A Practical Guide to Cluster Randomised Trials in Health Services Research

Sandra Eldridge, Sally Kerry

• Publisher: Wiley
• Year: 2012
• ISBN:
  9781119966722
• Edition: 1
• Topic: Medicina
• Subtopic: Medicina clinica

Cluster randomised trials are trials in which groups (or clusters) of individuals are randomly allocated to different forms of treatment. In health care, these trials often compare different ways of managing a disease or promoting healthy living, in contrast to conventional randomised trials which randomise individuals to different treatments, classically comparing new drugs with a placebo. They are increasingly common in health services research. This book addresses the statistical, practical, and ethical issues arising from allocating groups of individuals, or clusters, to different interventions.

Key features:

• Guides readers through the stages of conducting a trial, from recruitment to reporting.
• Presents a wide range of examples with particular emphasis on trials in health services research and primary care, with both principles and techniques explained.
• Topics are specifically presented in the order in which investigators think about issues when they are designing a trial.
• Combines information on the latest developments in the field together with a practical guide to the design and implementation of cluster randomised trials.
• Explains principles and techniques through numerous examples including many from the authors own experience.
• Includes a wide range of references for those who wish to read further.

This book is intended as a practical guide, written for researchers from the health professions including doctors, psychologists, and allied health professionals, as well as statisticians involved in the design, execution, analysis and reporting of cluster randomised trials. Those with a more general interest will find the plentiful examples illuminating.

1

Introduction

Cluster randomised trials are trials in which groups (or clusters) of individuals are randomly allocated to different forms of treatment. In healthcare, the different forms of treatment are sometimes different drugs or, more commonly, different ways of managing a disease or promoting healthy living. These trials are in contrast to conventional randomised trials which randomise individuals to different treatments, classically comparing new drugs with a placebo. Cluster randomised trials are common in health services research. This is an area of research concerned with the way healthcare is delivered and with measures taken to prevent ill health and encourage healthy living. It covers a broad range of topics and is an important area in maintaining high standards in a modern health service. New initiatives or interventions in health care may be evaluated by comparing health outcomes in those that are exposed to the new initiative with outcomes in those receiving usual care or an alternative intervention. Since interventions often need to be introduced to a whole organisational unit such as a general practice or geographical area, cluster randomised trials are often the best method of evaluating such interventions.

There are many books written about trials in general, which explain in detail the key features of the design, conduct and analysis of randomised trials; but these are mainly concerned with trials which randomise individual patients to different interventions (Pocock, 1983; Matthews, 2000; Torgerson and Torgerson, 2008). There are now three books that describe the design, analysis and conduct of cluster randomised trials: Murray (1998), Donner and Klar (2000) and Hayes and Moulton (2009). These books have mainly concentrated on large community trials. Hayes and Moulton have a particular emphasis on trials in low-income countries where whole communities have been randomised. Since we have extensive experience in health services research, in this book we have focused on cluster randomised trials in this area, though we have used other examples where useful. This book is intended as a practical guide, written for researchers from the health professions, including doctors, psychologists, and allied health professionals, as well as statisticians, who are involved in the design, execution, analysis and reporting of cluster randomised trials. It is specifically written to address the issues arising from allocating groups of individuals, or clusters, to different interventions, and is primarily concerned with those aspects of cluster randomised trials which differ from randomised trials of individual subjects. Several trials are used as examples throughout the book. These are listed at the front of the book.

1.1 Introduction to Randomised Trials

A formal definition of a trial is given in Box 1.1. The ‘gold standard’ for trials is the randomised controlled trial (RCT), originally developed in order to test the efficacy of new drugs. In the earliest example of such a trial (Medical Research Council, 1948), patients were randomly allocated to treatments, each participant having an equal chance of being given the active drug or placebo. As a result any patient characteristics that might have affected the outcome of the treatment would have been randomly distributed between the intervention and control arms, and the observed difference in outcome between the arms could be attributed to the active drug.

Box 1.1 Definition of a trial

Any research project that prospectively assigns human subjects to intervention and comparison groups to study the cause-and-effect relationship between a medical intervention and a health outcome. By ‘medical intervention’ we mean any inter­vention used to modify a health outcome. This definition includes drugs, surgical procedures, devices, behavioural treatments, process-of-care changes, and the like.

Source: International Committee of Medical Journal Editors, 2009.

Over the years the RCT design has been extended to many other situations: more than two different treatments; crossover trials; non-drug interventions such as surgery, physiotherapy or health education; and in health services research to assess the effectiveness of different models of care.

1.2 Explanatory or Pragmatic Trials

Randomised trials may be used to test causal research hypotheses. Various epidemiological studies have shown that high salt intake is associated with high blood pressure. In order to test whether this relationship was causal, the DASH trial (Moore et al., 2001) recruited a carefully selected group of patients with moderately raised blood pressure and randomised them to take a low salt diet or usual American diet. All the subjects’ food was provided by the trial team. Trials such as this, which seek to understand a biological process, are described as explanatory. Explanatory trials may also test the efficacy of treatments under ideal conditions (Roland and Torgerson, 1998). Cluster randomised trials rarely fall into this category.

Pragmatic trials, on the other hand, are designed to help choose between care options applied in routine clinical practice. Providing a low salt diet for people is not a practical option, except perhaps in hospitals and care homes, and a more realistic approach is to reduce dietary salt using health education for the whole community. The Kumasi trial (Table 1.1) took a whole community approach to health promotion: advice on how to reduce dietary salt was dispensed not only to the individuals participating in the trial but also to their families and neighbours, with whom they might share meals. The intervention was therefore not a ‘low salt diet’ but ‘community education to reduce dietary salt’. Many cluster randomised trials are pragmatic trials and share common features with other individually randomised pragmatic trials (Zwarenstein et al., 2008; Eldridge, 2010).

Table 1.1 Kumasi trial: health education to prevent stroke.

Source: Cappuccio et al. (2006).

Aim: To see if a health education programme to reduce salt intake among rural and semi-rural communities in the Ashanti region of Ghana leads to a reduction in blood pressure

Location and type of cluster: Ghana, villages of 500–2000 inhabitants

Number of clusters randomised: 12

Number of villagers randomised: 1013

Interventions: (i) Control: health education not including salt reduction (ii) Intervention: health education including salt reduction messages

Primary outcome: Reduction in systolic blood pressure after six months

1.3 How Does a Cluster Randomised Trial Differ from Other Trials?

A cluster randomised trial is one in which groups or clusters of individuals rather than individuals themselves are randomised to intervention arm. These clusters are often social units. They can range in size from small units such as households, to much larger units such as towns or regions. Often they comprise individuals connected to particular institutions, for example patients attending particular clinics or general practices, or children in particular schools.

While whole clusters form the units of randomisation (or experimental units) in cluster randomised trials, the members of these clusters form the units of observation. These may be all the members of the cluster or a sample from each cluster. It is this distinction between units of randomisation and units of observation which distinguishes cluster randomised trials from the more usual types of randomised trial, with statistical and practical consequences. In this section we briefly describe the consequences of cluster randomisation, covering recruitment, randomisation, consent, analysis, sample size and interventions. All of these issues are dealt with more fully in later chapters.

1.3.1 Recruitment, Randomisation and Consent

In these key areas, cluster randomised trials exhibit unique features not present in individually randomised trials. Consent to participate may be required from clusters, individuals or both. Even when consent is not required from participants, the methods used to select individuals on whom data will be collected need to be carefully considered in order to avoid bias. This will be discussed in more detail in Chapter 2, but here we describe a few examples to illustrate the wide variability of recruitment, randomisation and consent procedures seen in cluster randomised trials.

A simple trial of radiological guidelines to reduce unnecessary referrals for x-ray by general practitioners is described in Table 1.2. Neither practices nor individuals were asked to consent to participation. Practices regularly referring to one hospital radiology department were identified from the department’s records and randomly assigned to an intervention arm or control arm. Individual general practitioners in intervention practices were sent copies of the guidelines through the post, while those in the control arm were sent nothing. Outcomes were assessed through audit of radiology request forms for individual patients held within the radiology department. Identification of the individual patients, who were the units of observation, was carried out after randomisation, but blind to whether or not their practice was in the intervention arm.

Table 1.2 Guidelines to reduce inappropriate referral for x-ray.

Source: Oakeshott, Kerry and Williams (1994).

Aim: To determine whether postal distribution of radiological guidelines for x-ray referral reduces the number of x-ray referrals from primary care and inappropriate referral for x-ray

Location and type of cluster: UK General practices

Number of clusters analysed: 64

Number of individuals analysed: 2578 (different patients were included at baseline and follow up)

Interventions: (i) Control: no intervention (ii) Intervention: laminat...

Table of contents

• Cover
• Statistics in Practice
• Title page
• Copyright page
• Preface
• Notation
• Table of cases: Trials used as examples in more than one chapter in the book
• 1 Introduction
• 2 Recruitment and ethics
• 3 Designing interventions
• 4 Pilot and feasibility studies
• 5 Design
• 6 Analysis
• 7 Sample size calculations
• 8 The intra-cluster correlation coefficient
• 9 Other topics
• 10 Trial reporting
• Index