Investigator Initiated Studies (IITs)

Investigator Initiated Trials (IITs) or Studies(IIs) are clinical studies initiated and managed by Penn Medicine/ PSOM investigators. In these cases, the PI may be serving as a sponsor – investigator; means an individual who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed (21 CFR 312.3). The term does not include any person other than an individual. If an academic investigator submits an IND or IDE or obtains an abbreviated IDE from the IRB and is the principal investigator, the investigator is the Sponsor-Investigator and he/she is responsible for regulatory compliance. Academic investigators sometimes equate the term “Sponsor” with the source of the study funding. In fact, there are two types of sponsors: regulatory sponsor and financial sponsor. The regulatory sponsor is the person/entity who initiates and takes responsibility for a clinical investigation. The regulatory sponsor submits the IND or IDE when applicable and is responsible for communications with the FDA.  

The Sponsor Investigator is responsible for all of the following. Resources on these items can be found in various other sections of clinical trial execution.  

  1. Protocol Development  
  2. ClinicalTrials.gov posting  
  3. Regulatory requirements for clinical trials  
  4. Drug trials 
  5. Device Trials  
  6. Vendor qualification and management  
  7. Pharmacovigilance (PV) 
  8. Investigational Product Management and Accountability  
  9. Maintenance of the Trial Master File (TMF)  
  10. Trial Document management (protocol, consent, etc.) 
  11. Data Management and Database development  
  12. Monitoring  
  13. Product Development and Preclinical Research; as applicable   

A: The Office of Clinical Research's (OCR) Regulatory Service is designed to help with all your FDA drug and device regulatory questions. Their goal is to assist faculty in their pursuit of medical innovation and discovery while fulfilling all aspects of research ethics and compliance.   

A: Federal law requires that FDA-regulated products be the subject of an approved marketing application before transported or distributed across state lines. The Investigational New Drug (IND) Application [21 CFR 312] or the Investigational Device Exemption (IDE) application [21 CFR 812] is the mechanism to conduct human research with an FDA regulated product.  

A: Drugs that are not approved for any indication would be considered new drugs. However, approved drugs may be considered “new” in the context of a clinical trial if the trial changes how the drug is used when compared to the approved label, such as:  

  • New route of administration  

  • New dose or duration of exposure  

  • New form of the drug (e.g., capsule vs. tablet)  

  • New treatment indications (e.g., target disease, age, gender)  

  • New use with concomitant meds  

 

A: Yes, an IND exemption can be granted by the FDA, CAMRIS (for radiology products) or the Office of Clinical Research's (OCR) Regulatory service. For OCR use the IND Exemption Request Form to submit to an IND exemption request to the OCR. The FDA has six criteria for determining if the use of a drug or biologic in a research investigation meets the qualifications for exemption from FDA IND regulation [21 CFR 312.2(b)]. The criteria are:  

  • The investigational drug is lawfully marketed in the United States.  

  • The investigation is not intended to be reported to the FDA as a well-controlled study in support of a new indication for use of the drug product.  

  • The investigation is not intended to support a significant change in advertising to an existing lawfully marketed prescription drug product.  

  • The investigation does not involve a route of administration or dosage level or use in a patient population or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product.  

  • The investigation will continue to be conducted in compliance with the requirements for institutional review set forth in FDA regulations 21 CFR 56, and requirements for informed consent as set forth in FDA regulations 21 CFR 50.  

  • The investigation will continue to be conducted in compliance with FDA regulations 21 CFR 312.7: i.e., the drug may not be represented as safe or effective, nor may it be commercially distributed, for the purposes for which it is under investigation.  

A: Device studies fall under three different categorizations: investigations exempt from IDE regulations, investigations subject to abbreviated requirements (Abbreviated IDE or Non-Significant Risk (NSR) devices), and investigations subject to full requirements (full IDE or Significant Risk (SR) Devices). The Sponsor is responsible for making an initial risk determination. The risk determination is based on the proposed use of a device in a study and not on the device alone. A thorough discussion of how to make significant vs. non-significant risk determinations for devices is available from the FDA guidance on medical device studies.  

A: An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is:  

  • recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them,  

  • intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or  

  • intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and  

which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes.

A: The Study Sponsor.  The entity (person, company, or institution) who submits and maintains an IND or IDE application with the FDA or other health authority is called the Regulatory Sponsor or IND, IDE, or CTA Holder. The Regulatory Sponsor holds overall responsibility for the application  and for all activities conducted under the application . All FDA regulated research must be conducted in compliance with federal regulations,  21 CFR 312 for Drugs and 21 CFR 812 for Devices. Contact the Office of Clinical Research's (OCR) Regulatory Services regarding registration, qualification and training of Faculty IND, IDE, and CTA sponsors.   

A: There are options for how to submit to the FDA based on the type of application and the entity to which you are submitting.  OCR Regulatory has submission resources and guidance available upon request.  

A:  The responsibility for investigational product(s) accountability at the trial site(s) rests with the investigator/institution. The investigator/institution should assign some or all of the investigator’s/institution’s duties for investigational product(s) accountability at the trial site(s) to an appropriate pharmacist or another appropriate individual who is under the supervision of the investigator/institution.  The Investigational Drug Service (IDS) can provide these services.  

A: The Investigational Drug service can help with the management of devices. There are five areas of device management.  

  • Account ability logs  

  • Storage  

  • Dispensing  

  • Reconciling inventory  

  • Destruction  

A: The accountability log is a standardized tool for documenting exactly what happens to an investigational product during the course of a study. The log documents the receipt, the dispensation, use, transfers to other study sites, and the return or destruction of the product. Products are inventoried by the lot and/or serial number and quantity. The Office of Clinical Research provides a sample Investigational Product Subject Log.  

A: The Investigational Drug service can help with device storage. Store according to the manufacturer specifications and limit access to the investigational devices only to authorized personnel. For significant risk devices used in surgery, the Operating Room (OR) has two main storage areas separate from non-research device storage: 1) the Radiofrequency Cabinet and 2) the Stent Closet.  

A: The Investigational Drug service can help with device dispensing. For devices maintained by the HUP operating room (OR), the OR may be delegated by a Principal Investigator to maintain copies of shipping records, order forms, packing slips and return documentation in study-specific master files for a specified period, after which records are transferred to the research team. The Principal Investigator is responsible for documentation regarding implantation and use of devices as required by the study protocol, federal regulations, and institutional policy. These responsibilities may be delegated to other research team members, as appropriately trained and qualified.  

A: The Investigational Drug service can help with device reconciliation. For industry-sponsored studies, the sponsor will determine the disposition of the remaining inventory of the study devices. The sponsor may request that the unused product be returned or destroyed. In either case, it is important for the research staff to document the following information:  

  • Identifying information (lot, batch, or serial numbers)  

  • Quantity of device used and unused  

  • Shipping information (for returned devices)  

  • Means of device destruction and person responsible for destruction  

  • Date of device destruction  

A: The Investigational Drug service can help with device destruction. The destruction of devices must be tightly controlled with detailed record-keeping to capture study-specific information which will not be retrievable once the products are destroyed, as well as to assure that there is no loss or theft of the product.  

A: ClinicalTrials.gov is both a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world maintained by the National Library of Medicine (NLM) at the National Institutes of Health (NIH). It is a resource for patients and researchers to identify clinical studies conducted on various diseases and health conditions.  

A: If you are the Sponsor or the Sponsor-investigator of the study, then yes. Registration and results reporting of clinical trials is required by law. Any interventional clinical trial using a drug, biologic or device that fits the definition of Applicable Clinical Trial (ACT) must be registered and results submitted in the ClinicalTrials.gov website in accordance with Title VIII of the Food and Drug Amendments Act of 2007, known as FDAAA 801.  Here is a checklist for evaluating whether your study fits the ACT definition. In addition, Dissemination of NIH-Funded Clinical Trial Information mandates registration and results reporting for clinical trials funded in whole or in part by NIH, even if they are not ACTs. This checklist can be used to determine if your human subjects research study meets the NIH definition of a clinical trial.  

A: Penn researchers who plan to publish their clinical trial (even if it does not meet the criteria of an ACT or NIH funding) must provide an NCT # at the time of submission.  The requirements from the International Committee of Medical Journal Editors (ICMJE) state that clinical trials must be published on a public trial registry as a condition for publication at or before the time of the first subject enrolled.  

A: Registration of your clinical trial should be submitted prior to enrollment of the first subject. It is recommended that it is done in parallel with your IRB submission.  If the study is under an IND or IDE you will be required to include attestation of Clinical Trials.gov requirement with the initial application or with each new protocol submission.   

A: Penn researchers should complete the following steps  

  • Complete the ClinicalTrial.gov training in Workday Learning  

  • Complete a request for a PRS account in REDCAP.  Within 1-2 business days, a PRS administrator will create the account and email login access.  

  • Click here to access ClinicalTrials.gov Protocol Registration and Results System (PRS)  

  • The organization code on the login page is “UPenn”  

  • Click on “New Record” on the opening page to begin a new study registration  

  • Assign necessary staff to maintain the record through completion via access list  

  • When editing your record, you may leave the record status to “In Progress” until you have finalized the update.  Your record is always saving.  

  • Your record is complete and ready for the next step when all PRS comments and system errors are addressed.  Be sure to click “complete” and the local PRS administrator or responsible party will be notified to review and release the record for the central PRS review. If the record is satisfactory, it will be entered on the public website ClinicalTrials.gov.  

A: Update the Protocol Section and Submit  

  • Ensure that the information in the Protocol Section is up-to-date before starting the Results Section (for example, the Overall Recruitment Status, Study Start Date, Primary and Study Completion Dates, Actual Enrollment, and arm and intervention information).  

  • Begin results submission after the updated record has been made public on ClinicalTrials.gov.  

     Enter the required and optional results data elements  

  • Applicable clinical trials with a primary completion date on or after January 18, 2017 are required to submit a copy of the protocol and statistical analysis plan (if not included in the protocol) per 42 CFR 11.48(a)(5).  The responsible party may redact names, addresses, and other personally identifiable information, as well as any trade secrets and/or confidential commercial information.  The submission format should follow the common electronic document format specified at https://prsinfoclinicaltrials.gov  

  • For basic help with using PRS, review the Quick Start Guide also found in the Help section of the PRS main menu.  

  • See the results data preparation checklists and simple results templates for each module, listed in the Scientific Information, for the data you will need and a view of the data elements in a tabular format.  

  • See the Helpful Hints (PDF) for tips on entering results data, including three examples of common study models (parallel design, crossover design, and diagnostic accuracy studies) and measure types.  

  • Note, personnel that will be submitting results information are strongly encouraged to have a statistical background, or to submit results information alongside personnel with statistical background (e.g. a statistician or a physician/ scientist). Guidance is available for results reporting from OCR Compliance or the ACC Data and Safety Monitoring Committee (for cancer relevant trials).