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ClinicalTrials.gov

Over the past two decades, government agencies and the International Committee of Medical Journal Editors (ICMJE) have issued laws and directives on the subject of clinical trial registration. All parties have consistently agreed that the purpose of trial registration is to promote the public good by ensuring that the existence and design of clinical trials are publicly available. The registration effort began with the development of a publicly available website, ClinicalTrials.gov, a service of the National Institutes of Health (NIH), developed by the National Library of Medicine.

In 1997, the Food and Drug Administration (FDA)/NIH began requiring registration for only a limited number of trials. Then in September 2007, the FDA Amendments Act (Title VIII. Sec. 801) significantly expanded the scope of clinical trials that must be registered and set civil monetary penalties for failing to register “applicable trials.” In 2004, the ICMJE defined trials that must be registered in order to be considered for publication in journals that adhere to ICMJE standards. In 2007, the ICMJE expanded the definition of trials that must be registered. Scores of journals (not limited to medical journals) have adopted the registration policy. In 2016, the final rule for Clinical Trials Registration and Results Information Submission (42 CFR Part 11), which clarifies and expands the requirements in FDAAA 801, was released, and the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information was published.

The bottom line:
The FDA, NIH and the ICMJE each have their own requirements for registration, and while some of the requirements overlap, there are some differences. In order to comply with the law and preserve the ability to publish in many journals, all sets of requirements must be met. UConn Health is committed to supporting Principal Investigators (PIs) with meeting the requirements concerning the public availability of clinical trial data in ClinicalTrials.gov, as outlined in our University ClinicalTrials.gov policy.

How is “clinical trial” defined and what are the registration deadlines?

According to NIH:

A clinical trial is a research study1  in which one or more human subjects2 are prospectively assigned3 to one or more interventions4 (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.5  All clinical trials must be registered within 21 days of enrollment of the first participant.

1See Common Rule definition of research at 45 CFR 46.102(d).

2See Common Rule definition of human subject at 45 CFR 46.102(f).

3The term “prospectively assigned” refers to a pre-defined process (e.g., randomization) specified in an approved protocol that stipulates the assignment of research subjects (individually or in clusters) to one or more arms (e.g., intervention, placebo, or other control) of a clinical trial.

4An intervention is defined as a manipulation of the subject or subject’s environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints.  Examples include:  drugs/small molecules/compounds; biologics; devices; procedures (e.g., surgical techniques); delivery systems (e.g., telemedicine, face-to-face interviews); strategies to change health-related behavior (e.g., diet, cognitive therapy, exercise, development of new habits); treatment strategies; prevention strategies; and, diagnostic strategies.

5Health-related biomedical or behavioral outcome is defined as the pre-specified goal(s) or condition(s) that reflect the effect of one or more interventions on human subjects’ biomedical or behavioral status or quality of life.  Examples include:  positive or negative changes to physiological or biological parameters (e.g., improvement of lung capacity, gene expression); positive or negative changes to psychological or neurodevelopmental parameters (e.g., mood management intervention for smokers; reading comprehension and /or information retention); positive or negative changes to disease processes; positive or negative changes to health-related behaviors; and, positive or negative changes to quality of life.

Registration Deadline: The NIH Policy on Dissemination of NIH-funded Clinical Trial Information applies to applications for funding submitted to NIH on or after 1/18/17. Registration is required no later than 21 days after the first patient is enrolled. The consent form for the trial is required to include the following language: “A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law.  This Website will not include information that can identify you.  At most, the Website will include a summary of the results.  You can search this Website at any time.”

According to the ICMJE:

A clinical trial is any research project that prospectively assigns people or a group of people to an intervention, with or without concurrent comparison or control groups, to study the cause-and-effect relationship between a health-related intervention and a health outcome. Health-related interventions are those used to modify a biomedical or health-related outcome; examples include drugs, surgical procedures, devices, behavioral treatments, educational programs, dietary interventions, quality improvement interventions, and process-of-care changes. Health outcomes are any biomedical or health-related measures obtained in patients or participants, including pharmacokinetic measures and adverse events. Those who are uncertain whether their trial meets the expanded ICMJE definition should err on the side of registration if they wish to seek publication in an ICMJE journal.

Registration Deadline: Registration at or before the time of first patient enrollment is as a condition of consideration for publication in an ICMJE journal.

According to the FDA:

The U.S. Department of Health and Human Services in September 2016 issued a final rule that specifies requirements for registering certain clinical trials and submitting summary results information to ClinicalTrials.gov. The new rule expands the legal requirements for submitting registration and results information for clinical trials involving U.S. Food and Drug Administration-regulated drug, biological, and device products. The FDA Amendments Act (Title VIII. Sec. 801) requires registration for all “applicable clinical trials,” regardless of funder, that are:

  1. Trials of drugs and biologics: Controlled, clinical investigations, other than Phase I investigations, of a product subject to FDA regulation, and
  2. Trials of devices: Prospective clinical studies of health outcomes comparing an intervention with a device against a control in human subjects (other than small clinical trials to determine the feasibility of a device, or clinical trials to test prototype devices where the primary outcome measure relates to feasibility and not to health outcomes); and pediatric postmarket surveillance studies, as required under the Federal Food, Drug and Cosmetic Act.

Registration Deadline: The FDA Amendments Act of 2007 requires that all trials, regardless of sponsor, must be registered in full no later than 21 days after the first patient was enrolled.

Who is responsible for registering a trial?

The PI is ultimately responsible for determining that registration requirements are met. Although some industry sponsors will do the actual registration work, it is still the PI’s responsibility to ensure that the registration has been accomplished and is accurate.

What are the penalties for failing to register?

According to the ICMJE:

Unregistered trials will not be considered for publication in journals that adhere to ICMJE standards. Questions about policies of a specific journal should be addressed to that journal directly.

According to the FDA/NIH:

Penalties may include civil monetary penalties up to $14,724 fine for failing to submit or for submitting fraudulent information to ClinicalTrials.gov. After notification of noncompliance, the fine may go up to $14,724 per day until resolved. For federally-funded grants, penalties may include the withholding or recovery of grant funds.

Who can help with questions about meeting the requirements?

To comply with University policy regarding ClinicalTrials.gov, please direct any questions to the local Protocol Registration and Results System (PRS) Administrator for UConn/UConn Health, Ellen Ciesielski, Research Integrity & Compliance. The local PRS Administrator serves as a point of contact for resolving requests by ClinicalTrials.gov and regularly monitors to promote compliance with the requirements.

 

 

IACUC Membership

    1.       PURPOSE

    1.1          This policy establishes the responsibilities and roles of IACUC members, as well as the processes to add and remove an IACUC member to the roster.

    2.     IACUC MEMBERSHIP

    2.1  IACUC members shall be selected in accordance with Public Health Service Policy on Humane Care and Use of Laboratory Animals Policy IV.A.3, IV.B., and IV.A.C , Animal Welfare Act Regulations 2.31, and the “IACUC Constitution and Function” detailed in The Guide for the Care and Use of Laboratory Animals. PHS policy is regulated by the Office of Laboratory Animal Welfare (OLAW) and the Animal Welfare Act is regulated by the United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS).  IACUC members will be selected based on qualifications, education, and/or experience and a positive attitude toward IACUC membership.

    2.2  Membership is contingent upon commitment to items listed in section 2.4 of this policy and subject to review by the IACUC executive staff (Institutional Official [IO], IACUC Chair,  IACUC Vice Chair, and the Director). Scientific members shall be appointed to a 3-year term subject to the above-mentioned annual performance review.  Appointments can be renewed.  IACUC members shall inform the IACUC Administrator by email that they accept their appointment when they receive the appointment letter from the IO.

    2.3  Program Responsibilities of the IACUC as defined by the above regulations

    2.3.1     Ensure compliance with all regulatory agencies and AAALACi
    2.3.2    Semi-annual review of the program and inspection of all facilities and prepare reports of results to the Institutional Official
    2.3.3    Review of all activities involving live animals
    2.3.4    Review, and investigate if necessary, all concerns involving live animal care and use.
    2.3.5    Making recommendations to the Institutional Official regarding any aspect of the animal care and use program
    2.3.6    Suspending activities as required
    2.3.7    Oversight of training programs related to animal care and use
    2.3.8   Oversight of occupational health and safety protocols related to animal care and use
    2.3.9   Oversight of policies pertaining to animal care and use
    2.3.10  Meeting as necessary to ensure required activities occur
    2.3.11  Advise on facility security as related to animal care and use
    2.3.12  Advise on emergency and disaster planning as related to animal care and use
    2.3.13  Conduct post-approval monitoring activities

    2.4   Individual IACUC member responsibilities

    2.4.1    Review all materials provided for IACUC meetings
    2.4.2    Familiarize yourself with all protocols on he agenda for a full committee review (FCR)
    2.4.3    Declare any potential conflict of interest related to their work on the IACUC; if there is a conflict of interest during review, recuse yourself from the vote
    2.4.4    Be aware of federal regulations in the Animal Welfare Act, Title 7, Chapter 54, section 2157 – it is unlawful for any member of an IACUC to release confidential information to a third party or to use, or attempt to use, confidential information to their own advantage.
    2.4.5    Complete all training and continuing education sessions as assigned by the IACUC Administrator
    2.4.6    Attend a majority of the scheduled committee meetings
    2.4.7    Demonstrate a professional and courteous manner towards other members, staff, and faculty.
    2.4.8    Familiarize yourself with applicable policies, regulations, and guidelines given to you in your “IACUC Member Handbook”.
    2.4.9    Act as a liaison for your colleagues
    2.4.10  Complete all assigned protocol reviews by the due date assigned by the IACUC administrative staff. If you cannot, contact the IACUC Administrator so another reviewer can be assigned.

        2.5   Individual IACUC member rights

        2.5.1    Request FCR for any animal activity for any reason within the timeframe given to you.
        2.5.2   Voice a minority opinion for the record related to any topic covered in the semi-annual report to the IO.
        2.5.3   Participate in any scheduled facility inspection or program review activity.
        2.5.4   Raise policy issues to the Committee for discussion

          2.6  Expectations of Committee members at meetings

          2.6.1    Share your unique input to get all the issues “on the table”. Members are expected to be active participants in IACUC discussions; for instance, if you have information that has not been discussed, share it.
          2.6.2   Think critically but fairly and use the criteria for approval (Appendix I) to decide whether to approve the research. If you have a concern, problem, or recommended change, be able to base it on the criteria for approval.
          2.6.3   Listen and learn from the group but think and vote independently.   Vote according to your own conscience in an informed manner.
          2.6.4   Respect minority opinions when offered.
          2.6.5   Remember that all discussions and Committee decisions are considered confidential.
          2.6.6   Understand that Committee decisions are made by majority rule and not consensus.

            2.7   IACUC Chair

            2.7.1   Responsibilities
            2.7.1.1   Assigns/Approves reviewers for protocols meeting the criteria for a Designed Member Review
            2.7.1.2   Signs OLAW Inter-Institutional Assurances
            2.7.1.3   Runs the IACUC meetings
            2.7.1.4   Has the authority to make exemptions to IACUC Policies
            2.7.1.5   Assigns members to subcommittees when required
            2.7.1.6   Any other as defined by laws, regulations, guidelines, or policies
            2.7.2   The IACUC Chair should normally be an IACUC member who is a respected individual with knowledge of research ethics, regulations, and guidance that govern animal research.
            2.7.3   The IACUC Chair will be appointed to a 3-year term.

            2.8   IACUC Vice Chair

            2.8.1   Responsibilities
            2.8.1.1   Discharge the IACUC Chair’s responsibilities when the Chair is unable to do so
            2.8.1.2   Discharge the responsibilities assigned by the IACUC Chair
            2.8.1.3   Assist in the operation of the IACUC
            2.8.2   Appointment of the Vice Chair is made by the IACUC Chair and the IACUC Administrator wit the approval of the IO.
            2.8.3   The IACUC Vice Chair should commit to a 3-year appointment unless renewed or appointed to become IACUC Chair, thereupon the responsibilities and appointment term will be exclusive as defined above.

              3.       Process for Appointment of IACUC Members

              3.1    Process of nomination of new members
              3.1.1    The IACUC Chair, Vice Chair, Director, and/or Administrator identify and nominate an individual for a vacancy on the IACUC.
              3.1.2   The IACUC Administrator obtains the resumé or curriculum vitae of the nominee and forwards to the IACUC Chair and IO for review
              3.1.3   If all parties agree that the background of the potential member is a good fit with the current membership of the IACUC, an interview (telephone, web, or in-person) will be conducted with the IACUC Chair, Vice Chair, Director, Administrator, and the IO.
              3.1.4   After the interview, a decision by all parties will be made regarding the appointment.
              3.1.5   Once the nominee has been appointed, the IACUC Administrator prepares and appointment letter which is signed by the IO and send to the individual.
              3.1.6   Once the nominee has accepted the appointment, a meeting will be held between the new member and the IACUC Administrator who assigns any training and provides the individual with an “IACUC Member Handbook”. Training, documents given, etc. are all recorded on a new member orientation form held by the IACUC office. The individual is added to the IACUC roster.
              3.1.7   The new IACUC member is assigned a mentor – typically, a seasoned IACUC member who will help guide the new member with regard to protocol reviews and provide any other help the new member may need.

              3.2    Process for reappointment of members
              3.2.1   Members are appointed to a three-year term, subject to annual continuation. After the annual evaluation of the member (see section 2.2 above), if all parties agree the member should continue for the next year, a continuation appointment letter will be prepared by the IACUC Administrator and sent to the IACUC member.

              4.       Process for Removal of IACUC Members

              4.1    The IO or their designee is responsible for deciding whether to remove an IACUC member.
              4.2   If the IACUC member will no longer serve as an IACUC member, the IACUC administrator will prepare a thank you letter which will be signed by the IO and sent to the member.
              4.3   The membership roster will be updated as required.

               

              Effective Dates:                 December 5, 2024 through December 31, 2027

              Appendix I:

              Criteria for Reviewing Animal Care and Use Protocols

              Compiled from regulations set forth from:

              * Animal Welfare Act (Title 7, Chapter 54, United States Code)

              * Animal Welfare Regulations (9 CFR, Chapter 1, subchapter A, parts 1-4)

              * PHS Policy on the Humane Care and Use of Laboratory Animals

              * US Government Principles

               

              I:  Selection and Justification of Species

              • The animal model selected should be the most appropriate species for the project based upon anatomical, physiological, or other characteristics in consideration of the scientific objectives and the need to obtain valid results

              II:  Living Conditions of the Animals

              • The living conditions of the animals must be appropriate for their species and contribute to their health and comfort
              • Any deviations from standards set forth by the Guide and the USDA regulations must be scientifically justified and approved by the ACC

              III:  Justification for the Use of Animals

              • Procedures involving animals should be designed and performed with due consideration given to their relevance to human or animal health, the advancement of knowledge, or the good of society
              • Protocols involving animals should have sound research design and should yield valid results
              • Projects must not unnecessarily duplicate previous experiments and any duplications must be justified

              IV:  Application of the Principles of Replacement, Reduction, and Refinement

              • Replacement: when objectives can be achieved using reasonably available non-animal models, the alternative should be used
              • Reduction: the number of animals used should be the minimum necessary to achieve scientific goals
              • Refinement: procedures should be used that have the least amount of potential pain, discomfort, distress, or morbidity

              -PI must provide a written narrative describing the methods and sources used to determine that alternatives to painful/distressful procedures were not available:

              Database search* (must be >1) if utilizing USDA-regulated species must include:

              Databases searched
              Date of search
              Years covered by search
              Search strategy used

              *Other sources consulted (e.g., experts in field, standard reference books, etc.)

              V:  Ethical Cost-Benefit Relationship

              • The ethical cost of the research must be outweighed or balanced by the potential value of research to human or animal health, the advancement of knowledge, or the good of society

              VI:  Treatment of Pain and Discomfort

              • Unless the contrary is established, investigators should consider that procedures that cause pain or distress in human beings may cause pain or distress in animals
              • Procedures that cause more than momentary pain or distress must be performed with state of the art sedation, analgesia, or anesthesia unless withholding is justified for scientific reasons
              • Pain alleviating agents should be administered as part of a continuum when appropriate

              VII:  Post-Procedure Monitoring

              • All animals must be monitored at appropriate intervals dictated by the nature of procedure, degree of potential pain, possible complications of the procedure
              • During monitoring, animals should be evaluated for the presence of pain, discomfort, or distress
              • Observer should use criteria based upon the normal behavior pattern of the species
              • Simple observation by a skilled observer can reveal a great deal of information

              VIII:  Restraint

              • Mechanical restraint must be justified
              • Unacceptable to use mechanical restraint on awake animals if non-mechanical forms can be used
              • Device must provide the animal with the opportunity to assume its normal postural adjustments
              • Animals should be conditioned to the device
              • Duration of restraint must be minimized
              • Animal should be observed at appropriate intervals

              IX:  Euthanasia

              • Method of euthanasia should be based upon the species, the size of the animal, the scientific objectives of the experiment, and its ability to quickly and painlessly produce a loss of consciousness and death
              • Euthanasia must comply with current (2000) American Veterinary Medical Association Panel on Euthanasia Guidelines

              X:  Qualification of Research Personnel

              • Personnel who perform procedures involving live animals must be
                – Knowledgeable about the biology of the species being used
                – Fully qualified by training and experience to carry out their assigned duties
              • Any individual who lacks the prerequisite qualifications must be trained before they interact with animals

              XI:  Occupational Health and Safety

              • The ACC must be satisfied that there is an effective occupational health and safety program for all individuals using laboratory animals
                – Ensures risks associated with experimental use of animals are reduced to acceptable levels
                – Ensures personnel are appropriately trained with the use of any hazardous agents

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              EH&S Policies, Regulations and Guidance

              Biological

              General

              Radiation Safety Training Requirements

              UNDER NO CIRCUMSTANCES WILL AN INDIVIDUAL BE ALLOWED TO WORK WITH RADIOACTIVE MATERIALS PRIOR TO RECEIVING THE APPROPRIATE RADIATION SAFETY TRAINING

              The United States Nuclear Regulatory Commission’s regulations mandate radiation safety training for all personnel working with radioactive materials. UConn Health is committed to providing a safe research and work environment to all our faculty and staff. The Office of Radiation Safety provides training lectures to meet this requirement.

              It is the Principal Investigator’s responsibility to insure that:

              • New personnel who will be working with radioactive materials, using the
                Cs-137 Gammacell Irradiator or working in areas where radioactive materials are used and/or stored attend the four hour Initial training lecture.
              • Personnel who have received training over a year ago attend a Refresher lecture.

              Other personnel wishing to review and update their radiation safety training are invited to attend.

              Education and Information

              The Office of the Vice President for Research is responsible for assessing and addressing the education and information needs of UConn staff and faculty involved in sponsored research and compliance activities across UConn’s schools and colleges on all University campuses.

              This section of the website provides educational information and support including tutorials, manuals, job aides, videos, and other reference guides to help and support faculty, staff, and students.

              Learn something new everyday!