Inclusion and exclusion criteria

This section contains the following:

Introduction
Things to consider when writing a protocol
Illustrative example - Single centre trial example: from BMJ 1999
Illustrative example - Multi centre trial example: WHO calcium supplementation trial
Illustrative example - Cluster trial example: Perinatal care trial
Additional resources

Introduction

Every RCT should address an issue relevant to a population with the condition of interest. Trialists should usually restrict this population by using eligibility criteria and by performing the trial in one or a few centres. Typical selection criteria may relate to age, sex, clinical diagnosis, and co-morbid conditions; exclusion criteria are often used to ensure patient safety. Eligibility criteria should be explicitly defined.

Careful descriptions of the trial participants and the setting in which they were studied are needed so that readers may assess the external validity (generalisability) of the trial results. Because they are applied before randomisation, eligibility criteria do not affect the internal validity of a trial.

Pragmatic RCTs are designed not only to determine whether the intervention works, but also to describe all the consequences of its use, good and bad, under circumstances mimicking clinical practice. To achieve this, pragmatic studies tend to use more lax criteria to include participants with heterogeneous characteristics, similar to those seen by clinicians in their daily practice.

Things to consider when writing a protocol

Specifically state the criteria for centre/participant inclusion or exclusion in the trial.
Inclusion and exclusion criteria should be listed separately.
Criteria should include details of all relevant descriptors necessary for eligible centres/participants to be included in the trial, or criteria that would disqualify otherwise eligible centres/participants.
Such criteria may include: facilities; expertise; patient numbers; or participants’ age, sex, or health status.

Illustrative example - Single centre trial example: from the BMJ 1999

Inclusion criteria

Consecutive patients admitted after a snake bite and require antivenom serum due to systemic envenomation or severe local envenomation.

Exclusion criteria

Patients will be excluded from the study if they are;

pregnant
aged under 12 or over 70 years
said they had received antisera, including antivenom serum, in the past
had known adverse reactions to adrenaline, atopy, wheezing, hypertension, ischaemic heart disease, transient ischaemic attacks, strokes, or unexplained focal neurological signs
had received any treatment other than first aid before admission.
or if electrocardiography on admission shows ischaemic changes or arrhythmias.

(adapted from BMJ 1999; 318: 1041-1043 - go to article (included with permission))

Illustrative example - Multi centre trial example: WHO pre-eclampsia trial

Eligibility criteria
Pregnant women attending antenatal care in the participating centres will be eligible if the following criteria are met:

Gestational age <20 weeks
Nulliparous
Willing and able to give consent. (Informed consent for minors will be obtained following country specific age limits)

Randomization will be conducted during the first ANC visit before 20 weeks of gestation. It was decided to include all nulliparous women regardless of their gynaecological history or early pregnancy complications (such as threatened abortion or hyperemesis gravidarum) to cover a high-risk group most readily identifiable. Although there are other risk factors such as positive family history and pre-eclampsia in a previous pregnancy, the screening process to identify these cases is likely to be cumbersome and will be difficult to implement given the diverse populations included in the trial.

Exclusion criteria
Women will be excluded under the following conditions:

History of urolithiasis or symptoms suggestive of urolithiasis or any renal disease such as haematuria, flank pain, etc.
Parathyroid disease.
Blood pressure ≥ 140mmHg systolic or ≥ 90mmHg diastolic, receiving treatment or had history of hypertension.
Taking diuretics or any digoxin treatment.
Plan to deliver in a health facility outside the study area or at home.
Taking phenytoin or tetracyclines.

(WHO Multicentre Randomized Trial of Calcium Supplementation for the Prevention of Pre-eclampsia - go to protocol)

Illustrative example - Cluster trial example: Perinatal care trial

Inclusion criteria for hospitals
Hospitals will be invited to participate in the study if they fulfil the following criteria:

have an Institutional Review Board (IRB), or existing committee which could serve as such, or have an agreement with an IRB which reviews the research protocols implemented in the hospital;
have at least 500 vaginal deliveries per year;
do not have an explicit policy for selective episiotomy and for active management of third stage of labor; and
consent to participate in the study.

Those preselected hospitals will perform a baseline data collection. According to the results of the analysis of the baseline data collection, hospitals will be excluded if the episiotomy rate is low or the rate of active management is high, according to the following cut-off points:

Episiotomy rate in primiparous women with spontaneous vaginal deliveries below 70 %
Rate of active management of third stage of labor over 15%

Because these hospitals do not have a policy for selective episiotomy or active management, it is expected that none of them will be excluded by this criteria. The sample size of the study was increased to allow for exclusions. (CLAP Trial - go to protocol)

Additional resources

Trial Participants Checklist

This checklist has been contributed by Dave Sackett, who prepared it for the forthcoming 3rd edition of Clinical Epidemiology; A Basic Science for Answering Questions about Health Care, to be published by Lippincott, Williams & Wilkins in 2005.