Forging convictions: The effects of active participation in a clinical trial

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Abstract

This qualitative study explored non-specific influences on participation in, and outcomes of, a randomised controlled trial. It was nested within a single-blind clinical trial of western acupuncture which compared real acupuncture with two types of placebo control administered to National Health Service (NHS) patients awaiting hip and knee replacement surgery in England. Data collection (2004–2008) was based on narrative-style interviews and participant observation. The results indicate that trial recruitment and retention depend on a set of convictions forged largely as a result of contextual factors peripheral to the intervention, including the friendliness and helpfulness of research centre staff and status of the administering practitioner. These convictions also influence the reporting of the study outcomes, particularly if participants experience uncertainties when choosing an appropriate response. The findings suggest that participants in clinical trials are actively involved in shaping the research process, rather than passive recipients of treatment. Thus the outcomes of trials, notably those involving contact interventions, should be regarded not as matters of fact, but as products of complex environmental, social, interpretive and biological processes. In this paper, we develop and present a ‘theory of active research participation’ which offers a framework for understanding the impact of non-specific processes in clinical trials.

Highlights

► Contextual effects influence recruitment, retention and outcome in randomised clinical trials. ► A new theory of active research participation explains these processes. ► Trial participants actively seek information and cues to support participation and form judgements about treatment outcome. ► Methods used to increase trial recruitment and retention enhance context effects and influence outcomes. ► All aspects of participant information and contact should be regarded as components of trial intervention.

Introduction

This study was designed to explore non-specific influences within a randomised controlled (clinical) trial (RCT). The term ‘non-specific’ refers to incidental contextual effects that are not specific to the intervention under investigation. Kaptchuk et al. (2008) divided these into three distinct theoretical components: responses to observation and assessment, responses to the therapeutic ritual (placebo), and responses to the patient–practitioner interaction. The double-blind RCT is designed to control for these influences and is thus regarded as the ‘gold standard’ (Jadad, 1998) and cornerstone of evidence-based medicine (Lambert, 2006). Three key factors used to judge the unbiased nature of an RCT are randomisation, double-blinding and withdrawals/drop-outs (Jadad et al., 1996). Provided the test and control interventions are comparable and attrition distributed evenly across groups, randomisation eliminates selection bias and controls for placebo effects. ‘Double-blind’ means that neither the patient, nor the attending practitioner, nor the researchers who analyse the data know which intervention the patient has received (Miller & Stewart, 2010). This eliminates what Jadad (1998: 32) termed ‘ascertainment bias’, which can lead to differences in practitioner/researcher expectations and behaviours, patient–practitioner interactions and patient responses. Blinding of the practitioner is only possible if the test and control treatments are indistinguishable at the point of administration, as in most drug trials. This is not possible when testing physical, surgical or psychological procedures, though scientific quality may be preserved if the control intervention is perceived by the recipient to be equivalent and the clinician’s performance is equally convincing. Bias may be detected by inviting the patient to guess which treatment they received, but there is currently little consensus about the best method of evaluating blinding in this type of context (Schulz, Altman, & Moher, 2010).

Our study focused on non-specific influences in a single-blind RCT of acupuncture. Researchers in complementary and alternative medicine (CAM) have come under increasing pressure to demonstrate scientific validity (Ernst, 2001). Western acupuncture has come under close scrutiny because it is widely practiced within conventional healthcare systems. The invention by Streitberger and Kleinhenz (1998) of a sham needle, creating the illusion of needle penetration, has afforded an effective placebo intervention and facilitated blinding of the recipient. However, the impossibility of blinding the practitioner has continued to render trial outcomes difficult to interpret (Langevin et al., 2006). For example, strong beliefs about therapeutic value may lead to subtle, if unintentional, variations in practitioner behaviour that bias treatment administration (Ross et al., 1999) and affect the therapeutic relationship (Paterson & Dieppe, 2005), with the result that isolating specific efficacy is problematic (Kaptchuk, 2002, Lewith et al., 2006). Against this background, our study sought to identify and explain the potential impact of non-specific treatment effects.

Section snippets

Study context

The qualitative study was ‘nested’ within a trial of acupuncture designed to control for potential sources of bias, including type of acupuncture placebo, patient expectations, practitioner empathy and treatment credibility (Lewith et al., 2009). Participants who had a diagnosis of hip or knee osteoarthritis were recruited from NHS (National Health Service) waiting lists for joint replacement at two district general hospitals in the UK. Out of 1472 patients approached, 221 consented and were

Method

Ethical approval for the qualitative study was given, as part of the trial, by Southampton and South West Hampshire REC A. Recruitment into the trial was slow and data collection extended from 2004 to 2008. In order to understand the processes which underpin non-specific influences, data collection and analysis were informed by the principles of grounded theory (Glaser, 2002), as detailed in the following sections. The data consisted of post-trial narrative interviews contextualised by field

Findings

Experiences of participation in the clinical trial were grouped into three emergent categories: ‘making a commitment’ (to the trial), ‘maintaining the commitment’, and ‘producing an outcome’. ‘Forging convictions’ reflected a dynamic process that underpinned all aspects of trial participation and was labelled as the core category. Each category is considered in relation to the extant literature. Pseudonyms are used throughout and we have identified details of the intervention received where

Conclusions

Based on our findings, we propose an explanatory theory which we have labelled the theory of active trial participation (Fig. 1).

Our theory suggests that individuals take part in clinical trials because of a combination of curiosity, altruism, the desire for some kind of personal gain, personal or vicarious experiences of the treatment under investigation and/or the status gained as a research participant. The convictions that draw them into the trial are strengthened during the research

Acknowledgements

The acupuncture trial and qualitative study were funded by a Department of Health Postdoctoral Research Award to Peter White. Additional funding was provided by the Rufford Maurice Laing Foundation and the Southampton Complementary Medicine Research Trust.

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