Investigator-Initiated Studies

Investigator-Initiated Studies (IIS), also called Investigator-Initiated Trial (IIT), are clinical studies initiated and managed by a non-pharmaceutical company researchers, like individual investigators or institutions. The researcher is responsible for the legal and regulatory responsibilities of the trial sponsor for the conduct and management of the study as defined by all applicable laws and regulations.

Investigators should contact the Director of Clinical Trials for assistance with study development.

Wendy Blount, RN, MSN
Director, USA Health Clinical Trials
(251) 445-9834
wlblount@health.southalabama.edu

Maintaining compliance can be a challenge since these trials are not overseen by a sponsor and monitoring team.  The Office of Research Compliance and Assurance have tools, guidance, practices that can help you at all time-points of your study. For assistance with monitoring of Investigator-Initiated studies please contact:

Stefanie White, CCRP
Associate Director, Research Quality Assurance and Improvement
(251) 460-7573
swhite@southalabama.edu

Below are the steps that you need to take to start-up and manage an IIS trial. Some steps can be done simultaneously, while others need to be done chronologically.

▼   STEP 1: WRITE THE PROTOCOL

Below is a link to a protocol template. It is not required that you use this template. Clinical research protocol templates are widely available on the internet.  E6(R2) Good Clinical Practice: Integrated Addendum[BW3]  outlines the necessary information for a clinical trial protocol and protocol amendments in section 6. It is highly suggested that your compare your finished protocol with section 6 of the above guidance to ensure that all components of the protocol are described. 

Protocol Template

▼   STEP 2: DETERMINE THE FEASIBILITY

It is vital that the logistics and the feasibility be assessed for an IIS. Protocols should be sent to the following individuals to determine the feasibility of an IIS protocol:

Winona (Wendy) Blount, RN, MSN
Director, USA Health Clinical Trials
USA Health Clinical Trials Office
(251) 445-9834 office
wlblount@health.southalabama.edu

Stefanie White, CCRP
Assoc. Director, Research Quality Assurance and Improvement
Office of Research Compliance and Assurance
(251) 460-7573 office
swhite@southalabama.edu

Principal Investigator’s should also start discussing the protocol with departments that they plan to utilize. These departments will also be able to provide feedback on the feasibility of the protocol.

▼   STEP 3: DETERMINE THE BUDGET

This step can be started while the feasibility step is in progress. However, the budget should not be finalized until Step 2 has been completed.

The budget will vary greatly from study to study and will depend on numerous factors. Please contact Wendy Blount for assistance with developing your study budget.

Winona (Wendy) Blount, RN, MSN       
Director, USA Health Clinical Trials         
USA Health Clinical Trials Office            
(251)445-9834 office
wlblount@health.southalabama.edu   

▼   STEP  4: DETERMINE IF AN IND OR IDE IS NEEDED
Investigational New Drug (IND)- The United States Food and Drug Administration's Investigational New Drug program is the means by which a Sponsor (the person who takes responsibility for the study and drug- NOT the funding source) obtains permission to start human clinical trials and to ship an experimental drug across state lines before a marketing application for the drug has been approved.

Please refer to the IND Guide Book for information on conducting a study with an IND.

Investigational Device Exemption (IDE)- allows an investigational device to be used in order to collect safety and effectiveness data required to support a premarket approval (PMA) application or a 510(k) submission to Food and Drug Administration (FDA).

  INVESTIGATIONAL DRUGS - IND INVESTIGATIONAL DEVICES - IDE
FDA REGULATIONS  21 CFR 312 21 CFR 812
GUIDANCE/RESOURCES Investigational New Drug Applications (INDs) - Determining Whether Human Research Studies Can Be Conducted Without an IND (FDA Guidance)
FDA Website
Significant Risk and Nonsignificant Risk Medical Device Studies (FDA Information Sheet; Includes examples of SR and NSR devices)
FDA Website
INITIAL FDA PAPERWORK FOR APPLICATIONS
  1. IND Application: Instructions in 21 CFR 312.22-23
    1. Information for Sponsor-Investigators Submitting Investigational New Drug Applications (INDs) (FDA Guidance)
  2. FDA Form 1571 (IND Application Cover Form): Form ( PDF) | Instructions
  3. FDA Form 1572, Statement from Investigator: Form(PDF) | FAQ - Statement of Investigator (FDA Guidance)
  4. FDA Form 3674, Certificate of Compliance: Form (PDF)
    1. Register the study on ClinicalTrials.gov.
  5. If applicable, a written request for charging the cost of the investigational drug to subjects
  6. Conflicts of interest (financial disclosures) for all participating investigators
    1. Financial Disclosure by Clinical Investigators (FDA Guidance)
The FDA paperwork is not required to be submitted to the IRB. After submission, the FDA will respond within 30 days. All documentation received from the FDA must be kept on file.
  1. IDE Application: Instructions in 21 CFR 812.20
    1. IDE Approval Process( FDA Guidance)
  2. FDA Form 3674, Certificate of Compliance: Form( PDF)
    1. Register the study on ClinicalTrials.gov.
  3. Conflicts of interest (financial disclosures) for all participating investigators
    1. Financial Disclosure by Clinical Investigators (FDA Guidance)

Sponsor-Investigators are encouraged to contact the FDA to obtain further guidance prior to the submission of an IDE application through the Pre-IDE Submission Process.

The FDA paperwork is not required to be submitted to the IRB. After submission, the FDA will respond within 30 days. All documentation received from the FDA must be kept on file.

This step can be done at the same time as STEP 3. It is advised to wait until STEP 2, the feasibility assessment, is complete as it can result in changes to the protocol.

▼   STEP 5: COMPLETE REGULATORY DOCUMENTS
 

The following documents should be created.

  1. Informed Consent Form- Please refer to the Informed Consent page for more information on creating the Informed Consent.
  1. Case Report Forms- The case report form is the tool used by the sponsor of the clinical trial to collect data from each participating patient. The CRFs can be electronic or paper. These forms should collect data points that support the objective(s) of the study, as well as, gather data for subject safety.
  1. Advertisement- Create any advertisements you plan to use for your study. These will need to be approved by the IRB
▼   STEP 6: SUBMIT TO THE IRB AND OTHER REGULATORY BOARDS
 

Institutional Review Board

All research involving human subject must be approved by the Institutional Review Board BEFORE you enroll any subjects or gather any data. Any IIS research must go through the University of South Alabama IRB; it cannot go through WIRB.

For more information on how to submit to the IRB, please review the Getting Started section of the Research Compliance and Assurance’s webpage.

Institutional Biosafety Committee

Please review the Getting Started section of the Biosafety webpage to see if your study requires IBC approval.

Data Safety Monitoring Board

A Data and Safety Monitoring Board (DSMB) is an independent group of experts that advises the sponsor and the study investigators. The members of the DSMB serve in an individual capacity and provide their expertise and recommendations. The DSMB evaluates research data on an ongoing basis to assure participant safety and study integrity. The DSMB periodically reviews study data and unanticipated problems and makes recommendations based on their reviews along with assessing the performance of overall study operations and any other relevant issues, as necessary. The following is a list criterion for the use of a DSMB:

  • Multi-site clinical trials with interventions that entail risk(s) to participants
  • If the trial is evaluating mortality or another major endpoint, such that inferiority of one treatment arm has safety as well as effectiveness implications.
  • Any research done in an emergency setting where the informed consent requirement is waived.
  • All phase III clinical trials with the exception of behavioral and nutritional studies
  • Phase I or II trials that involve blinding
  • The trial includes vulnerable population and is greater than minimal risk
  • When it would be ethically important for the trial to stop early if the primary question addressed has been definitively answered, even if secondary questions or complete safety information were not yet fully addressed.
  • When there is prior information suggesting the possibility of serious toxicity with the study treatment
  • Studies that do not meet the above criteria, but are required by the funding source to be reviewed by a DSMB.

If you have any questions about using a DSMB or if you need assistance determining if your study requires a DSMB, please contact:

Stefanie White, CCRP
Associate Director, Research Quality Assurance and Improvement
Office of Research Compliance and Assurance
swhite@southalabama.edu
Ph: (251) 460-7573

▼   STEP 7: REPORT ON CLINICALTRIALS.GOV
 

More information to come. Please contact Stefanie White for more information.

Stefanie White, CCRP Associate Director, Research Quality Assurance and Improvement
Office of Research Compliance and Assurance
swhite@southalabama.edu
Ph: (251) 460-7573