Table 2. IRB process and results from the first five-region, network-wide clinical study in DPBRN.

DPBRN Region	Process and result
Alabama/Mississippi*	First iteration: University of Alabama at Birmingham IRB approves a six-page Informed consent Form and a one-page HIPAA form, which the patient signs. Feedback from Alabama/Mississippi DPBRN practitioners and patients doing Study 2 suggests that the informed consent process for this study is very cumbersome and creates suspicion. DPBRN then submits an application to the University of Alabama at Birmingham IRB for a revised protocol. The HIPAA form is revised to adapt it to the PBRN context, from its earlier default version that was written for the hospital and university research environment. Final iteration: University of Alabama at Birmingham IRB approves a one-page Patient Information Sheet that is given to the patient. Informed consent is obtained verbally with documentation by the practitioner-investigator in the patient's chart and Study 2 log that informed consent was obtained.
Florida/Georgia	First iteration: University of Florida IRB approves a nine-page Informed Consent Form and one-page HIPPA form, which the patient signs. Results from the University of Alabama at Birmingham IRB re-application described above creates openness to further revision. The Florida/Georgia region submits an application for a revised protocol to the University of Florida IRB. Final iteration: University of Florida IRB approves a two-page Informed Consent Form that the patient signs.
Minnesota	First iteration: Following face-to-face discussions with the IRB in advance of the IRB application, HealthPartners Research Foundation IRB approves a waiver of documentation of informed consent because the study involves routine treatment that will be done anyway.
Permanente Dental Associates	First iteration: Kaiser Permanente Northwest IRB approves a four-page Informed Consent Form with modified HIPAA language. The patient signs both forms. Final iteration: Kaiser Permanente Northwest IRB approves a two-page Informed Consent Form with a carbon copy attached so that the patient can be given a copy at the time of signature.
Scandinavia/Denmark	First iteration: The Danish ethics committee for the applicable region of Denmark concludes that research of this type is not under its purview and refers it to the Danish Data Protection Agency. Second iteration: The Data Protection Agency approves the study, but the University of Alabama at Birmingham IRB cannot accept its finding because this agency does not have a Federal-wide Assurance number. Third iteration: The Danish region re-applies to the ethics committee, which makes the same conclusion as before. Fourth iteration: A telephone conference call is held between the Danish ethics committee and the University of Alabama at Birmingham IRB. The Danish ethics committee sends a letter to the University of Alabama at Birmingham IRB confirming its approval of the study as a result of its review for “local context” and that it is willing for the University of Alabama at Birmingham IRB to serve as the IRB of record for Study 2 and other minimal-risk observational studies. Final iteration: DPBRN submits a revised application to the University of Alabama at Birmingham IRB, asking it to serve as the IRB of record for Danish practitioner-investigators. University of Alabama at Birmingham procedures apply with “local context” taken into account.
Scandinavia/Norway	First iteration: The Norwegian ethics committee declined to send a letter to the University of Alabama at Birmingham IRB confirming that it approved of the Study 2 protocol. Second iteration: The Norwegian ethics committee for the applicable region of Norway concludes that research of this type is not under its purview and the Norwegian Data Protection Agency accepts the finding of the Danish Data Protection Agency without any further review. Third iteration: A re-submitted application is reviewed and approved. Fourth iteration: A revised application to use a verbal informed consent process is reviewed and approved.
Scandinavia/Sweden	First iteration: The Swedish ethics committee declined to send a letter to the University of Alabama at Birmingham IRB confirming that it approved of the Study 2 protocol. Second iteration: The Swedish ethics committee for the applicable region of Sweden concludes that research of this type is not under its purview and the Swedish Data Protection Agency accepts the finding of the Danish Data Protection Agency without any further review. Third iteration: A re-submitted application is reviewed and approved. A verbal informed consent process is included in that application.

HIPAA: Health Insurance Portability and Accountability Act