CTSA Profile
Frontiers: Integration of a Research Participant Registry with Medical Clinic Registration and Electronic Health Records Patricia M. Kluding, Ph.D.1, Jo Denton, M.S.N.2, T. Rene Jamison, Ph.D.2, William Brooks, Ph.D.2, Karen Blackwell, M.S.2, John D. Lantos, M.D.3, Lemuel R. Waitman, Ph.D.2, Tamara M. McMahon, M.S.2, Arvinder Choudhary, M.S.4, Marjorie J. Bott, Ph.D.2, Allen Greiner, M.D.2, Susan Klaus, Ph.D.2, Amy O’Brien-Ladner, M.D.2, Lauren S. Aaronson, Ph.D.2, Jeffrey Burns, M.D.2, and Richard Barohn, M.D.2 Introduction
P
articipant recruitment is a significant challenge to the success of clinical research. Without sufficient study participants, investigators cannot meet accrual goals and studies either must be abandoned without reaching recruitment targets or prolonged.1,2 Recruitment of study participants can be facilitated by maintaining registries of people who agree to be contacted for future studies. Registries range from simple databases that include only contact information, to more sophisticated regional and national registries that include individual health information and that can be searched for individuals who meet specific study criteria.3–7 Such registries clearly facilitate recruitment, but they can be costly to develop, advertise, and maintain.3,5,6,8–11 Frontiers: The Heartland Institute for Clinical and Translational Research is an academic home for clinical and translational research, headquartered at the University of Kansas Medical Center (KUMC) and partly funded by a Clinical and Translational Science Award (CTSA) from the National Institutes of Health since 2011. The vision of Frontiers is to improve the health of the region through a novel and transformative translational research enterprise from the bench to bedside to community. In this paper, we report our experience in establishing the Frontiers Research Participant Registry and highlight the unique combination of features that differentiate it from other registries: (1) Registry enrollment is integrated into outpatient clinic registration, as all clinic patients have the opportunity to provide permission to be contacted for studies for which they are eligible; (2) The registry is aligned with the complete electronic health record (EHR) that can be searched to provide the total numbers of clinic patients who meet inclusion/exclusion criteria; (3) Investigators with IRB-approved studies can receive contact information for those patients who meet criteria and who have given permission to be contacted; (4) The registry provides a HIPAA-compliant means for investigators to contact only those potential participants who meet inclusion/exclusion criteria based on their EHR. Together, these features have yielded a highly successful program with a growing database of over 31,000 individuals who have agreed to be contacted for research recruitment. The Frontiers Research Participant Registry
Important operational components of the Frontiers Research Participant Registry are described below. The enrollment process and operation of the registry is illustrated in Figure 1.
Authorization form A single-page participant authorization form was developed by the university’s HIPAA compliance officer (current version is included in the Appendix). This “permission to contact” form provides a brief description of the registry along with privacy assurances. The form is provided to patients during check-in at outpatient clinics in the University of Kansas hospital system. A signature line indicates permission to: (1) use the enrollee’s medical information to identify if they are a potential candidate for a study, and (2) release the enrollee’s contact information to investigators with IRB-approved studies. Enrollment in the registry is documented in the billing system software (IDX GE). A checkbox is used to indicate the patient’s willingness to be contacted. Customized data entry fields indicate the date the form is presented to the patient and whether the patient agrees or declines to sign. Once the form has been presented to a patient, it is not presented again at subsequent visits. The patient receives a copy of the form, which has our contact information if they change their mind and wish to withdraw their permission. There is also a field to document whether the patient subsequently withdraws their permission (i.e., if an individual informs a study recruiter or the Frontiers office that they wish to have their name removed from the registry). The authorization form provides a default option for e-mail communications to be sent through a secured system. Individuals may select two alternatives to this default for e-mail communication: (1) to permit e-mail communication sent through unsecured systems, or (2) to decline all e-mail communications. If those lines are initialed, those preferences are indicated in the corresponding data entry fields. Tracking authorizations through a checkbox in the EHR simplified our regulatory requirements. We obtained clarification from the federal Office for Human Research Protections that because the registry is integrated into the EHR rather than maintained as a separate recruitment database, the project would not be human subjects research. Therefore, IRB approval of our registry and an IRB-approved informed consent process are not required. Data repository An integrated clinical data repository containing EHR, billing, and research data across the KUMC enterprise was developed by the Frontiers Medical Informatics core team. The Healthcare Enterprise Repository for Ontological Narration (HERON)12 is an
1 Department of Physical Therapy and Rehabilitation Science, University of Kansas Medical Center, Kansas City, Kansas, USA; 2University of Kansas Medical Center, Kansas City, Kansas, USA ; 3Children’s Mercy Hospital, Kansas City, Missouri, USA ; 4Baptist Health, Jacksonville, Florida, USA . Correspondence: Patricia M. Kluding ( [email protected])
DOI: 10.1111/cts.12309
WWW.CTSJOURNAL.COM
VOLUME 8 • ISSUE 5
405
Figure 1. Overview of enrollment and operation of the Frontiers Research Participant Registry. HERON is the Healthcare Enterprise Repository for Ontological Narration, an EHR data repository. The copyright of this figure is retained by the authors of the paper.
IRB-approved data repository that uses the i2b2 (Informatics for Integrating Biology and the Bedside) framework.13 The identified EHR and billing records are merged into an i2b2 format and stored on a dedicated server with limited access. Data are then deidentified to remove protected health information and moved to a separate dedicated server that can be browsed directly by clinical researchers. As part of the deidentification process, all dates in the EHR are shifted randomly (1 to 365 days into the past); the shift is different across records but constant within the records of each patient. Investigators within our institution use the i2b2 Query and Analysis Tool to search against the fully deidentified data in HERON. This is useful as a first step to identify the total number of individuals who meet specific study inclusion and exclusion criteria and who have enrolled in the Frontiers Research Participant Registry, and provides investigators with information on the pool of potential participants. Other relevant data sources within HERON include the Social Security Death Index (a valuable exclusion criterion), University HealthSystem consortium hospital quality indicators and statistics, university-held biospecimens, and the hospital 406
VOLUME 8 • ISSUE 5
tumor registry. These queries may be performed preparatory to research during the proposal development or grant submission phases and can be completed prior to receiving IRB approval. This includes visualizing timelines of patients’ longitudinal care records and descriptive statistics (e.g., gender, racial, vital status proportions) of the potential study cohort. Once a study is IRB approved and ready to recruit, the names and contact information of registry participants may be requested as described below. Recruitment registry request committee The Recruitment Registry Request Committee (RRRC) is the gatekeeper for requests for contact information for people who enrolled in the registry and whose EHR indicates potential eligibility for a specific study. Membership of this committee includes representation from Frontiers senior leadership, the hospital and physician practice group, the HIPAA compliance office, established investigators from multiple disciplines, and a community member. Investigators with an IRB-approved study must first search the deidentified data in HERON to determine the number of WWW.CTSJOURNAL.COM
individuals in the registry who meet the specific inclusion/ exclusion criteria for their study, as described previously. This step also allows investigators to “fine-tune” their search to best suit the specific study needs within the context of the available patient census. A request for contact information may then be submitted to the RRRC for review. If approved, a passwordprotected spreadsheet containing contact information is provided to the study team. It is important to emphasize that the spreadsheet contains contact information only of individuals who meet the predetermined criteria. Although information in the EHR is used to identify the potential participants, no specific information about medical history, birthdate, medical record number, or other protected health information is provided to the investigator. Investigators typically contact the registry participants to determine interest in the study and ask screening questions to confirm eligibility. It is at this point that investigators can request specific medical information from the participant either by self-report or through access to the EHR under normal IRB-approved procedures. Investigators are required to report back to the Frontiers RRRC on the number of individuals contacted from the list and the number enrolled in the study. If any individual asks to have their name removed from the registry, the EHR record is modified to indicate that they have withdrawn, and their name is not provided in future searches. Key Developmental Steps
Stakeholder engagement With three contributing organizations representing the university, the hospital, and the physician practice group, the negotiation of a master data sharing agreement was an essential initial step to establish the governance and security of the registry. This legal document was signed by the executive leadership of each contributing organization. Under the conditions of agreement, the university was responsible for creating and maintaining the HERON data repository and supplying the information to investigators (i.e., medical center faculty). The hospital agreed to contribute information from the EHR, and the physician practice group agreed to contribute data from the billing system. An executive committee with representation from each organization was formed to provide oversight, and a subcommittee composed of the leaders from all three parties meets monthly to provide review and set direction for the development of this campus resource. Another important step in the development of the registry was the engagement with a broad representation of institutional stakeholders at all levels to gather feedback and respond to questions or concerns. The Frontiers research participant advocate served as the initial director of the registry program, which served to promote professional integrity and transparent communication to potential research participants. Prior to implementing the registry, the Frontiers leadership team presented extensively to executive leadership of the university, hospital, and physician practice group, to investigator groups, and to clinical departments. One concern about the registry raised by physicians in early discussions was the need for a mechanism for them to be informed if their patients enrolled in a clinical trial. They were concerned that their patients might receive medication or treatment that would interfere with their standard care and present a safety issue. In response to these concerns, investigators are required WWW.CTSJOURNAL.COM
to provide the RRRC with a template letter they will use to inform participants’ health care providers about the study prior to receiving names from the registry. Pilot testing To test the Frontiers Research Participant Registry enrollment and governance processes before wide implementation, a pilot program was started in 2009 at four clinics in the KUMC system representing a diverse sample of clinical disciplines: Neurology, Pulmonary, Diabetes, and the Center for Child Health and Development. The RRRC met monthly during this period to evaluate the process and identify modifications that were needed. Formal reviews and updates to participating clinical department chairs were performed after 1 month, 5 months, and 8 months. After 1 year, the program was expanded to three additional clinics (Clinical Pharmacology, Pediatrics, and Ophthalmology), and after 2 years, the program was expanded to a total of 20 outpatient clinics. At each clinic, members of the Frontiers administrative team met with individual clinic registration personnel to provide training on the form and the process. A short summary in a FAQ format was provided to the front desk staff on procedures and how to answer common questions. Initially, registration clerks reported a burden from presenting the forms at check in, providing a copy of the signed authorization form to each patient, and documenting the signature data in the EHR. To address these barriers, forms were printed on duplicate paper to eliminate copying. The registration clerks simply give the patient one copy and send the other to the Frontiers office by internal mail using a prelabeled envelope. Frontiers staff annotate the EHR using the customized data entry fields to indicate date and permission to contact as described previously. During the first year of the pilot program, several modifications to the enrollment form were made. For example, a “yes” or “no” checkbox for agreement to be contacted for future studies was included in an early version of the form, but this was replaced with the statement: “If you do not want to be contacted about research, do not sign this form.” A Spanish-language version of the form also was developed and implemented. Growth of the registry The Frontiers Research Participant Registry has grown rapidly. Within 5 years of starting the pilot program, more than 31,000 people were enrolled (Figure 2). Approximately 1,000 new enrollment forms are received each month from the clinics. Use of the registry by investigators has grown with the increased number of individuals enrolled in the registry, as illustrated in Table 1. As of January 2015, the RRRC has reviewed and approved requests for contact information from 47 different investigators for 67 distinct study protocols. These investigators represent multiple departments as illustrated in Figure 3. Lessons Learned
The development and implementation of the registry represented a significant investment from the CTSA leadership, especially the Medical Informatics, Regulatory, Community Engagement (Community Partnership for Health) and Ethics cores and the Clinical and Translational Science Unit (CTSU). Once the registry was implemented, it was essential to identify a director within the leadership of these cores who would continue to be responsible for the maintenance and growth of the registry. VOLUME 8 • ISSUE 5
407
Figure 2. Cumulative enrollment for Frontiers Research Participant Registry 2009–2014.
Figure 3. Number of requests received each year from principal investigators (# PIs) representing multiple departments (# depts) for study recruitment using the Frontiers Research Participant Registry 2009–2014.
Year
Number of names provided to study teams*
Number of registry participants contacted†
Number of registry participants enrolled‡
2009
42
15
4
2010
66
12
0
2011
676
179
15
2012
3,745
1,041
146
2013
3,892
781
13
2014
11,988
1,514
39
Totals (to end of 2014)
20,409
3,542
217
*The names provided are people who meet all inclusion/exclusion criteria based on their current EHR and who have agreed to be contacted for research purposes. † Not all names provided are contacted for a variety of reasons—study may close, participants may not respond, or contact information may have changed. ‡ Investigators provide final numbers on number of registry participants enrolled after the study closes, so 2013 and 2014 reports are incomplete as many of those studies are still active.
Table 1. Utilization of the Frontiers Research Participant Registry by investigators.
Resources Financial and personnel resources are required to support and grow the registry, including the director position, medical informatics support, and administrative support. While registry enrollment status is automatically added to the HERON system as part of the monthly processes that add billing records, medical informatics also provides participant information to study teams following RRRC approval in the role as an honest broker, and provides technical or system support. We have found that approximately 0.75 FTE of additional administrative support is needed to maintain the registry. These activities include communication with the clinic registration/front desk personnel, processing the enrollment forms and data entry to indicate registry enrollment, providing administrative support to the RRRC review meetings, responding to investigator questions about the registry, and providing assistance with performing and refining the HERON queries. Contact is made with each clinic at least once each month to reinforce the importance of their efforts for clinical research and to ask if they need additional forms or envelopes. Repeated training is required due to staff turnover or other administrative changes in the enrollment process. While the Frontiers program has supported the registry to date, other sources of support are being explored to ensure 408
VOLUME 8 • ISSUE 5
sustainability of the registry. These include partial support from infrastructure grants, like the current CTSA grant and other Frontiers resources, general institutional support, and use of charge-back mechanisms similar to other core resources at academic health centers. Authorization form and e-mails After the pilot testing, the authorization form did not change significantly for the first 4 years of the program. However, we noted an increasing interest in e-mails as a preferred means of contact for potential research participants. After extensive legal consultation, the revised form now lists e-mail address as one type of contact information investigators would receive, with an opt-out option (see Appendix). We now are able to provide e-mail contact information for new enrollees. However, acquiring this permission from the 31,000 past enrollees who signed the previous form presents a significant logistical challenge that we have not yet solved. An additional challenge with e-mails arises from our current university policy that requires e-mails with protected health information to be sent through a secure system. As this system requires recipients to create a user name and password to access the e-mail content, it is a significant barrier to communication. WWW.CTSJOURNAL.COM
This policy is currently being examined with a view to allowing e-mail sent through a nonsecure system if individuals give their permission. Therefore, this item was included on our revised authorization form. RRRC review The majority of RRRC requests are approved without concern, after verification of IRB approval and refinement of HERON search results. There have been some situations where different study teams requested participants with similar characteristics, and this has been handled with different strategies. In some cases, the second request was delayed until recruitment for the first study was completed to avoid frequent contacts of registry participants with competing study requests. Alternatively, the principal investigators of the competing studies have been asked to find a mutually acceptable compromise particularly in situations with PIs from the same department or who are collaborating colleagues, as the value of continued collaboration and collegial relationships has been noted to provide an incentive for compromise in these situations.14 To date, these types of conflicts have been rare and handled on an individual basis. However, as the registry program grows we anticipate an increased number of potential conflicts. It may be appropriate to institute a priority scoring system that incorporates a rating of scientific merit, assigns higher priority to support junior, tenure-track investigators, or considers time-relevant issues for specific projects. As IRBs do not typically address issues of between-study competition,15 the RRRC involvement is important to navigate the challenges of registry access.
page on the Frontiers website (www.FrontiersResearch.org) to inform investigators about this resource, with links to the RRRC request form. An important metric to determine success of the registry is the number of participants enrolled in research studies. By this measure, our program is still in early stages. We are continuing to collect metrics on successful contacts and enrollment, and to communicate with clinics and study teams on barriers or problems. While we have not yet formally surveyed investigators to gather data on whether the registry has made it easier to find and recruit patients for their studies, the fact that 19 investigators have used Frontiers for multiple studies suggests they have found it useful. Anecdotally, we have heard from investigators who have been very successful using the registry for enrollment and others who have not been successful. We will be conducting semistructured interviews with several of these study teams to identify barriers and examples of best practices for recruitment. Conclusion
Good research requires research participants. Many studies fail because they do not meet their accrual goals. We developed a research participant registry that offers willing patients, whose medical record indicates they meet specific study inclusion/ exclusion criteria, the opportunity to be contacted about studies for which they are eligible. We fully expect this registry to continue to grow and to facilitate research at our academic medical center. We also anticipate expanding its impact throughout our region. It is our hope that similar registries can be set up at other institutions using the model described here.
Future Directions
Enrollment in the Frontiers Research Participant Registry has been very successful, with over 31,000 participants in
Frontiers: Integration of a Research Participant Registry with Medical Clinic Registration and Electronic Health Records Patricia M. Kluding, Ph.D.1, Jo Denton, M.S.N.2, T. Rene Jamison, Ph.D.2, William Brooks, Ph.D.2, Karen Blackwell, M.S.2, John D. Lantos, M.D.3, Lemuel R. Waitman, Ph.D.2, Tamara M. McMahon, M.S.2, Arvinder Choudhary, M.S.4, Marjorie J. Bott, Ph.D.2, Allen Greiner, M.D.2, Susan Klaus, Ph.D.2, Amy O’Brien-Ladner, M.D.2, Lauren S. Aaronson, Ph.D.2, Jeffrey Burns, M.D.2, and Richard Barohn, M.D.2 Introduction
P
articipant recruitment is a significant challenge to the success of clinical research. Without sufficient study participants, investigators cannot meet accrual goals and studies either must be abandoned without reaching recruitment targets or prolonged.1,2 Recruitment of study participants can be facilitated by maintaining registries of people who agree to be contacted for future studies. Registries range from simple databases that include only contact information, to more sophisticated regional and national registries that include individual health information and that can be searched for individuals who meet specific study criteria.3–7 Such registries clearly facilitate recruitment, but they can be costly to develop, advertise, and maintain.3,5,6,8–11 Frontiers: The Heartland Institute for Clinical and Translational Research is an academic home for clinical and translational research, headquartered at the University of Kansas Medical Center (KUMC) and partly funded by a Clinical and Translational Science Award (CTSA) from the National Institutes of Health since 2011. The vision of Frontiers is to improve the health of the region through a novel and transformative translational research enterprise from the bench to bedside to community. In this paper, we report our experience in establishing the Frontiers Research Participant Registry and highlight the unique combination of features that differentiate it from other registries: (1) Registry enrollment is integrated into outpatient clinic registration, as all clinic patients have the opportunity to provide permission to be contacted for studies for which they are eligible; (2) The registry is aligned with the complete electronic health record (EHR) that can be searched to provide the total numbers of clinic patients who meet inclusion/exclusion criteria; (3) Investigators with IRB-approved studies can receive contact information for those patients who meet criteria and who have given permission to be contacted; (4) The registry provides a HIPAA-compliant means for investigators to contact only those potential participants who meet inclusion/exclusion criteria based on their EHR. Together, these features have yielded a highly successful program with a growing database of over 31,000 individuals who have agreed to be contacted for research recruitment. The Frontiers Research Participant Registry
Important operational components of the Frontiers Research Participant Registry are described below. The enrollment process and operation of the registry is illustrated in Figure 1.
Authorization form A single-page participant authorization form was developed by the university’s HIPAA compliance officer (current version is included in the Appendix). This “permission to contact” form provides a brief description of the registry along with privacy assurances. The form is provided to patients during check-in at outpatient clinics in the University of Kansas hospital system. A signature line indicates permission to: (1) use the enrollee’s medical information to identify if they are a potential candidate for a study, and (2) release the enrollee’s contact information to investigators with IRB-approved studies. Enrollment in the registry is documented in the billing system software (IDX GE). A checkbox is used to indicate the patient’s willingness to be contacted. Customized data entry fields indicate the date the form is presented to the patient and whether the patient agrees or declines to sign. Once the form has been presented to a patient, it is not presented again at subsequent visits. The patient receives a copy of the form, which has our contact information if they change their mind and wish to withdraw their permission. There is also a field to document whether the patient subsequently withdraws their permission (i.e., if an individual informs a study recruiter or the Frontiers office that they wish to have their name removed from the registry). The authorization form provides a default option for e-mail communications to be sent through a secured system. Individuals may select two alternatives to this default for e-mail communication: (1) to permit e-mail communication sent through unsecured systems, or (2) to decline all e-mail communications. If those lines are initialed, those preferences are indicated in the corresponding data entry fields. Tracking authorizations through a checkbox in the EHR simplified our regulatory requirements. We obtained clarification from the federal Office for Human Research Protections that because the registry is integrated into the EHR rather than maintained as a separate recruitment database, the project would not be human subjects research. Therefore, IRB approval of our registry and an IRB-approved informed consent process are not required. Data repository An integrated clinical data repository containing EHR, billing, and research data across the KUMC enterprise was developed by the Frontiers Medical Informatics core team. The Healthcare Enterprise Repository for Ontological Narration (HERON)12 is an
1 Department of Physical Therapy and Rehabilitation Science, University of Kansas Medical Center, Kansas City, Kansas, USA; 2University of Kansas Medical Center, Kansas City, Kansas, USA ; 3Children’s Mercy Hospital, Kansas City, Missouri, USA ; 4Baptist Health, Jacksonville, Florida, USA . Correspondence: Patricia M. Kluding ( [email protected])
DOI: 10.1111/cts.12309
WWW.CTSJOURNAL.COM
VOLUME 8 • ISSUE 5
405
Figure 1. Overview of enrollment and operation of the Frontiers Research Participant Registry. HERON is the Healthcare Enterprise Repository for Ontological Narration, an EHR data repository. The copyright of this figure is retained by the authors of the paper.
IRB-approved data repository that uses the i2b2 (Informatics for Integrating Biology and the Bedside) framework.13 The identified EHR and billing records are merged into an i2b2 format and stored on a dedicated server with limited access. Data are then deidentified to remove protected health information and moved to a separate dedicated server that can be browsed directly by clinical researchers. As part of the deidentification process, all dates in the EHR are shifted randomly (1 to 365 days into the past); the shift is different across records but constant within the records of each patient. Investigators within our institution use the i2b2 Query and Analysis Tool to search against the fully deidentified data in HERON. This is useful as a first step to identify the total number of individuals who meet specific study inclusion and exclusion criteria and who have enrolled in the Frontiers Research Participant Registry, and provides investigators with information on the pool of potential participants. Other relevant data sources within HERON include the Social Security Death Index (a valuable exclusion criterion), University HealthSystem consortium hospital quality indicators and statistics, university-held biospecimens, and the hospital 406
VOLUME 8 • ISSUE 5
tumor registry. These queries may be performed preparatory to research during the proposal development or grant submission phases and can be completed prior to receiving IRB approval. This includes visualizing timelines of patients’ longitudinal care records and descriptive statistics (e.g., gender, racial, vital status proportions) of the potential study cohort. Once a study is IRB approved and ready to recruit, the names and contact information of registry participants may be requested as described below. Recruitment registry request committee The Recruitment Registry Request Committee (RRRC) is the gatekeeper for requests for contact information for people who enrolled in the registry and whose EHR indicates potential eligibility for a specific study. Membership of this committee includes representation from Frontiers senior leadership, the hospital and physician practice group, the HIPAA compliance office, established investigators from multiple disciplines, and a community member. Investigators with an IRB-approved study must first search the deidentified data in HERON to determine the number of WWW.CTSJOURNAL.COM
individuals in the registry who meet the specific inclusion/ exclusion criteria for their study, as described previously. This step also allows investigators to “fine-tune” their search to best suit the specific study needs within the context of the available patient census. A request for contact information may then be submitted to the RRRC for review. If approved, a passwordprotected spreadsheet containing contact information is provided to the study team. It is important to emphasize that the spreadsheet contains contact information only of individuals who meet the predetermined criteria. Although information in the EHR is used to identify the potential participants, no specific information about medical history, birthdate, medical record number, or other protected health information is provided to the investigator. Investigators typically contact the registry participants to determine interest in the study and ask screening questions to confirm eligibility. It is at this point that investigators can request specific medical information from the participant either by self-report or through access to the EHR under normal IRB-approved procedures. Investigators are required to report back to the Frontiers RRRC on the number of individuals contacted from the list and the number enrolled in the study. If any individual asks to have their name removed from the registry, the EHR record is modified to indicate that they have withdrawn, and their name is not provided in future searches. Key Developmental Steps
Stakeholder engagement With three contributing organizations representing the university, the hospital, and the physician practice group, the negotiation of a master data sharing agreement was an essential initial step to establish the governance and security of the registry. This legal document was signed by the executive leadership of each contributing organization. Under the conditions of agreement, the university was responsible for creating and maintaining the HERON data repository and supplying the information to investigators (i.e., medical center faculty). The hospital agreed to contribute information from the EHR, and the physician practice group agreed to contribute data from the billing system. An executive committee with representation from each organization was formed to provide oversight, and a subcommittee composed of the leaders from all three parties meets monthly to provide review and set direction for the development of this campus resource. Another important step in the development of the registry was the engagement with a broad representation of institutional stakeholders at all levels to gather feedback and respond to questions or concerns. The Frontiers research participant advocate served as the initial director of the registry program, which served to promote professional integrity and transparent communication to potential research participants. Prior to implementing the registry, the Frontiers leadership team presented extensively to executive leadership of the university, hospital, and physician practice group, to investigator groups, and to clinical departments. One concern about the registry raised by physicians in early discussions was the need for a mechanism for them to be informed if their patients enrolled in a clinical trial. They were concerned that their patients might receive medication or treatment that would interfere with their standard care and present a safety issue. In response to these concerns, investigators are required WWW.CTSJOURNAL.COM
to provide the RRRC with a template letter they will use to inform participants’ health care providers about the study prior to receiving names from the registry. Pilot testing To test the Frontiers Research Participant Registry enrollment and governance processes before wide implementation, a pilot program was started in 2009 at four clinics in the KUMC system representing a diverse sample of clinical disciplines: Neurology, Pulmonary, Diabetes, and the Center for Child Health and Development. The RRRC met monthly during this period to evaluate the process and identify modifications that were needed. Formal reviews and updates to participating clinical department chairs were performed after 1 month, 5 months, and 8 months. After 1 year, the program was expanded to three additional clinics (Clinical Pharmacology, Pediatrics, and Ophthalmology), and after 2 years, the program was expanded to a total of 20 outpatient clinics. At each clinic, members of the Frontiers administrative team met with individual clinic registration personnel to provide training on the form and the process. A short summary in a FAQ format was provided to the front desk staff on procedures and how to answer common questions. Initially, registration clerks reported a burden from presenting the forms at check in, providing a copy of the signed authorization form to each patient, and documenting the signature data in the EHR. To address these barriers, forms were printed on duplicate paper to eliminate copying. The registration clerks simply give the patient one copy and send the other to the Frontiers office by internal mail using a prelabeled envelope. Frontiers staff annotate the EHR using the customized data entry fields to indicate date and permission to contact as described previously. During the first year of the pilot program, several modifications to the enrollment form were made. For example, a “yes” or “no” checkbox for agreement to be contacted for future studies was included in an early version of the form, but this was replaced with the statement: “If you do not want to be contacted about research, do not sign this form.” A Spanish-language version of the form also was developed and implemented. Growth of the registry The Frontiers Research Participant Registry has grown rapidly. Within 5 years of starting the pilot program, more than 31,000 people were enrolled (Figure 2). Approximately 1,000 new enrollment forms are received each month from the clinics. Use of the registry by investigators has grown with the increased number of individuals enrolled in the registry, as illustrated in Table 1. As of January 2015, the RRRC has reviewed and approved requests for contact information from 47 different investigators for 67 distinct study protocols. These investigators represent multiple departments as illustrated in Figure 3. Lessons Learned
The development and implementation of the registry represented a significant investment from the CTSA leadership, especially the Medical Informatics, Regulatory, Community Engagement (Community Partnership for Health) and Ethics cores and the Clinical and Translational Science Unit (CTSU). Once the registry was implemented, it was essential to identify a director within the leadership of these cores who would continue to be responsible for the maintenance and growth of the registry. VOLUME 8 • ISSUE 5
407
Figure 2. Cumulative enrollment for Frontiers Research Participant Registry 2009–2014.
Figure 3. Number of requests received each year from principal investigators (# PIs) representing multiple departments (# depts) for study recruitment using the Frontiers Research Participant Registry 2009–2014.
Year
Number of names provided to study teams*
Number of registry participants contacted†
Number of registry participants enrolled‡
2009
42
15
4
2010
66
12
0
2011
676
179
15
2012
3,745
1,041
146
2013
3,892
781
13
2014
11,988
1,514
39
Totals (to end of 2014)
20,409
3,542
217
*The names provided are people who meet all inclusion/exclusion criteria based on their current EHR and who have agreed to be contacted for research purposes. † Not all names provided are contacted for a variety of reasons—study may close, participants may not respond, or contact information may have changed. ‡ Investigators provide final numbers on number of registry participants enrolled after the study closes, so 2013 and 2014 reports are incomplete as many of those studies are still active.
Table 1. Utilization of the Frontiers Research Participant Registry by investigators.
Resources Financial and personnel resources are required to support and grow the registry, including the director position, medical informatics support, and administrative support. While registry enrollment status is automatically added to the HERON system as part of the monthly processes that add billing records, medical informatics also provides participant information to study teams following RRRC approval in the role as an honest broker, and provides technical or system support. We have found that approximately 0.75 FTE of additional administrative support is needed to maintain the registry. These activities include communication with the clinic registration/front desk personnel, processing the enrollment forms and data entry to indicate registry enrollment, providing administrative support to the RRRC review meetings, responding to investigator questions about the registry, and providing assistance with performing and refining the HERON queries. Contact is made with each clinic at least once each month to reinforce the importance of their efforts for clinical research and to ask if they need additional forms or envelopes. Repeated training is required due to staff turnover or other administrative changes in the enrollment process. While the Frontiers program has supported the registry to date, other sources of support are being explored to ensure 408
VOLUME 8 • ISSUE 5
sustainability of the registry. These include partial support from infrastructure grants, like the current CTSA grant and other Frontiers resources, general institutional support, and use of charge-back mechanisms similar to other core resources at academic health centers. Authorization form and e-mails After the pilot testing, the authorization form did not change significantly for the first 4 years of the program. However, we noted an increasing interest in e-mails as a preferred means of contact for potential research participants. After extensive legal consultation, the revised form now lists e-mail address as one type of contact information investigators would receive, with an opt-out option (see Appendix). We now are able to provide e-mail contact information for new enrollees. However, acquiring this permission from the 31,000 past enrollees who signed the previous form presents a significant logistical challenge that we have not yet solved. An additional challenge with e-mails arises from our current university policy that requires e-mails with protected health information to be sent through a secure system. As this system requires recipients to create a user name and password to access the e-mail content, it is a significant barrier to communication. WWW.CTSJOURNAL.COM
This policy is currently being examined with a view to allowing e-mail sent through a nonsecure system if individuals give their permission. Therefore, this item was included on our revised authorization form. RRRC review The majority of RRRC requests are approved without concern, after verification of IRB approval and refinement of HERON search results. There have been some situations where different study teams requested participants with similar characteristics, and this has been handled with different strategies. In some cases, the second request was delayed until recruitment for the first study was completed to avoid frequent contacts of registry participants with competing study requests. Alternatively, the principal investigators of the competing studies have been asked to find a mutually acceptable compromise particularly in situations with PIs from the same department or who are collaborating colleagues, as the value of continued collaboration and collegial relationships has been noted to provide an incentive for compromise in these situations.14 To date, these types of conflicts have been rare and handled on an individual basis. However, as the registry program grows we anticipate an increased number of potential conflicts. It may be appropriate to institute a priority scoring system that incorporates a rating of scientific merit, assigns higher priority to support junior, tenure-track investigators, or considers time-relevant issues for specific projects. As IRBs do not typically address issues of between-study competition,15 the RRRC involvement is important to navigate the challenges of registry access.
page on the Frontiers website (www.FrontiersResearch.org) to inform investigators about this resource, with links to the RRRC request form. An important metric to determine success of the registry is the number of participants enrolled in research studies. By this measure, our program is still in early stages. We are continuing to collect metrics on successful contacts and enrollment, and to communicate with clinics and study teams on barriers or problems. While we have not yet formally surveyed investigators to gather data on whether the registry has made it easier to find and recruit patients for their studies, the fact that 19 investigators have used Frontiers for multiple studies suggests they have found it useful. Anecdotally, we have heard from investigators who have been very successful using the registry for enrollment and others who have not been successful. We will be conducting semistructured interviews with several of these study teams to identify barriers and examples of best practices for recruitment. Conclusion
Good research requires research participants. Many studies fail because they do not meet their accrual goals. We developed a research participant registry that offers willing patients, whose medical record indicates they meet specific study inclusion/ exclusion criteria, the opportunity to be contacted about studies for which they are eligible. We fully expect this registry to continue to grow and to facilitate research at our academic medical center. We also anticipate expanding its impact throughout our region. It is our hope that similar registries can be set up at other institutions using the model described here.
Future Directions
Enrollment in the Frontiers Research Participant Registry has been very successful, with over 31,000 participants in
