Investigator Handbook
Chapter 2: INVESTIGATOR RESPONSIBILITIES

Be qualified by education, training and experience to lead the study.

• Be familiar with any investigative agents/devices used in the study.
• Provide or ensure adequate medical care is given to subjects (including adverse events, undercurrent illnesses).
• Ensure accountability of investigative product and proper instruction to subjects.
• Follow randomization procedures outlined in approved protocol.
• With subject permission, if appropriate, inform subject's primary physician of participation

Serve as the responsible leader of the team who directs this study.

• Ensure there are adequate resources to conduct the research, and these resources include:
  • your time to oversee and manage the study;
  • a sufficient number of qualified staff; and
  • sufficient funds to cover all services required in the study.
• Ensure the research team understands the study protocol and their responsibilities.

Conduct the study in accordance with the protocol reviewed/approved by the CPHS.

• Ensure informed consent form is approved by the CPHS, requirements for obtaining consent are met, and communication of information is documented.
• Obtain CPHS approval prior to implementing changes to the approved protocol.
  If the change prevents an immediate hazard to a patient, it is carried out before CPHS approval.
• Provide the CPHS all necessary documents, including written summaries of study and final report on the outcome of the study.
• Explain all study deviations to the CPHS.
• Immediately report all severe adverse events (SAE) and submit follow-up reports with subject identifiers to the sponsor and CPHS.

Know and comply with Good Clinical Practice as it relates to this study.

• Maintain a regulatory binder with complete documentation and in compliance with records retention requirements.
• Ensure accuracy, completeness, legibility and timeliness of data reported.
• Ensure data entered in the case report form is consistent with source documents.

Investigator Responsibility Briefing

All UTHSC-H employees who serve as PIs on sponsored projects must complete training on research compliance and regulatory issues (Investigator Responsibility Briefing) as required by UTHSC-H policy (HOOP 23.11 Research Training).  Re-certification through continuing education is required every three years, and courses taken to satisfy the re-certification requirement must be approved by the Executive Vice President for Research. Information and training dates are available on the Office of Research website at: (http://research.uth.tmc.edu/training/InvestigatorResponsibilityBrief.html

Human Subjects Protection Education

UTHSCH policy (HOOP 23.11 Research Training) requires that all investigators participating in research involving human research subjects, human derived materials, or human derived data complete approved training on the protection of human research subjects regardless of the funding source for the research (HRP PP VI.02 Investigator Education).

Training must be approved by the UTHSC-H Human Research Protection Program, and information about the requirement and approved training are available on the Program’s website (http://www.uth.tmc.edu/orsc/training/index.html). 

The training must be completed prior to the approval of protocols by the CPHS, and investigators must provide the Office of Research Support Committees (ORSC) a certificate documenting satisfactory completion of the training.  (fax # 713-500-0319)

Re-certification is also required every three years, and the training program used for certification MUST be approved by the Program. Investigators receive a reminder via e-mail approximately one month prior to the expiration date of their training. For questions regarding the educational requirement, please call the ORSC at 713-500-7942.

Maintenance of Research Study Documents

The principal investigator must maintain study documents for each research project (HRP PP IX.02 Documentation and Record Keeping).  Essential documents for the conduct of clinical trials include appropriate FDA regulatory and human subjects’ research documents. The file must include the following items:

• The original signed protocol, subsequent signed protocols, and signed amendments, and sample case report form
• The investigational brochure(s) with IRB submission memo(s) (if applicable)
• The FDA Statement of Investigator  Form 1572 (if applicable)
• Investigational New Drug (IND)/Investigational Device Exemption (IDE) application, FDA form 1571, and a copy of all correspondence to and from the FDA (if applicable)
• Copy of the Federal grant application (if applicable)
• Curricula vitae with date and signatures, current medical licenses, and financial disclosures for principal investigator and all co-investigators
• Documentation of all CPHS approvals of protocols, consent forms, educational and recruiting materials, advertising, amendments, continuing reviews, protocol deviations, and documentation of all memos to and from the CPHS
• A copy of all recruitment and advertising material
• A copy of all educational or written information given to subjects
• Serious adverse event reports from subjects enrolled locally, all investigator new drug (IND reports) notification reports from the sponsor, and copies of all CPHS approvals, acknowledgements and reports to and from the CPHS
• Copy of IRB approvals from other institutions with collaborating investigators (if applicable)
• Copies of all CPHS and collaborating IRB approved stamped and dated consent forms
• Delegation of responsibilities log with authorized signatures
• Screening and enrollment logs
• Laboratory accreditations, normal lab values, curricula vitae for laboratory director, quality assurance information, and temperature logs (if applicable)
• Investigational products (drug or device), packing lists, inventory records, accountability logs (if applicable)
• A copy of all communication to and from the sponsor including telephone contacts, email, memos, reports and monitor visit documentation (if applicable

Items to file separately:

• All original informed consents that are signed and dated by each subject kept securely.  The investigator is responsible for ensuring that a copy of the signed and dated consent is placed in the subject’s medical record, should the subject be an inpatient.
• Signed clinical trial agreement between institution and sponsor (if applicable)
• Signed confidentiality agreement (if applicable)
• Clinical trial budget and financial agreement (if applicable)

Overview of UTHSCH Process for Reviewing Human Subjects Research

Clinical Trials Registration

National Public Registry
In 2005 The International Committee of Medical Journal Editors (ICMJE) required that certain clinical trials be entered in a public registry (such as ClinicalTrials.gov) before enrolling the first patient, as a condition of consideration for publication. The intent is "to promote the public good by ensuring that everyone can find key information about every clinical trial whose principal aim is to shape medical decision making."

With the Food and Drug Administration Amendments Act of 2007 and enactment of U.S. Public Law 110-85, Title VIII, section 801 on September 27, 2007, Congress expanded the scope of clinical trials that must be registered in ClinicalTrials.gov.

The UTHSC-H is registered as an institution through which our clinical investigators can register their trials at ClinicalTrials.gov.  Responsibility for registering trials lies with the lead sponsor of the clinical study; therefore, most “industry sponsored” trials will be registered by the sponsor, which can be a pharmaceutical company or CRO. Local sponsor-investigator studies (also known as “investigator initiated studies”), or those who hold an IND or IDE that meet the eligibility criteria, will all need to be registered by the investigator prior to study enrollment, where applicable.

The following “applicable clinical trials” that MUST be registered generally include

• Trials of drugs and biologics: Controlled, clinical investigations other than Phase 1 investigations, of a product subject to FDA regulation
• Trials of devices: Controlled trials with health outcomes, other than small feasibility studies, and pediatric post-market surveillance.

Investigators should review the statutory definition of applicable clinical trials to identify if any of their trials must be registered to comply with the law. NIH encourages registration of ALL trials whether required under the law or not, and ICMJE advises that those who are uncertain whether their trial meets the ICMJE definition of eligible trials should err on the side of registering if they wish to seek publication in an ICMJE journal.

The FDA has the authority to enforce compliance with these clinical trial registry requirements. If a sponsor fails to register any trial which meets the eligibility criteria, fails to submit trial results, or submits false data or information, the NIH will post a notice describing the infractions on the registry data bank. The FDA is also authorized to impose monetary penalties for failure to comply with the requirements of the Act. Any person who violates the provisions of the Act will be subject to penalties up to $10,000. After 30 days of notification, uncorrected violations could incur additional $10,000 daily penalties until the violation is corrected.

For more information regarding this requirement, go to: http://prsinfo.clinicaltrials.gov/ or http://www.uth.tmc.edu/research/clinical/ctregistration.htm

Steps for registering clinical trials

• Contact the Protocol Registration System (PRS) Administrator at Catharine.V.Carter@uth.tmc.edu, 713-500-7910 or Gena.Monroe@uth.tmc.edu, 713-500-7903
• Request account setup for PRS users, provide user ID, full user name and email address.
• When notified of account activation (by email), access the PRS website http://register.clinicaltrials.gov.
• Log on and change password.
• Go to Main Menu, Protocol Records, select Create and follow the prompts for Clinical Trials.

UTHSC-H Clinical Trials
The UTHSC-H Clinical Trials website is available for the public to identify clinical research being conducted at UTHSC-H (http://www.uthouston.edu/clinicaltrials/). The website contains listings and descriptions of specific research studies with staff contact information as well as FAQ’s and general information about clinical research.  Investigators may register their clinical trials on our local website.  After registration and prior to posting, the study registration information is reviewed and approved by the CPHS.