Randomized Controlled Trials

Introduction

The criticism has been made of hyperbaric medicine that treatment is based on little or no good clinical evidence. Recently improved awareness among medical practitioners to the importance of evidence has highlighted this perception. In fact, many clinical randomized studies investigating the application of hyperbaric oxygen have been reported, although of variable quality.(1-150) It is the purpose of this section to describe the place of RCTs within the practice of Evidence-based Medicine (EBM), summarize the methods by which such trials were located, discuss the appraisal and performance of RCTs with specific reference to hyperbaric medicine, and promote further methodologically sound trials in the field. We will also discuss the generation of meta-analyses based on the individual trials with particular reference to the work of the Cochrane Collaboration.

It is generally accepted that results from well-designed RCTs are the gold-standard for directing clinical decision making.(151-163) The RCT is the most appropriate trial methodology for the investigation of causal relationships between therapy and clinical effects because of a low potential for systematic bias. A randomized methodology, properly concealed and blinded, eliminates systematic bias by removing all factors other than the vagaries of chance in determining to which arm of a study any individual subject will be allocated. No investigator or patient characteristic (e.g. prior belief in the effectiveness of HBO2) can influence allocation between the therapeutic options under consideration. Avoiding the misinterpretation of random events as clinically meaningful is the realm of statistical analysis and appropriate empowerment of well-designed trials. 

Discussions of the ethics of conducting RCTs are available.(151,164-167) Often it is difficult or impossible in life-threatening circumstances to obtain fully informed consent. The ethics of entering such patients in trials is complex and international standards may vary.

Many authorities have listed hierarchies of evidence by trial methodology. While there are minor differences in many of these tables, they all reflect a progression from single case reports or expert opinion (high possibility of bias) to appropriately powered RCTs (low possibility of bias). Table 1, modified from the Oxford Centre for Evidence-based Medicine web site, is an example of such a hierarchy.(168) 

Evidence-Based Medicine

Evidence-based medicine (EBM) as a process by which to practice has only been possible since the development of electronic libraries and search engines. For the first time, rapid access to the vast medical literature published each year is possible, and EBM tools are designed to take advantage of this opportunity. EBM has been defined as "the conscientious, explicit, and judicious use of the current best evidence in making decisions about the care of individual patients.”(169) Despite recent enthusiasm expressed for the concept, many health care professionals have been critical. Some practitioners feel the reference to evidence erodes clinical freedom and is designed by bean counters to control medical expenditure. There are fears that EBM is 'cookbook' medicine- requiring all individuals to receive the same diagnostic and therapeutic measures, regardless of individual needs. This is an unfortunate misconception. While health care providers often attempt to misuse the term ‘EBM' to control expenditure, EBM is actually designed for the use of practitioners. It requires the synthesis of best evidence and clinical expertise/experience in order to arrive at the best diagnostic and therapeutic approaches for each individual under treatment. 

In certain clinical situations, RCTs may be impractical and/or unnecessary for the rational institution of treatment. When dealing with rare conditions, or those with a universally poor outcome, a carefully constructed register of cases or even a retrospective case series may produce evidence powerful enough to drive practice (an ‘all or none' result). The practice of EBM does not involve the slavish regard of RCT evidence only, but the critical appraisal of the best evidence available and the application of the most effective therapy available for the individual patient. The paucity of randomized evidence supporting the application of HBO2 for many indications discussed elsewhere in this report should be interpreted carefully in this regard.

Table 1. An evidence hierarchy for therapeutic interventions

(Adapted from the Oxford Centre for Evidence-based Medicine)

Level

Evidence source

1a

Systematic review of RCTs where the individual RCTs yield homogeneous results

1b

Individual RCT (with appropriate power)

2a

Systematic review of cohort studies where the individual studies yield homogeneous results

2b

Individual cohort study (including low quality RCT; e.g., <80% follow-up)

3a

Systematic review of case-control studies where the individual studies yield homogeneous results

3b

Individual case-control study

4

Case-series (and poor quality cohort and case-control studies)

5

Single case report, expert opinion without explicit critical appraisal, or based on physiology, bench research or "first principles"

Produced by Bob Phillips, Chris Ball, Dave Sackett, Doug Badenoch, Sharon Straus, Brian Haynes, Martin Dawes since November 1998. (Modified by author for this report).

|The practice of EBM is not achieved without effort. Physicians need training to ask appropriate questions, execute efficient searching techniques, develop skills at critical appraisal of the evidence recovered, grasp some basic clinical statistical methods, and relate findings to individual patients. An excellent review of EBM was published in the Journal of the American Medical Society in 1992;(170) another major resource is the pocket guide to teaching and practice of EBM by Sackett and others.(171)

More Information and References can be found in the 13th Edition of the Hyperbaric Oxygen Therapy Indications Book. For Sale CLICK HERE to order