Furthermore, some of the symptoms  of mild TBI, which account for the majority of these injuries in the military,  are similar to those associated with other conditions, such as PTSD. Published Research on the Use of HBO2 Therapy to Treat TBI and PTSD is Primarily Focused on TBI; Conclusions on Effectiveness for Mild TBI Differ

		Most Published HBO2 Therapy Research Is Focused on the Safety and Effectiveness of Treating TBI with Few Studies on PTSD

Most of the 32 peer-reviewed, published articles that we identified  examined the use of HBO therapy for treating TBI: 29 focused solely on  TBI, 2 focused on both TBI and PTSD, and 1 focused solely on PTSD. The 32 articles we identified included 7 case reports, 10 literature  reviews, and 15 articles on interventional studies or clinical trials. Case reports are collections of reports on the treatment of individual  patients. The remaining 12 articles evaluated the effectiveness of HBO The 8  articles on mild TBI had differing conclusions on the effectiveness of  HBO therapy, while the other 4 articles (two on severe TBI and two  that did not specify severity) reported that this therapy was an  effective treatment for these conditions. Articles about the Effectiveness of HBO2 Therapy for Treating Mild TBI Report Different Conclusions

The eight articles on interventional studies or clinical trials that were  focused on treating mild TBI had different conclusions—six articles  concluded that it was not effective and two concluded that it was. The six  articles that concluded HBO Each of the three  studies was affiliated with a branch of military service—Army, Navy, or Air  Force. The remaining two articles were based on two studies conducted  by researchers in Israel and the United States. All of the DOD-funded studies were randomized, double- blinded, and included a sham control group in which participants received  a procedure that is similar to the HBO For a  sham control group in HBO therapy studies, some atmospheric pressure  within the hyperbaric chamber is required for participants to perceive they  are receiving treatment. However, there is no standard sham control  group design for HBO therapy was not effective in  treating mild TBI and related symptoms because participants in the sham  control and treatment groups had similar outcomes. Although both groups  of participants showed improvement, the authors concluded that the  improvement was likely attributable to other factors, such as a placebo  effect, and not to HBO DOD officials and researchers involved  with the studies told us that they believe some improvements were due to  factors, such as being away from home and everyday stress. therapy from this study. In a published editorial, the researchers who conducted the DOD-funded  study that used a sham control group with hyperbaric treatments at 1.2  ATA responded to these concerns by reporting that they recognize that  the sham treatment may have caused physiologic effects from slight  increases in oxygen, nitrogen, and direct pressure, as well as a variety of  other effects. Nonetheless, DOD officials told us that there have been no studies  completed on the long-term effects of the treatment, and such studies  would help confirm whether the sham control groups’ improvements  should be attributed to placebo effects or other factors. DOD and VA researchers and other subject matter experts told us  that these studies were not designed with the same methodological rigor  as the DOD-funded studies on mild TBI because they were not blinded,  randomized clinical trials, and they did not use sham control groups— qualities that help ensure the validity of a study’s findings. The group of  researchers in Israel noted in their article that they did not use a sham  control group because it was difficult to design a treatment for the control  group that would not be considered therapeutic. The researchers for the  other study that was conducted in the United States noted in their article  that a sham control group was not used because this was preliminary  work, and further work would be needed to confirm the study’s findings. therapy to treat stroke. severities of TBI. Appendix I: Literature Review Methodology and Bibliography

To identify and describe published research on the use of hyperbaric  oxygen (HBO) therapy in the treatment of traumatic brain injury (TBI) or  post-traumatic stress disorder (PTSD), we conducted a literature search  for relevant articles published during the most recent 10-year period, from  January 1, 2005 through April 6, 2015. The assignments are determined  by the study protocol. Eight of these articles noted that further research in the area was needed  to determine if this treatment was effective. The remaining 3 articles are related to the  safety of this treatment (see table 10). Appendix VI: Comments from the Department of Defense

Appendix VII: Comments from the Department of Veterans Affairs

Appendix VIII: GAO Contact and Staff Acknowledgments

Debra A. Draper, Director, (202) 512-7114 or draperd@gao.gov.
Why GAO Did This Study

TBI and PTSD are signature wounds for servicemembers returning from the conflicts in Iraq and Afghanistan. Within the military, the majority of TBI cases have been classified as mild. Studies have found that one-third or more of servicemembers with mild TBI also have PTSD. As an alternative to traditional treatments, some researchers have studied the use of HBO2 therapy, which delivers higher levels of oxygen to the body inside of pressurized hyperbaric chambers to promote healing. The Joint Explanatory Statement accompanying the Consolidated and Further Continuing Appropriations Act, 2015, included a provision for GAO to review the use of HBO2 therapy to treat TBI and PTSD.
This report identifies and describes published research on the use of HBO2 therapy for these conditions. GAO conducted a literature review for relevant articles published in peer-reviewed journals during the most recent 10-year period, from January 1, 2005 through April 6, 2015. GAO interviewed DOD, VA, and researchers affiliated with published articles, as well as other stakeholders, including officials with the Undersea and Hyperbaric Medical Society. GAO also interviewed officials from the Food and Drug Administration about the process to approve HBO2 therapy for the treatment of TBI and PTSD.
GAO provided a draft of this report to DOD, VA, and the Department of Health and Human Services. Each of the departments provided technical comments, which GAO incorporated, as appropriate.

What GAO Found

GAO identified 32 peer-reviewed, published articles on research about the use of hyperbaric oxygen (HBO2) therapy to treat traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD), most of which were focused solely on TBI (29 articles). The 32 articles consisted of 7 case reports (reports on the treatment of individuals), 10 literature reviews (reviews of studies), and 15 articles on interventional studies or clinical trials, which provide the strongest clinical evidence about a treatment. Three of the 15 articles on interventional studies or clinical trials focused on the safety of HBO2 therapy for treating TBI and concluded that it is safe. The other 12 articles described the effectiveness of HBO2 therapy in treating TBI. Four of these articles (two on severe TBI and two that did not specify severity) reported that HBO2 therapy was effective. The remaining eight articles focused on mild TBI—six concluded that it was not effective and two concluded that it was.
The six articles that concluded HBO2 therapy was not effective in treating mild TBI were based on three studies funded by the Department of Defense (DOD) with collaboration from the Department of Veterans Affairs (VA) and others. Each of the DOD-funded studies 1) was randomized—participants were randomly assigned to clinical trial groups, 2) was double-blinded—neither researchers nor participants knew who was assigned to which group, and 3) included a sham control group—participants received a procedure that was similar to HBO2 therapy but lacked certain components of the intervention. However, there is no standard design for sham control groups in HBO2 therapy, and in each of the DOD-funded studies the approach varied. The authors of the six articles based on these studies concluded that HBO2 therapy was not effective in treating mild TBI because participants in the sham control and treatment groups had similar outcomes. Although both groups showed improvement, the researchers concluded that this was likely due to other factors, such as a placebo effect. Researchers not affiliated with the DOD-funded studies have raised concerns about whether the sham control groups received a placebo or a therapeutic treatment. In a published editorial, researchers affiliated with one of the DOD-funded studies acknowledged the challenges associated with designing a sham control group and stated that additional research would be needed to determine whether these participants actually received a therapeutic benefit. DOD officials told us that studying the long-term effects of the treatment also would help confirm whether the sham control groups' improvements should be attributed to a placebo effect.
The two articles that concluded that HBO2 therapy was effective in treating mild TBI were based on studies that were designed differently than the DOD-funded studies. DOD and VA researchers told GAO that the studies related to these articles did not have the same methodological rigor as the DOD-funded studies because they did not have design features such as sham control groups, which help ensure the validity of a study's findings. The researchers for one of these two studies noted in their article that they did not use a sham control group because it was difficult to ensure that participants would receive a non-therapeutic treatment. Researchers for the other study noted in their article that a sham control group was not used because this was preliminary work, and further work would be needed to confirm the findings.