NIH’s genetic info data system goes on-line
System was launched this spring
The Genetic Modification Clinical Research Information System (GeMCRIS), a web-based data system designed to assist researchers and others involved in human gene therapy studies, manages information about science and safety of clinical trials in this field.
Three years in development, the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) jointly launched GeMCRIS at the end of March.
"There were several reasons for developing GeMCRIS," reports Allan Shipp, director of outreach in the Office of Biotechnology Activities at NIH.
"It gives the government agencies that have oversight in this area a tool to do cross-cutting analyses," he adds. "So it helps us do our job of oversight of safety."
Investigators involved in human gene transfer protocols conducted at institutions with NIH funding for recombinant DNA research already are required to register with NIH. With GeMCRIS, they may electronically report their AEs to NIH through an AE-reporting module, says Kelly Fennington, project officer at NIH.
"When a principal investigator [PI] reports an adverse event, the system is loaded with information about the protocol so that the principal investigator doesn’t have to retype that information," she says.
NIH and FDA officials worked collaboratively to develop an adverse reporting format that investigators and sponsors can use to report AEs. This form contains data elements agreed upon by both NIH and FDA so investigators can use one form to report to two federal agencies. This form also can be faxed or sent to their IRBs, their data safety monitor boards (DSMBs), institutional biosafety committees (IBCs), and other oversight bodies, Fennington explains.
The system does permit PIs to delegate the AE reporting to a clinical trials coordinator or to someone else involved with the study, Shipp notes.
"But we expect a signed letter of delegation, and we hold the principal investigator responsible for whether the information has been reported," he says.
Designed to make AE reporting easier
A key role of GeMCRIS is to facilitate AE reporting, making it easier for investigators to adhere to the requirements that serious adverse events are reported on an expedited basis, Shipp notes.
"Serious adverse events that are unexpected and thought to be related to the gene transfer intervention have to be reported within 15 days of a principal investigator’s notification of a sponsor or within seven days if the event is life-threatening or involves death," he says.
"A registered principal investigator would have a user ID and password and would go to our secure GeMCRIS site," Shipp explains.
Once the identification information is typed in, the system presents the investigator with a form that asks for all of the information that is required by the NIH and FDA agencies, he adds.
NIH beta-tested GeMCRIS for a year before launching the system publicly, Fennington says.
So far, the feedback has been positive, Shipp reports. "We received feedback that helped in designing the system in the beta-testing, including its ease of use as a reporting tool," he says. "As we developed this system, we conducted focus groups with different potential end users: one for investigators, one for patients, one for IRB/IBC members."
GeMCRIS also provides the public access to a rich set of data about gene transfer trials.
Clinical trials subjects, their families, investigators, IRB members, and others may see everything collected in the system except for the raw adverse event data. There is no need for registration or a password to access this public information, Shipp notes.
"Previously, we had information about trials in our system, but it wasn’t in an interactive data-base," he says. "It was a very rudimentary data-base, and the information was more limited than what you see in the GeMCRIS."
Once someone visits the web site, it’s a simple matter of going through the site’s search engine in GeMCRIS and then selecting from the available data, Fennington says.
Researchers, patients, and others are able to pull up information about clinical applications; investigational strategy, including what vector is used; the gene transfer product; route of administration; a scientific abstract that allows one to view the overall scientific strategy, and a nontechnical abstract that is written at a level that could be understood by an educated layperson, Shipp says.
For example, a clinical trial listed on the site for gene therapy to treat prostate cancer offers these descriptions in the scientific and nontechnical abstracts:
- Scientific abstract: "Direct introduction of therapeutic genes into malignant cells in vivo may provide an effective treatment of solid tumors such as adenocarcinoma of the prostate. The herpes simplex virus thymidine kinase (HSV-tk) gene codes for an enzyme which phosphorylates the nucleoside analog ganciclovir (GCV) into an intermediate that is incorporated into newly synthesized DNA and terminates further replication, leading to cell death. . . ."
- Nontechnical abstract: "Direct introduction of therapeutic genes into tumor cells may provide an effective treatment of prostate tumors. One strategy is to confer drug sensitivity to tumor cells by inserting a recombinant gene into them. This gene is from the common herpes virus and codes for the enzyme thymidine kinase (HSV-tk). Thymidine kinase converts the antiviral drug ganciclovir into a form that is toxic to rapidly dividing cells such as tumor cells."
GeMCRIS has several features that make it easy for investigators or their clinical trials representatives to report AEs.
For instance, when an investigator types in an ID number and password, the pre-formatted report pops up with all of the information that already has been reported about the particular trial, Fennington explains.
After the initial AE report has been filed, an investigator may return to GeMCRIS to type in follow-up information. "The previous adverse event information pops up, and all they have to do is type in information that has changed," she says.
If an investigator is interrupted in the middle of filing a GeMCRIS AE report, then it’s possible to click on a "pending" icon so that the report is saved, but not entered as final data until the investigator returns and completes the report, Shipp says.
Another value of GeMCRIS is that it allows for reporting and analysis of adverse events in a more standardized way. Prior to GeMCRIS, adverse events were submitted in various formats and could not be standardized for analysis, he explains.
"Often, they were reported on MedWatch forms or templates or the back of a cocktail napkin or whatever," Shipp says.
Since the reporting previously was so open-ended, NIH officials often had to call investigators to obtain necessary details, he adds. "Through standardized vocabularies and data elements, reports are clearer and are more easily compared and analyzed."
It’s a much richer data set than can be worked through in such a way that yields much more helpful information, tailored to the information needs of end users, Shipp notes. "GeMCRIS is an important new tool to make investigators’ lives easier and to help us do our jobs better."