Conducting Post Market Registries – Rationale and Execution (Part 2)

10 June, 2015, by ClinCaptureTeam

In this paper, we aim to educate around the different types of registry studies, and some of the specifications in its execution. This paper was written by Clinovo’s founder and President Ale Gicqueau, for the 2015 Association of Clinical Research Professionals (ACRP) Global Conference and Exhibition.

Ethics, Data Ownership, and Privacy

The principles of ethics, data ownership and privacy are the same for registry studies as they are for clinical trials. IRB approval is required to conduct the study, HIPAA waiver to access patient medical records, a financial agreement with the institution regarding payments, data ownership and publication rights, and assurances of patient privacy.

Recruitment

Recruitment of sites becomes a major issue in studies the breadth of registries. Sites should be paid fair-market value for their time and must see a benefit to their operations if they are to join and actively participate in a registry. This is especially true if the registry study is to include community physicians or high-volume specialty centers, as well as academic centers. Community physicians are more likely to participate if the registry is viewed as a scientific endeavor, is endorsed by leading organizations, led by a respected opinion-leader, provides useful self-assessment data to the physician, or helps meet other physician needs such as maintenance of certification, credentialing, or pay-for-performance programs.

Patient recruitment presents the same challenges as clinical studies. The best success comes from recruitment by the patient’s own physician. It also helps to communicate that registry participation may help improve care for future patients, to provide written materials in language easily understood by the lay public, keep survey forms short and simple, and provide incentives such as newsletters, reports, and modest monetary compensation.

Data collection and quality assurance

Three sets of documents, together, form the system for data collection. The first is the case report forms, and there is no reason to stay with paper today with the new appearance of low-cost cloud-based EDC solutions. The eCRFs are the forms whereby data is gathered in the field, entered into coded database fields, and stored in a clinical database. The second is a data dictionary, which contains a detailed description of each variable used in the registry.

Monitoring

Observational still require to be monitored. A monitoring plan is developed for a registry study the same way than a clinical study. At the minimum, monitors have to verify that: 1) the subject exists, 2) has the disease or condition under study, 3) met inclusion and exclusion criteria, 4) signed an informed consent and HIPAA authorization, 5) received or declined treatment.

Adverse event reporting

For device and device procedure registries, adverse event detection, collection, and reporting is the same as adverse event reporting for any other post-approval setting. The time required to report adverse events starts at the moment the investigator becomes aware of symptoms or events reported by the patient. Investigators must report serious injuries to manufacturers and to FDA within 10 days. Investigators are responsible to report deaths to both the manufacturer and FDA as soon as possible but within 10 days. If an adverse event occurs with a comparator device the investigator must also report the event to the comparator’s manufacturer. Manufacturers have 30 days to report deaths, serious injuries and malfunctions to FDA, and 5 days to report events that require remedial action to prevent an unreasonable risk of substantial harm to the public health.

Analysis and Interpretation

Statistical analysis of registry data is no different than statistical analysis of clinical data. There are a couple of points that are different. First, we have to determine how closely the actual study population represents the target population. Second, there should exist a statistical analysis plan for how the data are to be analyzed and interpreted with regard to accepting or refuting the hypothesis. And third, there should exist a plan for how to handle missing data.

Selecting a clinical database for post market registries

New tools have been emerging that allow companies embarking on trials to do a lot of the work themselves. In the past, life science companies had to pay a CRO, software vendor, or other professional services provider to perform functions such as changing case report forms from paper to electronic. The trend now is to provide free or inexpensive software along with do-it-yourself capabilities that allow even small companies to do much of the work themselves.

 The Database chosen must have the ability to be configured easily, FDA part 11 compliant, and capable of collecting large samples of data. EDC software with the same capabilities as the more expensive systems has come down in price dramatically. In some cases, the software is even free. This has happened for two reasons. The costs for supplying cloud software are far reduced from the traditional licensed delivery model that existed in the past. Today we also have a validated regulatory environment in the cloud, whereas in the past companies had to establish their own data center and validate it at a high cost. All of this is causing a dramatic drop in the initial entry cost (the license and startup cost) for starting a trial.

ClinCapture is one such database, with a scalable, and configurable system that allows you to design the database and configure it without expert knowledge of programming and IT. Additionally, they have an innovative business model where the use of the database in its standard version is absolutely free up to 500 CRFs. This is very helpful as post-market registries have smaller budget than randomized clinical trials.

With this new generation of cloud-based EDC, there is no more reason to stay on paper. It has been proven that EDC cut in half monitoring costs for any clinical study thanks to remote monitoring, fewer site visits, shorter patient recruitment times, reduction (or elimination) of printing costs, faster data entry, and lower data cleaning costs. Time-saving is also not negligible. Single data entry—which replaces the completion of paper CRFs followed by double data entry—remote monitoring, and reduction in the number of queries each save a considerable amount of time. Overall, they have been calculated to reduce the duration of clinical development by up to 30%. As we saw earlier, the report of adverse events is just as critical for post marketing studies. Some specific EDC features have an even bigger impact: faster and automatic notification of adverse events, for example, can help with earlier and better decision-making, potentially saving hundreds or thousands of patients from exposure to unsafe medication.

Conclusion

Developing Registries is fast emerging as an effective means of collecting large amounts of clinical data that can be leveraged for market expansion, reimbursement, publications, and post market surveillance for safety. Choosing the most effective database will depend on the capabilities desired, but many cost effective options such as ClinCapture are available today.

End of Part 2

Ale Gicqueau,
President and Founder at Clinovo