Operation Of The Repository

Who Is Involved

As the sponsor of the repository, Accelerated Cure Project is responsible for the design, operation and funding for the repository. We rely on our top-notch scientific advisory board for scientific guidance and review. The actual specimen and data collection process is conducted at enrolling sites across the country. In addition, we have engaged three primary vendors, SeraCare BioServices, Document Solutions Group, and Omnicare Clinical Research to assist us with the sample processing and storage, data management, and site management tasks, respectively.

Design And Preparation Of The Repository

Sample kit

In deciding what samples to collect, we consulted with our scientific advisory board and other experts. The major points of consideration were which types of samples would be most useful to the research community and would maintain integrity during storage. We also needed to consider the limits to the amount of blood that can be drawn from an individual in this type of study (110 milliliters for adults 18 years and older, lesser amounts for children and adolescents).

We then worked with SeraCare BioServices, Inc. to further refine the kit contents and to define the processing and shipping procedures needed to ensure the highest quality of the samples.

For the main study, we have also built some flexibility into the kit and are able to modify the kit composition (by adding one or more tubes) to respond to specific research proposals.

Case report form

Our data collection instrument, the case report form (CRF), was also developed in consultation with our scientific advisory board. We undertook a fairly extensive process of asking other scientists for their questionnaires, laying all the options out, and deciding which questions made the most sense in our context. Our pilot project helped us identify questions that were and were not working well. In addition, from our experiences on the pilot study which used a paper CRF, we decided to utilize electronic data capture (EDC) in lieu of a paper CRF for the main study.

When a paper CRF is used, the study coordinator at a site interviews the subject and fills in the answers. The CRF is then sent to a data management company where it is scanned and checked for errors. Any errors that are found are sent back to the site. The study coordinator then must contact the subject to resolve the issue. It can take days, weeks or months to get all of the issues resolved and the data "clean." EDC, however, results in cleaner data more quickly because the subject's responses are entered in real time into a computer which has been programmed to check the answers as they are entered.

We selected Document Solutions Group (DSG) as our EDC vendor and have worked together to convert our paper questionnaire into a computer based CRF. DSG has designed and implemented the software necessary to check the subject's answers as they are entered during the interview. DSG also performs the rest of the data management tasks associated with the repository -- storing of all of the anonymized subject data, distribution of data upon request, and others.

Site selection

During the process of refining the kit and CRF for the main study, we started thinking about "where" to collect the samples and data. With an initial goal of 1,000 subjects in 18 months, we decided to select between five and ten sites, each having a sizeable patient population with MS and the related demyelinating diseases. We documented the other requirements that a site would have to meet in a site information document (SID).

Once we had selected a number of potential sites, we began working with our vendor, Omnicare Clinical Research (OCR) to finalize the selection process and to establish budgets and letters of agreement (LOA) with each site. Template files for the budget and LOA are customized for each site.

Site approval and activation

To participate in our repository, sites must receive approval to enroll subjects and have the necessary regulatory documents in place. For example, each participating site has had an Institutional Review Board approve the protocol, informed consent form, and any additional materials given to the subject.

Each site has also received training on the protocol, collection, and shipping procedures from SeraCare BioServices, and on the use of the EDC system from DSG.

Site monitoring

Each enrolling site participates in bi-weekly monitoring calls with the OCR site monitor. During these calls, the site monitor and the study coordinator discuss how the study is progressing at the site. They review any personnel changes that have occurred at the site, address any factors that are affecting the site's ability to enroll, and discuss any issues associated with the protocol, EDC system, etc.

Recruitment And Collection Process

Pre-screening and preparation

Enrolling sites conduct a pre-screening process by evaluating their current patients against the inclusion/exclusion criteria and determining which of their patients may be eligible for participation in the repository.

Those patients are approached and provided with an IRB approved copy of the informed consent document, a paper copy of the case report form and an IRB approved copy of any pre-visit checklists that site personnel have prepared to instruct the patient what they would need to bring to a study visit.

Some sites also display or send out IRB approved advertisements or flyers to attract interested potential subjects.

Informed consent

Prior to performing any study procedures, the principal investigator or study coordinator conducts the consent process by reviewing the written form with the subject and also giving an oral description of the procedures. Once potential subjects have had all of their questions answered and feel as though they fully understand what participation in the study means, they may choose to give their consent or choose not to participate. If they do wish to participate they must sign the informed consent form, if they can, or provide oral consent to a witness who will then sign the form for them.

A copy of the signed informed consent form is given to the subject, a copy of the signature page is made for Accelerated Cure Project, and the original consent form is kept in the subject's study file.

Subject confidentiality

Each collection kit used in the repository is marked by SeraCare with a unique alphanumeric barcode which will become the unique identifier for a subject. All collected samples and data are marked with that barcode in lieu of the subject's name.

In order to establish the link between the subject's identity and his/her barcode, the study coordinator fills out a confidential contact sheet (CCS) which documents the barcode and the subject's contact information. This allows the subject to be contacted in the future by the site in order to participate in the longitudinal visits. The site makes a temporary copy of the CCS (which they will only keep for six months) and sends the original to Accelerated Cure Project where we keep the information in a secure location.

Because we at Accelerated Cure Project maintain the link between the subject's identity and this original barcode, a second barcode is also generated by SeraCare for each subject. This secondary barcode and its link to the first barcode are known only by SeraCare and DSG personnel (who have no knowledge of the link between the first barcode and the subject identity). The DSG system holds the link between these two barcodes and presents the second barcode as the subject identifier when anyone from Accelerated Cure Project logs into to the EDC system. This prevents the stored data from ever being associated with a subject's identity.

Sample and data collection

The study coordinator uses the tubes in the collection kit (currently nine tubes that contain up to 66 ml of blood for adults) to collect blood from the subject. These tubes are marked with the subject's barcode and date and time of draw, processed according to the specimen handling instructions and shipped to SeraCare for further processing and storage.

The study coordinator also interviews the subject and completes the CRF on the computer. During this interview, the study coordinator collects information about the subject's environmental, geographical and medical history, demographic data, and current clinical status. All data is stored at DSG under the assigned barcode.

If the subject is unable to complete the entire interview during that first visit, the site can complete the interview during a later visit, provided that a minimum subset of questions needed to characterize the blood sample itself have been answered on the day of the blood draw. Sites are encouraged to complete the interview with the subject as soon as possible to minimize the need for follow-up.

During the interview, any discrepancies or errors in the entered data will be caught by the EDC software. In addition, after the data is entered into the system, it reviewed for completeness and correctness by OCR and Accelerated Cure Project staff.

The site coordinator next gathers all supportive diagnostic reports (MRIs, lab reports, etc.) from the subject's medical records. These reports are anonymized at the site, marked with the subject's barcode and sent to OCR where they are scanned and uploaded into the EDC system.

As the last step in the data collection process, the enrolling physician completes the last several pages of the CRF which document how the subject was diagnosed with his/her disease and the results of standard clinical tests and assessments that have been performed for that subject.

Referral of relatives and others to participate

All cases are asked to refer others to the study based on the control hierarchy. Essentially, we seek to enroll any affected blood relatives, any identical siblings (affected or unaffected) and then one or two first degree blood relatives (parents, siblings, etc.). If a subject does not have any available blood relatives to refer, he or she may be asked to refer a closely matched unrelated friend.

When the subject's referrals are enrolled into the study, the site coordinator fills out the participant unit form via the EDC system which links the subject's barcode with the barcodes of their referrals. If any referrals also meet the case inclusion criteria of this study, their barcodes are also entered into new PUFs so that they may then refer their relatives and other controls.

All subjects are reimbursed a site-specific nominal amount for time, travel, transportation, etc.

Longitudinal follow-up

Repository participants are contacted by site personnel approximately every 1-2 years for a follow-up visit which may include additional blood draws, a new CRF interview and/or the updating of medical status. As indicated in the informed consent, the subject may elect to not participate in these follow-up visits.

Sample And Data Distribution

Written proposals are initially reviewed by ACP staff for completeness, alignment with the goals of the repository, and our ability to fulfill the request. Any issues with the proposal are conveyed to the investigator who is given an opportunity to make changes.

The proposal is then reviewed by the repository oversight committee which assesses the proposal against a variety of factors including the scientific merit of the application and the potential benefit to people with MS and related diseases. The committee then makes a recommendation regarding whether to approve the sample request.

ACP makes a final decision on providing the samples and associated data and communicates that decision to the investigator.

Investigators who receive samples from the repository agree to submit their data generated from use of the specimens back to the repository for incorporation into the sample database.

Review the application procedure, proposal form, and sample material transfer agreement.

Learn more about the available samples.