ARG, with a history of conducting successful retrospective studies in several therapeutic areas, has identified several critical success factors.
Identifying Critical Success Factors in Retrospective Studies
Retrospective studies look back through time using existing records to examine safety, clinical, and (healthcare) utilization data. A clear advantage for adopting this approach is that retrospective studies do not need to follow subjects into the future, which should reduce their timelines and cost. These advantages can only be realized by a sponsor partnering with a contract research organization (CRO) that has experience managing retrospective studies. Atlantic Research Group (ARG), with a history of conducting successful retrospective studies in several therapeutic areas, has identified several critical success factors.
Asking Questions About the Data
For a sponsor starting a retrospective study, the first priority should be putting together a protocol that clearly defines the data to be collected. Although this is always an important aspect in any clinical trial, taking this step early in the process can alleviate challenges during the conduct of a retrospective study. Robust feasibility must be done to confirm that sites have the data necessary for study analysis in their medical records. ARG recommends asking sites to provide an example of the data points being routinely collected, to help identify risks in data collection and interpretation.
In terms of data, a vital consideration would be to first know where the patient source documents are located, and how they will be provided to the CRO for monitoring. The following questions should be asked: Is the data electronic, and can it be downloaded to the new database for review, or, will someone need to manually enter it from paper? How can we define up-front how mismatched or missing data will be handled in the analysis (of inputted data)?
It takes an experienced and flexible CRO team to be able to deal with the myriad of possible answers. Regardless of whether the source documents are paper or electronic, the CRO needs sufficient access and the ability to evaluate completeness; in addition, the team needs to determine how long it will take to enter information into the database. Finally, ARG recommends identifying a site resource early in the process who can efficiently navigate the source documents in order to address questions and resolve queries from the CRA.
With sites, it is important to confirm the process by which data is going to be identified and collected. ARG shares lessons learned and discusses with sites how gaps will be recognized and reported. In short, a comprehensive data collection strategy should be included in the procedures manual.
Implementing Strategy from Technical to Medical
A CRO that is strategic is also an asset when building a database. ARG Data Management suggests building a database with the following flexible characteristics: naming conventions, missing data labels (not done, unknown, NA), drop down options vs. free text fields, appropriate edit checks to reduce the frequency of automatic queries, and alignment with site EMR/EHR data. To ensure the database is functioning the way it is intended, ARG employs frequent data reviews to assess data gaps, data entry, and data presentation (i.e. dry run TLFs, patient profile summaries).
A CRO with experience in retrospective studies can provide benefits to sponsors in many ways, from technical to medical. At ARG, we believe it is crucial for Sponsors to consider retrospective studies in the eCRF design. Sites could potentially be retrieving large amounts of data and possibly from years back; therefore, the eCRF design needs to reflect the same flow as medical records for ease of review and entering data.
ARG has years of chart review experience to help design the eCRF. In addition, experience in multiple therapeutic areas is very valuable in the design process. The ARG team, with expertise in rare disease trials, can both identify potential challenges in advance and adjust for the nuances that are encountered in retrospective studies. The bottom line is to work with an organization that has a proven track record of getting these kinds of studies done.
Experience allows the CRO to take steps to ease the participation burden for both patients and sites. At times, there is a prospective component to the studies. When this occurs, ARG implements tools and techniques such as electronic consent, telemedicine and patient compensation to alleviate the burdens of participation. With sites, it is imperative to minimize the burdens of time and effort. Studies can be made more convenient for sites by providing specifics about the data being collected and how to resolve questions, as well as by utilizing eSource and direct EMR/EHR access.
Matching Solutions With Challenges Via Collaboration
A key to successful retrospective studies is working with a CRO that knows how to match solutions with challenges. In one ARG study, the issue of re-consent emerged because the original study and its corresponding data was all tied to the specific site. The solution was for the site to actually monitor the subjects they were not able to re-consent, and for our team to review the re-consented subjects. This averted a slowdown and the study continued on time.
The challenges that emerge in retrospective studies can be addressed most easily by a CRO that stresses collaboration and communication. ARG is a tight organization with signature cross-functionality and group problem-solving. Being able to pick up the phone or go down the hall to ask a question can be very helpful in retrospective studies.
Since ARG stresses daily interaction to relay important study information, we are able to meet our deliverables as the needs of the sponsor change. All of this is made possible by assembling a team with members that come from all sides and sizes of the biotech and pharma industries.
At ARG, we invite you to discuss how we can use our experience and success in retrospective studies to enhance your drug and device development process by formulating a specific plan based on your needs and goals.