This paper outlines the development of an international, multicenter, prospective registry consortium. A center joins the consortium by signing the consortium agreement. This agreement covers membership, governance, data sharing requirements, use of member data, publications, intellectual property, liability, confidentiality, and insurance. Data are collected using Research Electronic Data Capture (REDCap), a widely available, easily accessible, Health Insurance Portability and Accountability Act (HIPAA)-compliant, web-based data collection system [17]. Each participating center determines its own start date for data collection (ie, reference date) and records baseline data for every patient referred to the treatment center, whether or not treatment is indicated for, or accepted by, the patient after that start date. Patients included in the registry are those patients who have been evaluated for possible treatment of any UHMS-approved condition, or any non-UHMS-approved condition, including those who are part of research studies or trials. The registry gathers data on whether the evaluation determined that treatment was contraindicated, indicated and scheduled, or indicated but declined by the patient.

Each center’s participation is overseen by its own US Institutional Review Board (IRB) or the country-specific equivalent, or a center can opt to rely on the Dartmouth Committee for the Protection of Human Subjects (ie, the Dartmouth IRB). The REDCap-based data collection template is the same at all centers, so all centers collect the same outcome measures. Quarterly, each center performs a deidentified data download from their REDCap database to the coordinating center’s REDCap database at Dartmouth College. These deidentified data from each center are combined into a single REDCap database, which is the multicenter data registry. Optional consent for longer-term follow-up is being pilot tested at one center.

The design approach to the registry is to create a system that can be used at any hyperbaric center. This means the system must be low cost and not require excessive staff effort. Although gathering data from electronic medical record systems is desirable to avoid repeated data entry, this is not practical for this project due to the diversity of medical record systems and the level of effort and funding required to standardize and update outcome measures and procedures among them. To minimize staff effort, data entry needs to be minimal, which means extensive data on comorbid conditions, medications, and medical history cannot be collected. Instead, the registry has to focus on a few key outcome measures whose data any center can collect and enter reliably. For studies using registry data where more information on the individual patients is needed, an interested investigator can obtain IRB or ethics approval to work with more detailed data at the individual centers using procedures outlined in the consortium agreement.

The registry database was initially designed by a consensus of founding members of the HBO₂ research consortium—the Geisel School of Medicine at Dartmouth in Hanover, New Hampshire, and the Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire—and core data are collected for UHMS-approved and some nonapproved conditions. Data are collected using four main data collection instruments (see Table 2). The Demographics instrument collects demographic information as well as information on insurance and distance traveled. The Pre Treatment Information instrument collects information on the condition being treated, treatments prescribed and administered, and subjective and objective measurements of the patient’s status at treatment start. A quality-of-life measure—the EuroQol, 5-dimension, 5-level (EQ-5D-5L)—is also administered at baseline on all patients [18,19] as part of the Pre Treatment Information instrument. The Pre Surgical Information instrument collects subjective and objective measures of the patient’s status prior to a surgical intervention (eg, tooth extraction) if one is performed. The Treatment and Outcomes instrument repeats information collection of the Pre Treatment Information outcome measures, records the actual treatment given, asks about complications, and repeats the quality-of-life questionnaire.

Both indication-specific outcomes and general outcomes are collected, including HBO₂ treatment complications (eg, changes in refraction, seizures, pneumothorax, confinement anxiety, barotrauma, and placement of pressure-equalization tubes in the ear). Wherever possible, common objective outcome measures are used. The registry uses validated questionnaires that have supporting evidence in the literature (eg, the Common Terminology Criteria for Adverse Events [CTCAE] hematuria grading scale for radiation cystitis and the European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire Head and Neck [QLQ-H&N35] for head and neck symptoms) [20,21] as well as some questionnaires that were custom developed for the registry (see Table 2) [22-24]. Factors that might affect the effectiveness of the therapy are also collected (eg, diabetes, smoking, and other nicotine use). Future plans, including long-term follow-up and linkage to cancer registries and vital status data, depend on future funding. Table 3 lists the parameters measured [25,26].

The HBO₂ Registry Consortium includes member institutions fulfilling the requirements as shown in Textbox 1. A steering committee is responsible for the governance of the registry. The Geisel School of Medicine at Dartmouth and the Dartmouth-Hitchcock Medical Center are the founding members of the consortium and each have representatives on the steering committee. The steering committee also includes a representative from each participating center. By a majority vote, with affirmative votes from the founding members, the steering committee has the authority to set the strategic direction for the registry, admit or remove members, set membership fees, establish policies, and relocate the registry. Member-initiated research protocols are approved by a majority vote of the steering committee. The committee also votes on any changes to the REDCap data collection instruments. The steering committee meets annually at the UHMS annual meeting, where changes and modifications to the registry are discussed and voted upon. Template IRB application materials are freely shared between participating centers.

Descriptive analyses will be conducted to describe the baseline characteristics and outcomes of patients with each indication, overall and by center, including the numbers, proportions, and confidence intervals for the following: patients with each indication for treatment; those evaluated who were not treated or who were partially treated and the reasons why; baseline characteristics, including referral information and baseline outcome measures; treatments given; occurrence of each type of side effect; and outcome measures at the end of treatment with change scores and relative change scores, as appropriate. For measures with numerical scores, we will assess absolute and relative changes; for other measures, we will report outcomes in terms of the proportions with symptom resolution, improvement, no change, or deterioration. Factors associated with key outcomes will be explored using multifactorial analyses where sample size is sufficient for models to be stable. All results will be presented and discussed in terms of estimates and 95% confidence intervals to avoid focusing on P values alone.

An HBO₂ treatment outcomes registry is feasible and can provide consistently recorded outcomes from HBO₂ treatments at multiple centers. Initial analyses of some of the outcome data are already showing significant changes after HBO₂ treatment.

A key strength of the registry is its use of REDCap [17], a free, secure, web-based, data collection system used to build and manage online surveys and databases in more than 3964 centers worldwide. The HBO₂ REDCap database has been pilot tested and revised at the coordinating center for 6 years, and core variables have been collected on UHMS-approved indications for HBO₂ treatment, as well as some non-UHMS-approved indications. The database includes 1996 variables, many of which are disease specific and are programmed to appear only for particular indications or situations (ie, during data entry, a staff member will only be entering data on a small subset of the variables available). Data entry takes an average of 15 minutes per case, distributed over several clinical visits. The template for the database can be exported to Excel, emailed to another center, and easily uploaded to create an identical registry that is ready for data entry. REDCap provides the ability to perform a deidentified data export from each participating center. This is sent to a central, pooled REDCap database at the Geisel School of Medicine at Dartmouth. Because of the simplicity of the software and the relatively low burden of data entry, the registry is relatively inexpensive for new centers to install and maintain. Because only deidentified data are pooled, the risk to participants is minimal.

At present, the registry is following individuals who receive HBO₂ treatment, and a registry of similar patients with similar conditions who are not receiving HBO₂ treatment does not exist. Therefore, there is no way to compare outcomes from HBO₂ treatment directly with outcomes from similar patients who did not receive the treatment. As the registry grows, an additional limitation will be funding, which will be needed to maintain a system of data-quality oversight, analysis, longer-term follow-up, and other registry-related activities.

An outcome-focused registry for HBO₂ treatment is needed urgently to provide both patients and providers with the information they need to decide whether and how to use HBO₂ treatment. To be successful, this registry must be practical, easy to use, and easily expandable. The registry described here meets these requirements. The data entry requirements are not excessive and should be within the capabilities of existing staff at any given hyperbaric center. Also, by using REDCap, the registry can be expanded to include detailed information on particular indications and long-term follow-up on selected patients without significantly increasing the basic data entry requirements.