Summary and quick links

What is clinical research?
Getting started in clinical research
General issues concerning clinical research
Good Clinical Practice
SOM Clinical Trials Office (CTO)
     Support for clinical investigators
     Support for clinical research coordinators (CRCs)
     Mentoring for CRCs and investigators
     Monitoring of clinical trials
     Quality assurance
     Orientation Manual (intranet)
Cancer Center Office of Clinical Research:  ( description/ web site)
Investigational Drug Service
School of Medicine Clinical Research Unit 
Institutional Review Boards (description/web site)
     Federal Wide Assurance information for UVA IRBs 
Biostatistical support (Dept. of Public Health Sciences, Division of Biostatistics & Epidemiology)
Phlebotomy and specimen processing services
Resources for research subjects
     Participating in clinical research at UVA (VP for Research site)
      Current clinical trials at UVA (as posted on clinicaltrials.gov)
Protocol development
Accessing clinical services and laboratories
Publishing clinical trials to web sites
Contracts and clinical trials agreements

What is clinical research? The NIH Director's Panel on Clinical Research 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, which are codified in the Nuremberg Code, Declaration of Helsinki, Belmont Report, and in federal regulations, 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, including 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 (UVA policy on the electronic storage of highly sensitive data), U.S. Food and Drug Administration (FDA) rules, restrictions on financial conflicts of interest, etc.

The conduct of human subjects research is a partnership between investigators and the clinical research staff.  The expertise and dedication of the Principal Investigator (PI) to the research project is of overriding importance.  However, successf ultimately depends on a clinical research coordinator (CRC), who interacts 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 defined by guidelines 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 just below) offers GCP training for clinical coordinators and investigators.

SOM Clinical Trials Office (CTO). The CTO supports clinical trials in several areas, as 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.  The CTO supports investigator-initiated research by helping with submission of 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 refer to 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 CRCs via a continuing education series, "brown bag" sessions, external audio conferences, and Tips of the Month.
• Monitoring of clinical trials.  The CTO offers monitoring services and training for new monitors working with UVA investigators who have assumed the role of sponsor (as defined by the FDA) for a clinical trial.
• Quality assurance.  The CTO maintains Standard Operating Procedures for the conduct of clinical trials.  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.

Cancer Center Office of Clinical Research (OCR). This Cancer Center office provides centralized support for the conduct of cancer clinical trials at the Health Sciences Center.  Its principal goal is to assist UVA physicians and nurses in the collection of data that are accurate, unbiased, and well-organized.  OCR also supports the Cancer Center Protocol Review Committee, which provides scientific and clinical review of in-house and industry-supported clinical protocols and ensures that all protocols meet the ethical standards of the University and are appropriate for the patient populations served by the Cancer Center.  The OCR also publicizes active protocols to attending and referring physicians and alerts physicians to patient eligibility, whenever appropriate, for particular protocols.

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 x2-1048.

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 the 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.  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, on a fee-for-service basis, process specimens that require special handling or will be sent to UVA research laboratories.  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 (CTO) can access current hospital laboratory charges for the development of budgets and can develop a billing plan delineating the procedures and interventions to be performed during the study as 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 (x2-4383).