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The rationale for the trial should describe reasons why the trial question is important.  The intention of the trial may be explanatory (for example to assess the possible influence of a drug on renal function) or pragmatic (for example, to guide practice by comparing the clinical effects of two alternative treatments for renal failure and decide which one has the best outcomes and least harm).  The rationale should include the perceived benefits of any intervention which is to be evaluated.  It should outline how the intervention under investigation might work, especially if there is little or no previous experience of the intervention.

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Things to consider when writing a protocol

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Illustrative examples - Perinatal care trial

Very few trials of a similar nature have been performed in developing countries, and the results of the few that have been performed are inconclusive.  Two trials utilizing educational outreach visits were conducted in Indonesia. Santoso et al. (1996) compared two interventions (outreach visits or a formal seminar) to a nonintervention control to improve drug use in the management of acute diarrhea in children.  They reported that outreach visits resulted in a significant 24% relative reduction in antimicrobial use compared with the control group.  There was a significant 40% relative reduction in the use of antidiarrheals compared to the control group.  The authors also reported that the seminar resulted in significantly greater changes from the baseline period than did the outreach group.  The use of oral rehydration agents was not significantly improved after either intervention (9% reduction). Ross-Degnan and colleagues (Ross-Degnan et al., 1996) reported that outreach visits to pharmacists/owners, coupled with a small group session with counter attendants, significantly increased sales of oral hydration salts by 40% and reduced antidiarrheal sales by 35% for the treatment of diarrhea.

In sum, multiple strategies to change medical behaviors have been used, with various degrees of success.  Few trials have been done in obstetrical settings or in developing countries.

To our knowledge, no randomized controlled trial has been performed to evaluate the effectiveness of an intervention to implement evidence-based birth practices in Latin American countries. (CLAP Trial - go to protocol)

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Illustrative examples - Magpie trial

Why is a trial needed now?
In 1995, magnesium sulphate was shown to be the anticonvulsant of choice for women with eclampsia (see table).  These results had a major impact on both practice and policy throughout the world.  Magnesium sulphate for the treatment of eclampsia is now included in the essential drugs list of the World Health Organisation and is recommended in the practice guideline produced by the Royal College of Obstetricians and Gynaecologists, London.

Data from the Collaborative Eclampsia Trial on maternal deaths and recurrence of convulsions

Chart showing maternity mortality data
*RR = relative risk; CI = confidence interval; * outcome not known for 1 woman

Having switched to magnesium sulphate for women with eclampsia, many clinicians are also reviewing their policies for anticonvulsant prophylaxis.  As discussed above further evidence is required to help them decide whether its use would be beneficial and, if so, for whom.  Nevertheless many clinicians have begun using magnesium sulphate for women with preeclampsia, and others are considering starting to use it.  There is currently a window of opportunity for properly evaluating this use of magnesium sulphate.  Results of the Magpie Trial will provide a reliable basis for decision-making about the care of women with preeclampsia. (MAGPIE Trial - go to protocol)

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Illustrative examples - ISAT trial

Endovascular techniques for the treatment of intracranial aneurysms have been evolving over the past 10 to 15 years.  The Guglielmi Detachable Coil device (GDC) has been in use in Europe since 1992 and in North America since 1991 and is a major technical advance.  Recent data from the USA multicentre assessment of the GDC device prior to FDA approval showed a complication rate similar or even better than conventional neurosurgery in a selected high surgical risk group.  The GDC device has been used in approximately 4,000 patients world-wide.  It has significantly improved endovascular treatment by providing a technically safer and more reliable coiling system.  Early clinical results with this device in the posterior circulation were published in 1995 and a review of the multi-centre North American experience in the first 1,058 patients has been presented by senior investigators of this system.  Data from the clinical co-ordinating centre, and unpublished results from other centres with significant endovascular experience suggest complication rates of aneurysm treatment following aneurysmal subarachnoid haemorrhage (SAH), appear to be in the range of 1.5-5% mortality and 3-5% morbidity.  Observed rebleeding rates are less than 1% of treated patients.  The patient selection in these series have tended to be patients with more difficult surgical aneurysms, larger size, patients in poorer clinical grade and with a high proportion of posterior circulation aneurysms. 

An editorial in Journal of Neurosurgery, reviewed the current situation and whilst recognising potential limitations, advocated the development of protocols for a randomised trial comparing endovascular treatment with neurosurgery. (ISAT Trial - go to protocol)

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Illustrative examples - Cluster trial example

About three-fifths of all perinatal deaths of normally formed singletons are late (beyond 28 weeks) antepartum deaths.  There is no obvious cause for about 70% of these deaths, most are unpredictable, and the extent to which they can be prevented by current antenatal care is limited.  Because these deaths may be preceded by reduction or cessation of fetal movements for a day or more, recognition of such reduction, followed by action to confirm jeopardy and expedite delivery, might prevent such deaths.  Thus, formal fetal movement counting has been proposed as a routine screen in all pregnancies to identify fetuses likely to be compromised, rather than formal counting in high risk cases or leave it to women to note changes in movements informally.  The value of fetal movement counting for predicting fetal death appears to be good.  In a small controlled trial Neldam showed that routine formal counting was associated with a significantly lower rate of antepartum death among normally formed babies weighing more than 1500g than informal noting.  This finding was not predicted before the trial, however, and a non-randomised cohort study of 20,000 women failed to identify any such benefit.

Routine formal fetal counting would involve substantial resources for maternity services and for the women.  In view of uncertainties about effectiveness, we will conduct a large, multicentre, international, randomised controlled trial. (adapted from Lancet 1989;ii:345-9)

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This page was last updated 4th June 2004.