Practice-based Research Network Studies and Institutional Review Boards: Two New Issues

Expiring Consent Forms

At the initial review, 13 of the 19 IRBs required us to use consent forms that included a site-specific approval stamp. These 13 IRBs covered approval for 25 practices and the AAFP investigators. In most of the cases the stamp included the date of approval and the name of the IRB. The other sites did not require any specific stamps for the consent forms.

At the time of the first annual review we were told that those 25 sites with stamped and dated consent forms would need to have all consent forms replaced each year with newly stamped and dated consent forms and that all expired unused consent forms had to be collected. Women could only be enrolled on a form for which the enrollment date was included between the approval and expiration date. At the second annual IRB review, 5 additional sites added an approval and expiration date so that 30 of the 31 practice sites required new consent forms after the second year.

This requirement had several implications. First, new English and Spanish consent forms had to be reprinted each year and sent to each site before the expiration date on the previous year's consent forms. All unused consent forms had to be returned to the central site so that we could confirm their destruction. Some IRBs were prompt in sending us the stamped and dated consent forms immediately after the yearly approval, but none sent them more than 1 week before the date on the new consent forms. Other sites did not mail the newly stamped and dated copies to us until after expiration of the old consent forms. Urgent requests to the IRB secretaries were addressed with quick responses (delay of only a few days) by several of the IRBs. However, at 4 sites the delays were 2 weeks, 5 weeks, 8 weeks, and 13 weeks, respectively, meaning that study enrollment had to stop for prolonged periods while we waited for new consent forms. This type of disruption in enrollment is particularly damaging when the study is designed to integrate a practice change into PBRN practices.

To account for the delays encountered at the first annual review related to slow return of the new dated and stamped forms from local IRBs, the second annual reviews were submitted 2 to 3 months before the expiration date on the consent form. This resulted in timely approval of the study but continued slow receipt of the stamped consent forms, with 2 sites having no properly dated consent forms for periods of 1 to 9 weeks. In addition, the second 12-month approval cycle was effective as of the new approval date, which was generally several months before the 2-year expiration date. The implication was that the approval period was not 12 months from the end of the previous year approval but now only 9 to 10 months. During the course of a 5-year study this can result in an extra review cycle, which is time consuming and expensive.

At the time of the study and budget development, we were unaware of the need to print and mail new English and Spanish consent forms to each site each year. We had not had such a requirement for previous PBRN studies. The importance of not interrupting or further delaying patient enrollment led us to use overnight express delivery mail to send the new materials to 29 of the sites (Table 1). The new materials were not only 50 to 100 new consent forms but rather 50 to 100 new full enrollment packets. To facilitate the linking of all study data, Translating Research Into Practice for Postpartum Depression consent forms and study packets include bar code stickers that link the consent forms to the study surveys. This assures that we can link data across survey and consent forms even if the woman's name is not legible on any of the forms. Although this was critical for good data management, it meant that we needed to send each site not only new consent forms with appropriate identifying bar codes but also new survey packets with corresponding bar code numbers. If this study were an academic center-based study in which each site had a paid study coordinator, this might not be necessary because the study coordinator could replace the old consent forms in existing packets. However, for PBRN studies, which work to integrate research into practice, sites do not have the personnel to do this tedious paper work. The need to replace the consent forms, often in a short period of time, required significant central site staff time. By the time we explained the process to each site, copied and collated new consent forms and enrollment survey packets specifically for each site in English and Spanish, mailed them, and followed up on the change of consent form, the central staff spent approximately 6 hours per site per year, or approximately 180 hours per year or 360 hours for all 3 years of patient enrollment.

For the practices that seldom participate in research studies, the need to change consent forms was confusing. The practices were often slow in responding to our request to change forms because they knew the consent form had not changed and did not see any logic of replacing “perfectly good forms.” Changing the color of the consent form from one year to the next might have simplified this activity but several IRBs and practices required that consent forms be printed on white paper. The practices needed white paper to improve scanning quality for placement in an electronic medical record or for filing in paper medical records, which required all visit-related information to be on white paper. To simplify the process within the practices, we attached a colored cover page using a different color for each yearly update of the consent form and survey packets. This page was attached to remind the person providing consent to use the correct forms (for example, red cover sheet for 2006, yellow for 2007, and blue for 2008).

The date on the consent form lead to another area of confusion for some of the IRBs. Three IRB chairs asked that a woman sign a second consent form if her participation extended beyond the date stamped on the consent form. Larger IRBs were clear that the consent was valid for the life of the study but at least these 3 smaller IRBs did not understand the meaning and implication of a dated stamp. We were able to work with those IRBs to eventually achieve agreement that any signed consent was valid for the duration of the study as described within that consent form. The fact that some IRBs did not understand the intent of a time-limited stamp on a consent form suggests that they also did not understand the stamp's possible role in protecting human subjects or perhaps even the need for the stamped date.

When contacted, most IRB secretaries and chairs did not understand our concerns regarding the yearly date stamp. University IRBs’ primary experience with “community” patients was bringing patients from community primary care practices into the university setting or sending full-time research personnel into a community practice to do a study. In either situation, the switching of consent forms would be done by full-time research staff, not the practice staff. In addition, it would not be necessary to return old forms and deliver new forms by mail. Our explanation of how we were conducting our study was considered an unusual case and not worthy of modifying IRB practices. When we asked how the processes improved human subject protection, IRB staff expressed concerns about missing consent modifications and desired assurance that the most recent consent form was being used. Although discussions were polite, no IRB was willing to consider alternative strategies.

Repeating Human Subjects Training

The second issue affecting our PBRN study was the requirement by 8 IRBs, including the one that covered the 13 unaffiliated practices, for all key study personnel to repeat human subjects training. The time for retraining was every 12 months for 2 of the IRBs and every 24 months for the other 6 IRBs. Each IRB also specified which human subjects training materials had to be used; the online CITI training program was the most commonly required. Other sties required programs developed by their institution or one of the medical schools within their state. Retraining was to be done by key personnel, but the definition of “key personnel” also varied between IRBs. The lead study physician and study coordinator were always considered “key personnel,” but other personnel sometimes included all staff members who provided the informed consent or all personnel who implemented the study intervention, which basically included the entire practice staff.

The requirement led to human subjects retraining for a total of 92 people. The burden of this retraining fell on the practices, requiring an average of 90 minutes for each person doing the retraining. In a few cases the CITI program required as much as 4 hours to complete. We estimate that retraining to date has required approximately 200 hours of unreimbursed physician and nursing staff time. For some of the sites a second episode of retraining will be required, adding further unreimbursed costs.

For all IRBs, the required retraining materials were exactly the same as the initial training materials and, in several instances, the test questions at the end of training had not changed from the previous post-training test. The requirement of repeated human subjects training resulted in one site being told they would have to stop enrollment while a staff member who had been on sick leave completed her human subjects retraining.