Clinical research
Summary and quick links
What is clinical research?
General issues concerning clinical research
Good Clinical Practice
SOM Clinical Trials Office
Support for clinical investigators
Support for clinical research coordinators (CRCs)
Monitoring of clinical trials
Quality assurance
Resources for clinical investigators and research coordinators
Professional development opportunities for CRCs and investigators (coming soon)
Clinical Trials Office Orientation Manual (intranet)
Clinical Trials Office Human Subjects Resource Guide (intranet)
Investigational Drug Service
General Clinical Research Center
Institutional Review Boards
Phlebotomy and specimen processing services
Resources for research subjects
Participating in clinical research at UVA (VP for Research & Graduate Studies)
Current clinical trials (UVA Medical Center Web site)
Current clinical trials (UVA Medical Center The Link publication)
Protocol development
Accessing clinical services and laboratories
Publishing clinical trials to Web sites
Getting started in clinical research
What is clinical research? The NIH Director's Panel on Clinical Research (1997) developed the following description:
- Patient-oriented research. Research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. This area of research includes: mechanisms of human disease; therapeutic interventions; clinical trials; development of new technologies
- Epidemiologic and behavioral studies
- Outcomes research and health services research.
Note that this definition excludes in vitro studies utilizing human tissues that do not deal directly with patients.
By contrast, "clinical trials" assess the safety & efficacy of new therapeutics, vaccines, devices, or other interventions. Clinical trials are divided into the following categories: Phase I (small numbers of healthy subjects to determine safety and appropriate dose); Phase II (larger numbers of subjects to gather preliminary evidence of the effectiveness and major side effects of the intervention; Phase III (the "gold standard" for determining the efficacy of an intervention, with collection of data on rarer side effects - for use in drug labeling if approved by the FDA); and Phase IV (post-marketing studies such as comparison with other drugs on the market, longer-term estimates of effectiveness, effectiveness in a real-world setting, or examination of very rare side effects).
General issues concerning clinical research. Safety of research subjects is paramount. Modern clinical research practice and requirements are based on rectifying the errors and horrors of the past (Tuskegee syphilis experiment, Nazi experimentation, regulatory approval of thalidomide, etc.). These requirements are codified in the Nuremberg Code, Declaration of Helsinki, Belmont Report, and in federal regulations. Briefly, these include:
- Subjects must willingly consent to participate and can withdraw from a study at any time. Special care must be taken when working with subjects with diminished autonomy.
- Clinical research must provide potential benefits to society, though not directly to the subjects.
- Experiments must be designed and conducted to avoid injury to subjects.
- Clinical research is distinct from medical care.
- Ethical committees must review, approve, and monitor research involving humans, to protect the rights and welfare of the subjects. Members weigh risks against benefits, payments to subjects, statistical power, individuals conducting the study, consent document, and so on.
Clinical research is a highly-regulated environment. Regulations include federal requirements governing Institutional Review Board (IRB) review and approval of human subjects research, Health Insurance Portability and Accountability Act (HIPAA) privacy and security requirements, U.S. Food and Drug Administration (FDA) rules, restrictions on financial conflicts of interest, and so on.
Clinical research is a partnership between the investigators and the staff conducting the research protocol. The expertise and dedication of the Principal Investigator to a research project is of overriding importance. However, successful ultimately depends on a clinical research coordinator (CRC), who handles the day-to-day interactions with research subjects, the IRB, the FDA, and sponsor (if applicable), the department finance office, clinical laboratories, and research pharmacy. CRCs are usually, but not always, trained as nurses, physicians' assistants, or nurse practitioners. Coordination and open communication between the PI and CRC are necessary in order to negotiate the clinical research process from protocol development to final reporting and publication.
Good Clinical Practice (GCP). GCP is a set of rules and regulations issued by the US Food and Drug Administration (FDA) and the International Conference on Harmonisation (ICH) covering the responsibilities of investigators and sponsors and the protection of research subjects, and providing guidelines that ensure interpretable outcomes of clinical studies. For more information, see the FDA GCP Web site and the FDA/ICH publication "Guidance for Industry: E6 Good Clinical Practice: Consolidated Guidance." The Clinical Trials Office (see below) offers GCP training for clinical coordinators and investigators.
SOM Clinical Trials Office (CTO). The CTO supports clinical trials in several areas: preparation of clinical trials proposals (including forms and budget development); study coordination; data management; quality control; and monitoring after study initiation. These are described below:
- Support for clinical investigators. For faculty performing sponsored clinical trials, the CTO develops budgets based on current charges for Medical Center services and clinical laboratories. CTO will negotiate a study budget with the prospective sponsor. Once the study is underway, the CTO will work with the study coordinator to invoice the sponsor for services performed and will monitor the trial. For faculty performing investigator-initiated research, the CTO will provide help in submitting Investigational New Drug Applications and other regulatory documentation, and development and submission of protocols and case report forms for the IRB and GCRC.
- Support for clinical research coordinators (CRCs). New CRCs should become consult the CTO Orientation Manual for information on GCP, ethics, submitting protocols at UVA, managing clinical trials, and regulatory matters. The CTO trains, mentors, and provides continuing education for UVA CRCs via annual continuing education series, "brown bag" sessions, external audio conferences, and Tips of the Month.
- Monitoring of clinical trials. The CTO offers monitoring services as well as training for new monitors working with UVA investigators who have assumed the role of Sponsor for a clinical trial.
- Quality assurance. The CTO maintains Standard Operating Procedures for the conduct of clinical trials and training and orientation of the clinical trial process for clinical research personnel. In the event that a sponsor or the FDA audits a UVA study, the CTO will assist the investigator and CRCs in preparing files for the audit visit.
Investigational Drug Service. This office, provided by the Medical Center, supports clinical drug trials from study design and submission of IND applications, to drug preparation, storage, logging, and dispensing. IDS can be contacted at 982-1048.
General Clinical Research Center. Since 1968, the GCRC has provided investigators with specialized resources necessary to conduct advanced clinical research, including ten inpatient beds, research nurses, core assay laboratory, metabolic kitchen, outpatient facilities, computing and statistical consultants and facilities, and sleep and exercise physiology laboratories. The facilty can be contacted by phone (924-2394) or e-mail (GCRC@virginia.edu).
Institutional Review Boards. The IRB-HSR (Institutional Review Board - Health Sciences Research) is responsible for review and approval of studies involving biomedical/invasive procedures, comprising the majority of clinical research initiated at the School of Medicine. The IRB-SBS (Institutional Review Board - Social and Behavioral Sciences) is responsible for approving and overseeing non-invasive studies involving human subjects (e.g., survey studies). The IRB Web site provides information on on-line applications, help in crafting protocols, and the protocol review and approval processes.
Phlebotomy and specimen processing services. Phlebotomy services are available on a fee-for-service basis through the Medical Center Clinical Laboratory at these sites: Primary Care Center 1st Floor, Barringer 3rd Floor, 415 Fontaine 2nd Floor, and Northridge 1st Floor. Phlebotomists will collect specimens but will not accept responsibility for specimen processing or transport unless the specimen is being sent to the Medical Center Clinical Laboratory. Phlebotomy services are also available for protocols that are being conducted by the General Clinical Research Center. Investigators choosing to perform phlebotomy in non-patient care areas must register with the Institutional Biosafety Committee. Specimen handling, storage, and shipping. The Biorepository and Tissue Research Facility (BTRF) will process specimens requiring special handling or that will be sent to laboratories other than the Medical Center Clinical Laboratory, on a fee-for-service basis. The investigator must transport the specimens to the BTRF. Contact Craig Rumpel, Biorepository Manager (car6m@Virginia.edu, 982-6453) to discuss anticipated costs and to arrange for accessing this service. In some instances, the BTRF may be able to arrange for sample pick-up. Investigators who process and ship their own specimens must register with and receive training from the Institutional Biosafety Committee.
Protocol development. The IRB offers help in protocol development, either directly or through IRB support personnel who are located in the various clinical departments of the medical school.
Accessing clinical services and laboratories. The Clinical Trials Office can help develop study budgets, can access current hospital laboratory charges for the development of budgets. The Clinical Trials Office (CTO) also can develop a billing plan delineating which procedures and interventions to be performed during the study will be standard-of-care vs. investigational, and who (sponsor, insurer, patient) will be financially responsible for each. The CTO can negotiate the study budget with the sponsor and can generate invoices based on the billing plan, as study milestones are achieved. Contact Katherine Richardson (982-4383).