The Mid-Atlantic Twin Registry (MATR) is a population-based registry of twin pairs ascertained from birth records and the school systems of Virginia, North Carolina, and South Carolina. Located in the Office of Research at Virginia Commonwealth University (VCU), the MATR is one of the largest twin registries in the world and includes birth record data from approximately 300,000 identical and fraternal twin pairs born between 1915 and 2007. The distribution of sociodemographic characteristics of these twin pairs is representative of the characteristics in the respective states (Table 1). The MATR has enrolled more than 50,000 preschool, school age, and adult twins. By registering, twins and their family members have indicated a willingness to consider participating in health-related research.
|Table 1: General demographic characteristics of the catchment area of the Mid-Atlantic Twin Registry|
|Percent African American||19.6||21.6||29.5|
|Percent High School Graduates, age 25 and older||42.2||40.0||36.9|
|Median Household Income, 1997 model-based estimate||$40,209||$35,320||$33,325|
|Percent Living Below the Poverty Line, 1997 model-based estimate||11.6||12.6||14.9|
|Twin Birth Rate per 100||1.37||1.42||1.35|
|Estimated Number of Twin Pair Births per Year||1,000||1,250||600|
The MATR maintains contact with its membership through biannual newsletters and other mailings that convey information of special interest to twins. These mailings also serve as a method for us to obtain updated address information on MATR members. Updating and verifying twin addresses is an ongoing process that is critical to the viability of the MATR.
2.0 RESEARCHER ACCESS
Access to data from MATR twins is available to researchers from outside of VCU on a limited scale, according to the demand made on MATR participants and MATR staff by current and upcoming projects. The MATR welcomes proposals from investigators seeking to include MATR participants in their research. The liaison for this process is either the MATR Scientific Director or the MATR Administrator. The MATR Administrator will respond to all such inquiries and work with researchers to answer their questions and to help guide feasible projects through the application and review process. Although the MATR will try to expedite requests to the greatest possible degree, applicants should be aware that some lead time is necessary for a proposed project to be reviewed, approved, and implemented. Past studies have shown that a period of 6 to 12 months from time of initial contact to approval and implementation can be typical. The process includes submission of an application and review by the MATR Executive Committee (MEC). The MEC reviews all research applications for access to the MATR with regard to human subject’s protections, subject burden and scientific merit and then decides whether a project should be approved or disapproved. Decisions are made based on a voting process in which majority rules. The MEC meets as needed according to applications received. Review may take place by telephone, email or at a scheduled meeting of the MEC.
|Table 2. Typical time line for project application and review process|
12 to 9 months from grant submission deadline
Initial contact with MATR
9 to 6 months from deadline
6 to 3 months from deadline
2.1 SAFEGUARDING PARTICIPANT DATA
Because the MATR's continued success rests on the participation of its registrants, we are vigilant about protecting participants' rights to privacy and the confidentiality of the data they provide. Thus, the MATR releases personal identifying information to outside investigators only when absolutely necessary for the conduct of an approved research project. For example, if a study is collecting data via written questionnaire and blood samples for DNA analysis, the MATR will collect these data on behalf of the investigator. The data provided to the investigator will be identified using unique numbers assigned to each biological sample and completed instrument. No personal identifying information will be released. For protocols that require direct interaction with MATR participants, the MATR will make initial contact with eligible participants (or in the case of subjects under age 18, with parents or legal guardians) to gain their consent to be contacted by the investigator. Once this consent is obtained, the MATR releases encrypted subject contact information to the investigator.
All researchers who access MATR data or collect data from MATR participants are expected to observe professional standards of confidentiality at all times. Researchers should hold any personal identifying information they may receive as privileged and confidential data. In many cases, the MATR may request that the investigator obtain a Certificate of Confidentiality from the U.S. Department of Health and Human Services, to provide additional protection of participant data. Participant data is not to be released to any third party without the prior written authorization of the MATR. In cases of complaints of unethical practices by an investigator who is contacting MATR participants, the MATR will contact the appropriate authorities (Institutional Review Board officials) to request an investigation that could result in the study being halted. If the complaint is verified, the MATR will deny that investigator further access to the registry.
Data collected or accessed for a specific study is to be used solely for that study and not beyond the scope of the project. All personal identifying information (PII) from MATR participants enrolled in the study must be returned to the MATR or anonymized, obliterated, or otherwise destroyed, with the investigator providing a letter certifying the destruction or return of the information. PII must be returned to the MATR when no further contact is required with that participant. Depending on the study protocol, need for continued participant contact may cease mid-way through the project or continue to the end of the funded period. Schedules for the handover of participant PII can be developed according to each project's protocol. This policy enables the MATR to "release" a participant from a particular study and, after an appropriate respite period, deem that participant approachable for invitations to participate in other studies. The MATR's provision of additional subject pools for new initiatives or the investigator's use of previously provided subjects in a continuation of an ongoing study must be negotiated on a study-by-study basis.
2.2 APPLICATION AND REVIEW PROCESS
We recommend that investigators contact the MATR Administrator with requests for access as early as possible: during the conceptual phase of the project is ideal. This contact will generate a dialogue about the project that will be helpful to both the investigator and the MATR. Certain projects may require contact with a population difficult to track or data collection methods previously untested with MATR participants. Preliminary discussion of these issues can help determine whether the project is feasible.
2.2.1 PRELIMINARY APPLICATION PROCESS.
The researcher must submit a two- to three-page letter of intent summarizing the project, typically no later than six months prior to the due date for a grant or competitive renewal application related to the project. Upon receipt of the letter of intent, the MATR Administrator will contact the investigator to schedule a meeting at the MATR offices for a presentation of the proposed project and further discussion with the Co-directors and MEC. The investigator will meet at least once with the MATR Co-directors and Administrator to discuss the project. During this meeting, the MATR Co-directors will determine the role that the MATR will play in the proposed study (collaborator versus service provider (see 2.1.2)), and they may recommend that a preliminary data analysis be conducted to determine if the MATR has sufficient data/participants to support the project. The MATR charges the investigator an hourly fee for this preliminary analysis.
2.2.2 DETERMINATION OF MATR ROLE IN PROJECT.
Requests for access to the MATR typically fall into two broad categories. These include projects for which MATR Directors are active collaborators. For such projects, direct contact with MATR participants typically is necessary. The second category of participation involves projects in which the MATR acts as a service provider and contacts subjects and/or collects data and/or biological samples on behalf of the investigator. No direct contact between the investigator and the participants is necessary for such projects.
22.214.171.124 MATR AS A COLLABORATOR IN THE PROPOSED RESEARCH.
If the MATR assumes the role of a collaborator, at least one of the Co-directors will serve as a co-investigator on the project. For such protocols, the MATR will make the initial contact with eligible subjects on behalf of the investigator to inform them of the study, invite their participation, and obtain their consent to be contacted by the investigator's team. The MATR will then provide contact information for willing participants to the research team.
126.96.36.199 MATR AS A SERVICE PROVIDER.
As service provider, the MATR will act on behalf of the investigator at a level of activity appropriate to the project, as agreed by the MATR and the investigator. MATR personnel will assist investigators in one or more of the following ways:
- Announce the study in one or more issues of the MATR biannual newsletter and/or on the MATR web site
- Include study screening items in regular surveys or phone interviews conducted by MATR personnel
- Act on behalf of the investigator to coordinate the collection of study data and/or biological samples and provide this information to the PI without personal identifying information.
2.2.3 FORMAL APPLICATION AND REVIEW PROCESS.
Once the groundwork for a project is laid through the informal process, an investigator can enter into the formal approval process, which includes review of a research application (see Appendix) by the MATR Executive Committee (MEC). Applications are required for either new or continuing studies and should be made a minimum of three months prior to the submission of any new grant or competitive renewal application.
The MEC consists of:
- The VCU Chair of Human Genetics
- The MATR Principal Investigator (PI)
- Senior Human Genetics Faculty
- The MATR Administrator
- Other twin researchers as needed
The following factors are considered in decisions regarding MATR access:
- The scientific merit of the proposed project.
- The compelling need to use twins to accomplish the specified scientific aims.
- The level of subject burden imposed on MATR participants. Typically, access is granted only to projects that present no more than a minimal risk to subjects. In addition, the MATR will not ask its participants to enroll in more than one study at a time.
- The privacy implications of the project to potential participants.
- The project’s contribution to a balanced research portfolio for the MATR.
- The principal investigator’s record of peer-reviewed publications related to the subject.
- The availability of funding and the potential of the project to generate long-term, significant federal or private/corporate funding for further study.
- The current level of demand on MATR staff by other research projects.
- The potential for overlap with the ongoing twin research program of the Department of Human Genetics, through which this research resource (the MATR) was developed.
Applicants will be notified in writing of the decision within two weeks of the MEC meeting date. All decisions are final and can be appealed only by revising and re-submitting the application. Access to the MATR is granted only for the duration of data collection or funding, whichever ends first. Any MATR data made available for or collected through a proposed research project are for use solely in the specific study and are limited solely to the scope of the study as it was reviewed and approved during the application process.
3.0 REQUIREMENTS FOR BEGINNING AN APPROVED PROJECT
Several requirements must be met before the MATR will begin to identify eligible participants or select required data to begin a project that has been approved for access
3.1 PROOF OF HUMAN SUBJECTS PROTECTION REVIEW
No research project shall be initiated without proof from the investigator that the project has received approval from the researcher's institutional review board (IRB). A copy of the approval memorandum from the appropriate IRB and a copy of all IRB-approved consent forms must be submitted to the MATR Administrator. Depending on the nature of the protocol, it may also need to be reviewed and approved by the IRB of the MATR's home institution, Virginia Commonwealth University (VCU), or a cooperative amendment (CA) may be established between VCU's IRB and the investigator's IRB. If VCU IRB review is required and the investigator is not from VCU, the IRB package will be prepared by the investigator but must be submitted through one of the MATR Co-directors or the Administrator. (VCU investigators will submit their protocols to the VCU IRB according to established IRB guidelines.) Submission to the VCU IRB may be coordinated through the MATR Administrator. If a cooperative amendment (CA) is to be established, the MATR Administrator will initiate the steps to establish this amendment through VCU's Office of Research. This agreement recognizes the investigator's IRB as the IRB responsible for approving the protocol, meaning that the protocol need not be reviewed by the VCU IRB. These amendments are filed with The Office for Human Research Protection. The decision as to whether or not a protocol requires additional review by the VCU IRB or if a CA should be arranged will be handled by the MATR Administrator, who will discuss the matter with the VCU Office of Research and VCU IRB officials. This decision is based upon the nature of the protocol and the level of the MATR's involvement in the project.
If the MATR and the researcher have determined that a Certificate of Confidentiality can be obtained for the study, the investigator must provide a copy of the certificate or a copy of the paperwork submitted to obtain the certificate before the MATR will begin work on the project.
3.2 SUBMISSION OF DATA COLLECTION INSTRUMENTS AND PROTOCOLS
The investigator must provide the MATR Administrator with a copy of all data collection instruments, interview scripts, and tissue collection protocols. These materials will be reviewed by the MEC during the application process. However, the MATR must keep copies of all final, IRB-approved materials on file, to help the MATR respond to questions from participants regarding the study or related issues. In addition, the MATR will request to review all data collection instruments prior to their final production to ensure that they conform to MATR formatting requirements (i.e., the MATR name/logo must be included on all data collection instruments that study participants see).
3.3 SUBMISSION OF SIGNED AGREEMENT
Each investigator who is granted access to the MATR signs a formal "researcher agreement" delineating his or her responsibilities to the MATR in accordance with these guidelines. Issues specific to each research project will be itemized in this agreement.
3.4 PAYMENT OF FEES
The investigator must have made a partial or full payment for the project or issued a contract promising payment before the MATR will begin work. Payment schedules will be negotiated on a project-by-project basis.
4.0 REQUIREMENTS FOR USERS
During the conduct of a project and at its conclusion, researchers are expected to comply with the following rules.
4.1 NOTIFICATION OF UPDATED CONTACT INFORMATION
The MATR is responsible for tracking all MATR subjects who might be lost to follow up. If the investigator requires updated contact information, the MATR will provide it to the principal investigator within 4 weeks of the MATR's discovering new contact information. If investigators become aware of new contact information for MATR participants during the course of the study period, this information should be reported to MATR personnel within two weeks.
4.2 NOTIFYING MATR OF MEMBER RESPONSE TO RECRUITMENT ADS
In some cases, the MATR acts as a service provider by publishing recruitment advertisements in its newsletter or on its web page, or by direct mailings to targeted MATR participants. In these situations, the investigator is expected to notify the MATR when a MATR registrant contacts the investigator in response to the recruitment effort, providing the subject's name, address, and telephone number. By providing this information in a timely manner, the investigator helps the MATR staff to avoid contacting such subjects to participate in other research projects. The MATR has found, through polling a representative sample of its members, that members want to be contacted no more than twice a year with invitations to participate in research, and many do not want to be contacted when they are already involved in a study.
4.3 NOTIFICATION OF DEVIATION FROM PROTOCOL OR UNANTICIPATED RISKS TO SUBJECTS
The investigator is expected to report immediately to the MATR administrator or directors any deviation from MATR protocol that occurs during the course of the study, whether unintentional or required by study circumstances. Similarly, any discovery of unanticipated risks to subjects or adverse events must be reported immediately.
4.4 NOTIFICATION OF SUBJECT REQUEST TO WITHDRAW
The principal investigator will notify MATR personnel within 24 hours when a MATR participant expresses a desire to withdraw either from the specific study OR from the MATR. MATR personnel will contact these individuals to clarify the nature of their refusal and whether and in what way they wish to be contacted by the MATR.
Annual and final reports provided by investigators enable the MATR to provide an accurate accounting of study activities to its grantors and to MATR participants.
4.5.1 ANNUAL REPORT
All principal investigators must submit an annual progress report to the MATR detailing the previous year’s activities. Since projects have different start dates and may be linked to reporting periods established by granting agencies, a unique due date for this report will be established for each project and stipulated in the research contract. Annual progress reports submitted to the project’s funding agency are acceptable as long as they include the components in the list below. It is acceptable to submit the funding agency progress report with attached pages responding to any components below not addressed in the funding agency progress report:
- Progress in relation to original project time line
- Number of subjects participating in the study
- Accounting of instances in which participating twins did not receive promised results of tests they have undergone for the study
- List of presentations at professional conferences or publications in refereed journals arising from the project (or papers in manuscript form being prepared for submission to a journal)
- Problems or difficulties encountered, including any variations from MATR protocol outlined in these guidelines and in the researcher agreement, and solutions to these problems
Investigators are also asked to provide three copies of any reprints of articles published in relation to research using data from MATR participants. The MATR may also ask an investigator to provide, on an annual basis, a brief summary of the project suitable for publication in the MATR newsletter.
4.5.2 FINAL REPORT.
In addition, the investigator is responsible for providing MATR personnel with a final progress report summarizing activities of the entire project within four months of completing the study.
4.5.3 REPORTS OF STUDY PROGRESS TO PARTICIPANTS.
The MATR will inform participant families at least once per year via an edition of its newsletter of all findings related to the study or studies conducted with MATR participants.
4.6 CONVEYANCE OF MATR DATA
At the termination of data collection or grant funding for the project, whichever occurs earlier, names and identifying information of MATR participants, if provided to the investigator, must be returned to the MATR. Personal identifying information in all computer and hard copy files must be obliterated or the files must be destroyed. These measures are required to enable the MATR to maintain its promise to its participants that all possible steps are taken to protect the confidentiality of their identity and data.
Many protocols may require that study participants be contacted only once or twice during the duration of the project, but plan for data collection to occur over several years, such that, for example, data collection for one-third of study participants will be completed in the first year of the project, for another third, in the second year of the project, etc. For protocols such as these, the MATR will request that the PI return contact information to the MATR on a revolving basis, for example, returning participant PII on a monthly or quarterly basis. The purpose of this policy is to make MATR participants available to be approached with invitations to participate in new studies, after they have undergone an appropriate respite period. The principal investigator may coordinate with the MATR Administrator and/or Data Base Administrator the schedule for the return of participant PII or date(s) when PII is to be returned (or purged from the PI's files). Depending on the nature of the study, this schedule may be outlined in the research agreement. For data purges, written documentation (typically in the form of a letter) certifying the data purge must be submitted to the MATR Administrator. The investigator shall make no further contact with the MATR participants released for the specified study without prior written approval from the MATR. The MATR's provision of additional participant pools to the investigator is to be negotiated on a study-by-study basis.
To minimize subject burden and to add to the value of the MATR as a future research resource, the MATR may ask investigators to share results of certain analyses of biological samples collected as part of the study. For example, if zygosity assays are conducted as part of the study, investigators may be asked to report the results of these assays to the MATR. The consent form for the study must inform participants which data will be shared with the MATR. Such requests will be reflected in the researcher agreement (see 3.3). The cost for collecting samples and conducting these assays, whether incurred by the investigator or the MATR, will be taken into account by the MATR when study-specific fees are negotiated. In such situations, consent forms for these studies must clearly indicate to study participants that the MATR will receive results of a certain test or analysis.