in this publication are those of the authors and not necessarily those of the HTA Programme or the Department of Health.

Editor-in-Chief: Professor Tom Walley
Series Editors: Dr Peter Davidson, Professor John Gabbay, Dr Chris Hyde, Dr Ruairidh Milne, Dr Rob Riemsma and Dr Ken Stein
Managing Editors:Sally Bailey and Caroline Ciupek

HTA Home Page | Details page for this publication | Publications listing | Publications search