Setting up the intervention procedures

This section contains the following:

Introduction
Things to consider
Illustrative example 1
Additional resources

Introduction

Although the trial interventions are defined in the protocol it is important that all sites work through how they are going to deliver this in practice (for example, does a local pharmacy need to be involved and what authorizations do they require?).

All trial sites need to understand how each intervention is to be delivered, including the "control" intervention. This is particularly important when the trail is evaluating a complex intervention (such as the provision of a new service) or an intervention that has more than one component (a multifaceted) intervention such as a trail of audit and feedback and education to promote clinical practice in line with research evidence.

ideally you want to be able to describe each intervention in enough detail to allow direct replication in future trials.

Things to consider

Document the components of each intervention in detail.
Document how each trail intervention is to be delivered.
Train staff about the intervention(s) or treatment(s) and how it should be delivered.
Pilot the delivery /implementation at local sites.
The trial documentation and instructions may need to be in more then one language.
Address specific issues such as treatment formulations, treatment regimes, dosages, equipment, procedures and techniques (if a drug trial).
Address issues around procurement, supply and storage of drugs.

Illustrative example 1 - Magpie Trial

As soon as a woman was allocated a treatment pack, the pack was opened and the trial treatment inside given as directed. Each treatment pack contained 9 x 10ml ampoules of either 50% magnesium sulphate (5g per ampoule;1g/2ml) or placebo, 1g ampoule of calcium gluconate (10ml) in case of toxicity, and an Eclampsia Rescue Pack. Participating hospitals chose whether to use the intravenous or the intramuscular route for maintenance therapy. All other aspects of care were at the discretion of the attending clinician.

The safe use of magnesium sulphate relies on careful monitoring of tendon reflexes, respiratory rate and urine output. Before the trial treatment is started, the clinician checked:

knee or other tendon reflexes are present
respiratory rate is normal (>16 respirations/minute)
urine output was >100ml over the last 4 hours, or >25ml/hour

If tendon reflexes were slow, respiratory rate was reduced but the woman was well oxygenated, or urine output was <25ml/hour treatment could be started, but with half the stated volume of trial treatment for each dose.

If the INTRAVENOUS route for maintenance therapy was used:

The loading dose was 8ml from ampoule 1, diluted with normal saline as usual, and given IV over 10-15 minutes.
For maintenance therapy 10ml from ampoule 2 was given, diluted with normal saline as usual, and given as an IV infusion equivalent to 2ml trial treatment/hour. Continued for 24 hours using ampoules 3-6. Ampoules 7-9 were extra, used if needed.

If using the INTRAMUSCULAR route for maintenance therapy:

The loading dose was given, 8ml from ampoule 1, diluted with normal saline as usual and given IV over 10-15 minutes. 10ml from ampoule 2 was taken and injected IM into one buttock, then 10ml from ampoule 3 was injected into the other buttock.
For maintenance therapy 10ml IM into alternate buttocks was given every 4 hours, using ampoules 4-8. This was 24 hours‘ treatment, and meant the last dose was given 20 hours after the loading dose. Ampoule 9 was extra, used if needed.

Subsequent care for all women entered into the trial was based on the assumption that they were given magnesium sulphate. (MAGPIE Trial - go to publication)

Additional resources

Intervention checklist

This is a checklist for the description of interventions & intervention delivery developed by Dave Sackett (This checklist has been contributed by Dave Sackett, who prepared it for the 3rd edition of Clinical Epidemiology; A Basic Science for Answering Questions about Health Care, to be published by Lippincott, Williams & Wilkins, 2005.

Drug management checklist

This checklist has been contributed by Barbara Farrell who prepared it for the third version of the Trial Management Guide.

CONSORT statement for Non-pharmacological Treatment (NPT) Interventions

This is built upon the CONSORT checklist and takes into consideration specific issues when assessing NPT, such as difficulties of blinding, the complexity of the intervention and the influence of care providers’ expertise and volume of care of centres on treatment effect (from CONSORT website).