Minutes of 3rd Working Group B Meeting
Amsterdam, The Netherlands, 10 December 1999
Participants :
ROQUE Armando Filipe
VAN DER KLEIJ A.J. (Coordinator)
 Accepted by the Management Committee
1. Objective.
2. Study population.
3. Sample size assumptions and estimates.
4. Enrolment of participants.
5. Randomisation.
6. Intervention.
7. Blinding.
8. Evaluation criteria.
9. Assessment of the compliance to the planned treatment.
10. Requirement for Hyperbaric medical centres participating in studies.
11. Publication(s)

The first European Consensus Conference on Hyperbaric Medicine (Lille, France, 1994) has concluded that research in Hyperbaric Medicine has to be directed towards four main fields:
Determining the precise physiopathological basis of Hyperbaric Oxygen therapy (HBO).
Validating methods allowing assessment of HBO effects in patients.
Evaluation of clinical efficacy of HBO.
Evaluation of the quality and pertinence of including HBO in the general care of the patient.
In experimental and animal studies no specific problem has been encountered in applying currently existing guidelines for research in the hyperbaric field.

In clinical research investigators have faced various problems and pitfalls. One of the main subjects of clinical research in hyperbaric medicine is the evaluation of the efficacy of HBO in the treatment of specific diseases. This can be done either for currently accepted indications or for experimental situations.

To consider an indication as experimental for HBO use, there must be a rational hypothesis suggesting a positive effect of HBO in that situation, a reliable system for validating results, and the study must be prospective following the currently accepted clinical research guidelines. However certain specific points have to be emphasised.

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1 Objective.
The objective of the study must include a precise description of the problem and its clinical relevance. It must focus on one question, which will help to define the major endpoint. Other related questions must only be regarded as secondary endpoints.
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2 Study population.
Inclusion and exclusion criteria must be set in order to assume that the selected population is first appropriate to the problem and second homogeneous in terms of severity of the disease or abnormality. Where previous medical history may present a problem the inclusion procedure may be followed in three steps: pre-inclusion, period of standardised care and definitive inclusion.
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3 Sample size assumptions and estimates.
Studies on clinical efficacy can only be done if the incidence of the disease or abnormality is sufficiently high to assure recruitment of the sample size in a time period compatible with the absence of significant changes in the other medical management of the patient.
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4 Enrolment of participants.
Baseline examination has to be well defined particularly with respect to known risk factors. All parameters, which will be used to check homogeneity between groups, must be listed and recorded at baseline.

It must include assessment of all variables used to evaluate the major and secondary endpoints.

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5 Randomisation.
Randomisation must be properly described and may include stratification strategy in order to produce comparable study groups.
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6 Intervention.
The therapeutic schedule must be precisely defined and the intervention group must only have HBO in addition to the therapeutic schedule. No additional treatment must be given to the groups of patients.

It is necessary to define precisely the mode of oxygen delivery.

In case of multiple oxygen delivery systems an assessment of the amount of oxygen delivered to each patient is mandatory.

In case of multiple oxygen delivery systems, statistical analysis must demonstrate homogeneity within the HBO group regarding evaluation criteria.

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7 Blinding.
A double blinding design is often sought in clinical efficacy studies in order to avoid potential problems of bias during data collection and assessment. In HBO studies, the double-blinded design has raised several problems.
First, true compression with hypoxic gas mixture breathing exposes patients of the control group to risk of baro-trauma or even decompression disorders. So it does not respect the principle not to expose the patient of the control group to an undue risk.

Second, sham compression does not guarantee the fact that the patient is blinded due to differences in physical sensation.

Due to this problem, a single-blind approach, or an open study including measures to reduce most potential bias, may be accepted.
Efforts have to be made in order to keep the observer in charge of the evaluation process unaware of the treatment modality.

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8 Evaluation criteria.
Evaluation criteria must include only one endpoint. Others must be considered as secondary endpoints. Frequently in hyperbaric medicine, criteria for evaluation are either non-existent or not internationally recognised. However, if the investigator uses his own table of criteria, he has also to include a conventional table of criteria in order to allow analysis for comparison.
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9 Assessment of the compliance to the planned treatment.
Compliance with the allocated treatment arm must be controlled in every group. In HBO group special attention must be given to the level of oxygen pressure reached during the session. In this respect, transcutaneous oximetry or other techniques of oxygen assessment are useful.
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10 Requirement for hyperbaric medical centres participating in studies.
A hyperbaric medical centre must be physically or functionally linked to a hospital facility or medical institution and must follow the guidelines of the European Committee for Hyperbaric Medicine (ECHM) regarding personnel, safety and procedures.

For studies associated with acute conditions an intensive care facility must be immediately accessible and the intensive care management of the patient must be maintained during the treatment. Studies associated with chronic conditions can be done in hyperbaric medical centres without immediate access to intensive care, providing that the staffing can deal with the additional work.

In case the study involves a multidisciplinary approach the hyperbaric medical centre must be able to provide the proper care and staff needed for that specific situation.

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11 Publications.
Results derived from the COST ACTION research should be published in peer-reviewed, widely recognised, medical journals.
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