The Clinical Research Coordinator (CRC) is responsible for conducting clinical trials using good clinical practice[1] (GCP) under the auspices of the Principal Investigator (PI). Good Clinical Practices Principles have been defined by Madelene Ottosen, RN, MSN, of The University of Texas Health Science Center at Houston [2] as:
- All trials are conducted ethically, as defined by the Declaration of Helsinki, rigorously, as defined by the International Conference on Harmonization Guidelines (ICH).[3]
- Benefits outweigh risks for each patient.
- Rights, safety and well-being of patients prevail over science.
- All available non-clinical and clinical information on any investigational agent can support the trial as designed.
- All trials are scientifically sound and clearly described.
- All clinical trials have current Institutional Review Board approval.
- Medical decisions and care are the responsibility of qualified health care professionals, specifically physicians and, if applicable, dentists.
- Everyone involved in the clinical trial is qualified by training, education and experience.
- Informed consent is given freely by every participant.
- All study documentation is recorded, handled and stored to allow accurate reporting, interpretation and verification.
- Confidentiality of subjects is respected and protected.
- Investigational products maintain Good Manufacturing Practice in storage, manufacturing and handling.
- Systems to ensure quality are implemented in all aspects of the trial.
Although the PI is responsible for the conduct of the trial, “it has been said that the CRC is the heart and soul of the research study and that, ultimately, it is the CRC who carries forward the research goals, thereby playing a significant role in the success of the research study. Most importantly, CRCs are often involved in essential duties that have been traditionally performed by the PI, such as conducting the informed consent process and ensuring compliance with the protocol”.[4] The CRC’s primary responsibility, as with all clinical research professionals, is the protection of human subjects, but the CRC has many other responsibilities. Although not inclusive, some of the CRC responsibilities include preparing the Institutional Review Board submission, writing the informed consent document, working with the institutional official in contract negotiations, developing a detailed cost analysis, negotiating the budget with the Sponsor (i.e. pharmaceutical company or granting agency), subject recruitment, patient care, adverse event reporting, preparing the case report form (CRF), submitting CRFs and other data to the Sponsor as necessary and study close-out.
Contents
- 1 Responsibilities
- 1.1 Institutional Review Board submissions
- 1.2 Informed consent
- 1.2.1 Basic elements
- 1.2.2 Additional elements
- 1.3 Contracting with pharmaceutical companies
- 1.4 Cost analysis and budget negotiations
- 1.5 Subject recruitment
- 1.6 Patient care
- 1.7 Adverse events
- 1.8 Case report forms
- 1.9 Study close
- 2 See also
- 3 External links
- 4 References
Responsibilities
Institutional Review Board submissions
For more details on this topic, see Institutional Review Board.
All research involving human subjects must be approved by an Institutional Review Board. Each IRB has requirements for protocol submissions which usually require the preparation of an IRB application and informed consent document. A study cannot begin unless IRB approval is obtained.
Informed consent
The IRB must approve the informed consent prior to study initiation and often the CRC is liaison between the IRB and the sponsor. The sponsor will have set requirements of the informed consent as does the IRB. Each local IRB is responsible for the review and approval of the informed consent, but the CRC is responsible for the communication between the IRB and the sponsor. §46.116 of the Code of Federal Regulations outlines the elements of informed consent as:[5]
Basic elements
- A statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures which are experimental;
- A description of any reasonably foreseeable risks or discomforts to the subject;
- A description of any benefits to the subject or to others which may reasonably be expected from the research;
- A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject;
- A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;
- For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained;
- An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject; and
- A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.
Additional elements
When appropriate, one or more of the following elements of information shall also be provided to each subject:
- A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable;
- Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent;
- Any additional costs to the subject that may result from participation in the research;
- The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject;
- A statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject; and
- The approximate number of subjects involved in the study.
Contracting with pharmaceutical companies
The site conducting the clinical trial will negotiate the clinical trial agreement (CTA) to conform to its policies and procedures. The resolution of many contractual issues requires coordination between the sponsor, the PI and the site, which is usually the responsibility of the CRC. The involvement of each party is essential to a successful CTA with mutually acceptable terms. The CTA should include terms for indemnification, confidentiality, publication, intellectual property, insurance, data safety and monitoring boards, subject injury, governing law and termination clauses.
Cost analysis and budget negotiations
To develop a cost analysis, the CRC will review the protocol schema and determine which procedures are standard of care versus research. The research charges will be included in the budget along with personnel effort, site initiation costs, IRB fees throughout the life of the clinical trial, pharmacy costs, travel costs for the PI and CRC to attend Investigator meetings, equipment, dedicated fax and computer lines, supplies, screen failures, subject stipends, subject travel costs, and any other items that are defined as a direct cost to the clinical trial. In addition, if the clinical trial is conducted at an Academic Medical Center (AMC) there will be an indirect cost rate that will be applied to the direct costs of the study. The indirect rate is approximately 30% for pharmaceutical trials and can be upwards of 50% for federal trials, depending on the AMC’s federally negotiated indirect costs rate [1].
Subject recruitment
Prior to agreeing to conduct the clinical trial, the CRC (and the PI) will determine if they have the appropriate patient population. The CRC is responsible for subject recruitment once the trial begins or establishing the research team that will recruit subjects. It is important that viable subject recruitment occurs beforehand as the clinical trial agreement will stipulate the number of subjects the site is required to recruit.
Patient care
The CRC will coordinate and conduct patient care visits and assure all procedures are conducted in compliance with the protocol. The CRC will interact with the PI to assure patient receives appropriate medical evaluation and care when needed and will alert the PI of any serious adverse events that may occur throughout the course of the study.
Adverse events
Main article: Adverse event
An adverse event is described as “any adverse change in health or "side-effect" that occurs in a person who participates in a clinical trial while the patient is receiving the treatment (study medication, application of the study device, etc.) or within a pre-specified period of time after their treatment has been completed.” The CRC must report all adverse events to the sponsor and all serious adverse events to the IRB and sponsor.
Case report forms
Main article: Case report form
The purpose of the case report form (CRF) is to collect relevant data in accordance with the protocol and in compliance with regulatory requirements. The CRC will collect the data on the CRF and submit to the sponsor either electronically or paper format.
Study close
In accordance with the local IRB, the CRC will complete IRB study close documentation and make any appropriate notifications to the study subjects, research team, and pharmacies. The CRC will work with the sponsor’s clinical monitor in completing outstanding monitoring findings and queries. In addition, the CRC is responsible form complying with the record retention policies of the Food and Drug Administration (FDA), the ICH, and the clinical trial agreement.
See also
- Adverse event
- Case report forms
- Clinical investigator
- Clinical monitoring
- Clinical trial
- Clinical trial protocol
- Data monitoring committees
- Declaration of Helsinki
- Food and Drug Administration
- Good clinical practice
- Good manufacturing practice
- Informed consent
- Institutional Review Board
- Medical research
- New investigator
- Nurses
- Principal investigator
External links
- Good Clinical Practice in FDA Regulated Clinical Trials
- International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use
- Code of Federal Regulation §46.116 General Requirements for Informed Consent
- Association of Clinical Research Professionals
- Society of Clinical Research Associates
- Clinical Research Resources (Organizations, Services, Training)
- United States Department of Health and Human Services, Office for Human Subjects Protections (OHRP)
- OHRP Institutional Review Board Guidebook
- Indirect Cost Overview
References
- ^ http://www.fda.gov/oc/gcp
- ^ Ottosen, M. J. (2007). Clinical Research in Clinical Practice, Making it Work for Patients (presentation). The University of Texas Health Science Center at Houston.
- ^ http://www.ich.org
- ^ Fedor, C.A., et al. (2006 Remedica). Responsible Research A Guide for Coordinators. ISBN 1-901346-68-4
- ^ http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.116
