Trial site(s) & population(s)

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Settings and locations affect the external validity of a trial.  Health care institutions vary greatly in their organisation, experience, and resources and the baseline risk of the medical condition under investigation.  Climate and other physical factors, economics, geography, and the social and cultural milieu can all affect a trial's external validity.

Authors should report the number and type of settings and care providers involved.  They should describe the settings and locations in which the trial will be carried out, including the country, city, and immediate environment (for example, community, office practice, hospital clinic, or inpatient unit).  In particular, it should be clear whether the trial was carried out in one or several centres.

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Things to consider when writing a protocol

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Illustrative example - Single centre trial example 1: from the BMJ 1998

Nepal is one of the least developed countries in the world, with an infant mortality of 98/1000 live births, maternal mortality of 1500/100 000 live births, 26% adult literacy, and a prevalence of contraceptive use of 23%.  The estimated population of Kathmandu municipality is 500 000, with an annual urban growth rate of 7.4%.   Prasuti Griha is the main government funded maternity hospital in Kathmandu, with 250 beds, 15 000 deliveries annually, and outpatient services for the local urban and surrounding populations.  As there are no formal addresses in Kathmandu, a house to house survey of two communities will be conducted before the study.  Kirtipur is a periurban area 5 km south west of the hospital that contains 3663 households with a total population of 21 368.  It is a settled community of mainly wage labourers and farmers.  Kalimati is an urban area of central Kathmandu situated 2 km from Prasuti Griha and containing 2467 households with a total population of 13 875. This is a mixed community of long term residents and recent migrants. (adapted from BMJ 1998; 316: 805-811 - go to article (included with permission))

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Illustrative example - Single centre trial example 2: from the BMJ 1999

We will assess the efficacy and safety of low dose, subcutaneous adrenaline as prophylaxis against acute adverse reactions to antivenom serum.  The study is a prospective, randomised, double blind, placebo controlled trial conducted in north eastern Sri Lanka.  It will be carried out during the rice paddy harvesting season, when there is a high admission rate for snake bites.  Consecutive patients will be admitted after a snake bite if they require antivenom serum due to systemic envenomation or severe local envenomation and randomised to receive either adrenaline (cases) or identical appearing placebo (controls) as pretreatment. (adapted from BMJ 1999; 318: 1041-1043 - go to article (included with permission))

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Illustrative example - Multi centre trial example 1: WHO Pre-eclampsia trial

‘The trial will be conducted in antenatal clinics in developing countries serving a population of women with low calcium intake. The collaborating centres will be from the following countries that have expressed an interest to participate in the trial: Argentina, Colombia, Egypt, India, Peru, South Africa and Vietnam. These centres, which have experience in conducting trials, have been contacted and feasibility studies have been completed. These centres also have experience in detailed follow-up of large numbers of women. The study population in these centres should have a considerable proportion of women starting antenatal care before 20 weeks of pregnancy, an already existing routine antenatal care system and capacity to monitor all deliveries. Moreover base-line calcium intake from the populations served by these centres (similar to the population to be recruited) will be completed before enrolment starts.’ (WHO Multicentre Randomized Trial of Calcium Supplementation for the Prevention of Pre-eclampsia - go to protocol)

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Illustrative example - Multi centre trial example 2: from the BMJ 1996

The trial will be conducted in three centres in urban Zambia where primary AIDS care is delivered.  The home care service of the University Teaching Hospital in Lusaka deals mainly with patients referred from the clinics and wards of that hospital.  The patients of this service are transported to their homes on discharge from hospital and visited at home regularly.  The second study centre (with a similar service) will be at Ndola Central Hospital in the north, in Zambia's second most populated city.  The third centre will be at the Kara Counselling and Training Trust in central Lusaka--the Kara HIV Counselling and Testing project provides a drop in advice and primary care service.  The trust also runs several other prevention, training, and counselling projects. (adapted from BMJ 1996; 312: 1187-1191)

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Illustrative example - Cluster trial example 1: Perinatal care trial

‘We will recruit hospitals in two countries because recruiting 24 hospitals in Uruguay alone is not feasible. In Argentina, we will recruit hospitals in the province of Buenos Aires and the city of Rosario. In Uruguay, we will recruit hospitals in the Department of Montevideo. Buenos Aires and Rosario are geographically close to the coordinating center in Montevideo. Even though intervention and control hospitals will be in the same cities, they do not share personnel and are independent entities.’ (CLAP Trial - go to protocol)

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Illustrative example - Cluster trial example 2: from the BMJ 2002

We will conduct this community based, prospective, randomised controlled trial in the Matlab field area of the International Center for Diarrhoeal Disease Research, Bangladesh (ICDDR,B): Centre for Health and Population Research in Bangladesh.  Matlab is a rural subdistrict of Bangladesh where diarrhoea related research has been conducted since 1963.  A health and demographic surveillance system established in 1966 now operates in 144 villages with 210 000 people.  This surveillance system gathers vital event information on births, deaths, and migrations on a regular basis through home visits.  In 1998 infant mortality in the Matlab area was 60.6 per 1000 live births, and mortality in children aged 1–4 years was 5.2 per 1000 children.  Diarrhoea accounted for about 12% of infant deaths and about a third of all deaths in children aged 1–4 years.

Since the inception of research in the Matlab area patients with severe diarrhoea have been cared for in a treatment centre at Matlab township, and patients with severe acute lower respiratory infection have also been treated there since 1980.  Oral rehydration treatment and referral for patients with diarrhoea are provided in the villages by community health workers and by Bari mothers—community volunteers who distribute oral rehydration solution packets and provide advice to patients with diarrhoea.  The community health workers also provide treatment and referral services for acute lower respiratory infection.  On average, there is one community health worker for every 2000 people and one Bari mother for every 50 people. 

The study will include 30 service areas (clusters) of community health workers around Matlab treatment centre, each with about 200 children aged 3–47months. (adapted from BMJ 2002; 325: 1059 - go to article (included with permission))

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Additional resources

Trial Protocol Tool resource icon Population text from the 3rd edition of Clinical Epidemiology

This document 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.

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Trial Protocol Tool resource icon A collection of useful documents

A collection of general documents and recources.

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This page was last updated 24th October 2004.