"Conducting Clinical Trials A-Z"

STUDY INITIATION: 4 ADMISSION TICKETS TO INITIATE


A CLINICAL TRIAL AT UK:

The following processes to initiate a trial should be started concurrently as each will require some preparation, routing, negotiation, review and approval.  If you require assistance or guidance on competing the study initiation, contact the UKCRO initiation or education unit.

Initiation Process Flow Chart (PDF)

FEDERAL/ REGULATORY DOCUMENTS

These are standard documents required for all FDA regulated trials along with any additional documents or requirements set forth in the sponsor’s SOPs (may require originals for both site and sponsor).  Rapid turn-around of these documents is critical and will place your site in high standing with sponsor. 

These documents will be the foundation for the Study Regulatory Binder. 

Typically you will receive a complete initiation package with instructions on the requirements for handling each document. Original copies are usually sent to the sponsor and either originals or copies will be maintained in the site binder (some sponsors require original signed documents be held at both sponsor and site).

Initial documents may include:

• Instructions for completing and submitting documents (includes contacts and usually provides express mail account for sending documents to sponsor.

• Protocol, Protocol Amendments, and Investigator Signature Page Sign signature page to affirm your review of the protocol and commitment to adhere to the protocol when conducting trial.  Do Not Sign if includes any contractual language, and forward to the Clinical Trials Administrator. 

• Investigator’s Brochure – monograph on all pre-clinical and clinical research data on an investigational drug (for your information and to include with the IRB submission).

• Clinical Trial Agreement (Draft Contract – deliver to Michael Brown, Clinical Trials Administrator, Office of Sponsored Projects Administration) to email michael.brown2@uky.edu

• Sponsor financial disclosure statements

• Sample or template forms (preferably electronic) such as informed consent or FDA Form 1572

In addition to the above completed forms you will need to send the sponsor:

• All investigator CVs - show current position with UK, signed & dated within last 2 years

• Medical license

• DEA license (if applicable)

• IRB member list

• Some sponsors collect a copy of the institution’s Federal Wide Assurance (FWA) held with the Department of Health & Human Services or an IRB Statement of Compliance with 21 CFR. (contact UKCRO or ORI for copies)

• Lab certification (CAP & CLIA) & lab normals if using the UK lab for any part of the trial including PRN safety labs.

• Draft Informed Consent Form – sponsor will likely review prior to submission to IRB

• Completed FDA Form 1572 (Statement of Investigator)

• Signed protocol signature page and financial disclosures

• IRB review, revisions, & final approval letter itemizing what was reviewed/approved and stamped approved consent form. 

Practical Tips when completing the FDA Form 1572

• Use current form - expires 2006

• No white-out or illegible entries

• PI name and address should be the same as on CV

• List all research site locations

• List research labs - local and/or central lab for multi-site trial

• IRB name & address

• Signed by the PI

• Include as sub-investigators those individuals who are directly (not indirectly) involved in the treatment and evaluation of the patient/subject. Such individuals, for example, would be qualified to diagnose disease, prescribe medications, and make medical decisions on behalf of the patient in the context of the protocol (e.g. assess adverse event causality, discontinue the patient, adjust dosage(s) of concomitant medications, determine the clinical significance of an observed change from baseline, interpret important safety or efficacy data).

• Modify if change in PI or key personnel

• Include attachments as described above – CVs for PI and sub-investigators listed on 1572; IRB membership lists, and if using the UK lab include certifications and normal values for all lab tests listed in the protocol.

  FINANCIAL/ BUDGET DEVELOPMENT

Before committing to conduct a trial, carefully and accurately cost out all expected and anticipated expenses. The UKCRO can provide this service for you or refer to the UKCRO fiscal management guide to get you started.  

  CLINICAL TRIALS AGREEMENT (CTA) is a contract or legal agreement between the university and sponsor outlining terms of research obligations, rights, and financial matters. (template agreements are available on the OSPA website)

As soon as you receive a template CTA from sponsor forward to clinical trial administrator along with:

• Contact at sponsor, or CRO acting on behalf of the sponsor, responsible for negotiation (include phone, fax, e-mail)

• Phase of Study

• State if approved drug is being used for an unapproved use

• Study protocol

NOTE: any budget information attached to the contract must be negotiated by the PI or UKCRO on behalf of the PI and should be finalized prior to completion of the contract. OSPA negotiates the terms of the contract only and will not negotiate the budget or compensation.

Once the terms of the CTA are approved, the following internal documents must be provided to the Clinical Trials Administrator in order to execute the CTA (OSPA forms website):

• Completed and signed Internal Approval Form

• Fixed-Price Budget Sheet, Column A completed

• University of Kentucky Disclosure of Financial Interest Forms

• IRB approval letter if available

TIP: Provide your sponsor with following helpful information:

1. contact for contract negotiation (Clinical Trials Administrator),

2. designated signature for institution - Deborah Davis, Director of OSPA, Assistant Director, UKRF

3. designation of where checks are made payable to (University of Kentucky Research Foundation UKRF which is a non-profit, affiliated corporation of the University of Kentucky through which grants and contracts from external sponsors are received)

4. Employer Tax Identification Number 61-6033693

5. your (PI) name and address where payment is sent.

  IRB SUBMISSION –

The Office of Research Integrity (ORI) provides support for six federally mandated review committees, three Medical and a Nonmedical Institutional Review Board (IRB), the Institutional Animal Care and Use Committee (IACUC), and the Radioactive Drug Research Committee (RDRC). Copies of application forms, information on policies and procedures, and UK's Statements of Assurance can be obtained from ORI.

Federal and state regulations require that the use of human subjects in research be reviewed and approved by an IRB.  The UK IRB consists of three medical boards who will meet six times per month.  

Typically clinical trials are not exempt from IRB review.  Most clinical trials with medical interventions will require full IRB board review.   CLICK HERE for the IRB, Full, Expedited, and Exempt Application Forms.

TIP: Put information (dates or version numbers) on the footer to identify and differentiate versions at stages of review.  Sponsors will generally want to pre-view the draft consent form, HIPAA forms and any advertising prior to your submission to the IRB. 

You will receive a scheduled meeting for IRB review of the:

• Protocol – list version (3 copies)

• Protocol amendments (3 copies)

• Investigator brochure or package insert for marketed drugs (monographs available on Micromedex. (3 copies)

• Submission packet including research description and general information sheet (GIS), and signature assurance sheet (18 copies collated).  You will need to estimate the targeted/planned enrollment of the following members of minority groups and their subpopulations.  Demographic websites may help:

http://quickfacts.census.gov/qfd/states/21000.html
http://www.louisville.edu/~easchn01/kentucky/demos1.html
http://censtats.census.gov/data/KY/04021.pdf
http://www.uky.edu/Home/AnnualReport/

• Informed consent form (use both sponsor’s and UK IRB templates to produce a blended form and have sponsor review prior to submission; see informed consent process guidance below)

• Health Insurance Portability and Accountability Act (HIIPAA) authorization form (HIPAA templates are available on ORI website)

• Recruitment materials (flyers, posters, newspaper, radio and television ads, public service announcements, dear-doctor letters, Web announcements).  Upon request, UKCRO will develop and obtain approval from Public Relations on print advertising.

• other written (educational) material or study questionnaires

The investigator, sometimes accompanied by the coordinator, will attend the IRB review and answer questions for the review board About a week after the IRB meeting, you will receive correspondence with any requested modifications and pending revisions, you will receive an IRB approval letter and stamped informed consent form, (send copies to the sponsor and retain originals in your regulatory binder). Note: Approval will be withheld until all key personnel listed on the General Information Form have completed Human Subject Protection Training.

The ORI Website provides guidance on ongoing IRB communications such as adverse events, continuation review, protocol modifications, etc.

Additional Tickets (Applications) if applicable:

Radiation safety – for protocol calls for procedures more significant or frequent than normal standard care or at unapproved facilities (radioactive materials, radio frequencies, x-rays for research and/or clinical care, lasers (non-ionizing), microwaves, or infrared rays).   Contact Andy Miller (859) 323-6308), Radiation Safety Officer, in advance for suggested language for consent forms, (equivalents, etc).  Additional descriptions may be found at the Radiation Info website.

Biosafety committee – required for protocols using infectious agents, rDNA, Human gene therapy, or vaccines. See website for application process and templates

Environmental Health and Safety Requirements Checklist for Research Grants and Contracts

Radioactive drug committee – reviews basic pharmacology of new radioactive materials.

General Clinical Research Center – to request GCRC services (administration, core lab services, data safety and analysis, patient care and database management).

Clinical Care and Research Teams (CCART) The Markey Cancer Center (MCC) requires that any Medical Center cancer-related clinical research be reviewed and approved by the MCC Protocol Review and Monitoring System (PRMS) (Coordinate through the MCC Research Coordinating Center, 859-323-1671).

VA R & D submission – required for trials conducted at VAMC facilities or using VAMC resources or patients.