Looking for more than hot air: how experimental design can enhance clinical evidence for hyperbaric oxygen therapy

Abstract

Hyperbaric oxygen therapy is emerging as a potential treatment for critical medical and psychological issues, including mild traumatic brain injury, traumatic brain injury, and post-traumatic stress disorder. Based on the promising results from numerous case studies, randomized clinical trials generated conflicting interpretations despite frequent improvements in patient symptoms. The primary debate concerns whether the therapeutic benefits could be attributed to placebo effects or sham conditions that actually induce a therapeutic state. In part, the contention has been exacerbated by experimental designs which could not properly account for extraneous variables, such as the potential for differing patient expectations to influence the outcome. The current discussion addresses five methodological challenges that complicate any determination of clinical significance due to experimental design. These challenges include: 1) not properly addressing or controlling patient expectations prior to the experimental sessions; 2) the challenge of experimental masking in clinical designs that require pressurized environments; 3) patient subjectivity in the primary dependent variables; 4) potential fluidity in patient symptoms or data, such as regression to the mean; and 5) the potential for nocebo effects to exaggerate treatment benefits by lowering performance expectations during pre-treatment assessments. Each factor provides an influential means by which placebo effects could complicate results and prevent the combined data from reaching a threshold of clinical significance. The discussion concludes with methodological best practices with which future research could minimize placebo effects and produce more conclusive results.