Conducting clinical research
International expectations for conducting clinical research are outlined in the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) document on Good Clinical Practice (PDF - 380 KB), particularly, in sections 4, 5, 6, and 8.
Further, the FDA describes the responsibilities of clinical investigators in Title 21 Part 312 Subpart D of the Code of Federal Regulations. The FDA has additional guidance documents related to Good Clinical Practice and maintains regulatory enforcement lists.
Investigators are required to report adverse events to Institutional Review Boards and appropriate regulatory authorities. Expedited reporting procedures exist for events that are considered serious and unexpected. ICH’s Clinical Safety Data Management E2A (PDF - 147 KB) defines a serious event as any untoward medical occurrence that meets any of the following criteria:
- Results in death
- Is life threatening
- Results in hospitalization or prolongs ongoing hospitalization
- Results in persistent or significant disability or incapacity
- Is a birth defect or congenital anomaly
FDA IND Safety Reporting Regulations require reporting of all adverse events with the time frame dependent upon the nature of the event.
General guidance is also available in the NIH Notice on Adverse Event Safety Reporting to IRBs and in the Office for Human Research Protection Guidance on Adverse Event Reporting. In addition, NIH-sponsored clinical research that uses genetically modified material for human gene transfer has a dedicated adverse event reporting mechanism, which is available through the GeMCRIS Web site.
Upon completion of a study, the investigators analyze the results and prepare a study report that includes data and conclusions. ICH also provides guidance on the preparation of study reports (PDF - 471 KB).
Monitoring clinical research
Studies are also monitored while they are being conducted to assure that study participants are protected and to assure the integrity of the data being collected. A study that is uninformative is considered unethical because the participants will assume the risk without the benefit of the knowledge learned.
In the Good Clinical Practice Document (PDF - 380 KB) the ICH defines monitoring as “the act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded and reported in accordance with the protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirements. “
Study monitoring occurs on several levels including, but not limited to, Institutional Review Boards and regulatory authorities. Some studies are monitored by an additional independent Data Monitoring Committee. The Food and Drug Administration provides guidance on Data Monitoring Committees outlining the circumstances that may prompt the use of a data monitoring committee and recommendations on procedures and process.