CTA Submittal

Clinical Trial Agreement Submittal Process

A clinical trial agreement is the contract between an industry sponsor and University outlining the obligations of each party for the conduct of a sponsor-authored protocol that involves human subjects and the testing of a drug or medical device. 

The following steps outline the most efficient process for initiating a private industry supported clinical trial for testing biomedical drugs or devices in accordance with FDA regulations. This process enables OCTA to negotiate a clinical trial agreement while the Principal Investigator secures other campus and compliance committee approvals.

While submitting an industry sponsored clinical trial for review, EPD must be used by all departments. The following paperwork must also be uploaded to EPD before a contract can be signed:

• Draft Contract from Sponsor (if available);
• Draft Budget;
• Protocol
• Complete Proposal Application (contract, budget and protocol combined as a PDF)

IRB number is required prior to OCTA's approval in EPD.

All paperwork must be submitted in order for the OCTA Contract Officer to begin contract negotiations.

CTA Tips and Preparatory Services

Contact Information

In addition to the Principal Investigator's contact information, it is important to provide complete contact information of the sponsor or CRO, if applicable, representative, especially a phone number and/or email address. The more information the OCTA Contract Officer has, the faster and more efficiently the sponsor or CRO may be contacted in order to begin the contract negotiations.

Location of the Study

If the study will be conducted at more than one location, each location must be listed. If the locations change after the contract negotiation begins, inform the contracts negotiator as soon as possible. If this information is not accurate, it will delay the execution of the contract and may subject the University to unknown risks and liability.

Signatures

The Clinical Trial Agreement Request form or EPD system must be signed by the Principal Investigator, Department Chair, and Department Business Officer before ​the informed consent may be released by OCTA to HRPP. Incomplete forms will delay the start of the study.

700-U Form (PI's Statement of Economic Interest)

Instructions on how to complete this form and to download it from the web, can be found at http://coi.ucsd.edu. California law requires University faculty members to disclose whether or not they have a financial interest in outside entities that sponsor research. This disclosure is made using the 700-U form. If there is a positive disclosure, i.e. the faculty member has an economic interest in the sponsor, the conflict of interest must be reviewed and approved by the UCSD Conflict of Interest (COI) Committee. This approval process is monitored by your contracts negotiator and no action on your part is required. Keep in mind that the COI only meets once a month. No agreement can be signed until the COI approval is obtained.

Budget

• A budget must be submitted showing all anticipated costs of the clinical trial and the overhead rate of 30%. 
• Costs that should be included are: Total Direct costs, (i.e. patient care costs, special procedures, supplies and expenses, pharmacy fees, IRB review fees, etc.,) as well as indirect costs. 
• There is a separate mandatory IRB fees for the IRB review and ongoing monitoring of the project. There fees are invoiced to the sponsor with the initial review, with the annual review and the four-year renewal.
• For more information about budget preparation submit a service request.

IRB Approval Letter

A contract cannot be finalized and a study cannot begin until there is IRB approval. The application process for IRB approval should be submitted simultaneously with the OCTA submittal process. IRB approval and final contracts will not be released until both are approved for signature.

For more information on the Institutional Review Board (IRB) and the submission process, visit the UCSD Office of IRB Administration.

CTA Actions (Role of OCTA)

Pre-Award Process

The OCTA Contract Officer will:

• Contact the sponsor to initiate contract negotiations;
• Provide the sponsor with the standard UCSD agreement if a sponsor agreement is not provided;
• Obtain a copy of previous agreement (if applicable);
• Review and propose revisions to the contract;
• Negotiate final revisions to the contract;
• Forward the final agreement to the Principal Investigator for signature (the PI will then send the signed contract back to the OCTA contract Officer );
• Sign the Agreement on the behalf of The Regents;
• Forward the signed contract to the Sponsor (the Sponsor will then sign the signed contract back to the contract negotiator). 

Once the appropriate paperwork has been submitted, please check the OCTA Dashboard for the in-process status and notes about the study.

Contract Negotiations

Negotiations involving a contract can sometimes be quite complex and lengthy, depending upon the sponsoring organization and the nature of the work to be performed.

Contracts with clinical trial sponsors (e.g., pharmaceuticals or medical device companies, clinical research organizations) cover human testing activities related to an investigational drug, compound or device leading to approval by the Food and Drug Administration for commercial distribution.

As a public, nonprofit educational institution, the University is bound by certain policies and regulations regarding what it can and cannot accept in a clinical trial contract. These policies are designed to protect the welfare of individuals participating as research subjects; foster the University's basic mission of teaching, research and public service; and minimize the various forms of liability associated with human subject research.

For-profit private sponsors, such as pharmaceutical companies, are motivated by different forces than the University. As a result, they sometimes do not understand the ideals and principals behind our policies. Consequently, additional time may be required for contract negotiations while the contracts negotiator works with the sponsor to arrive at a mutually acceptable agreement.

When negotiating clinical trial contracts, the University primarily focuses on securing acceptable contract clauses regarding high-risk issues such as subject injury, indemnification, confidentiality, ownership of data, patent rights and publication rights.

The University's standard clinical trial agreement and the clauses proposed by the University during contract negotiations are based on the following assumptions:

• That the clinical investigation is conducted under a protocol that is a FDA Phase I, II, III, or IV drug study or a FDA regulated medical device study.
• That the Sponsor provides its proprietary product and study protocol to the University for the purpose of conducting a clinical trial; and
• That the sponsor will fully fund the cost of the trial (i.e., no work will be supported in whole or in part with other fund, including Federal funds).

Post-Award Process

• The index number will be assigned within 1 business day
• Distribution of a copy of the executed agreement to the Principal Investigator and study team will be included with the index number

Contract Amendments

Amendments, modifications, and Addenda should be entered into the OCTA Application: http://som.ucsd.edu/OCTAApplication 

CTA Actions (Role of PI)

Closing a Clinical Trial

Upon the closure or termination of a clinical trial, there are certain steps that must be taken in order to complete the closing process. The following departments need to be notified of the study closure:

• The IRB should be notified in a written format that the trial is being closed, the date and the reason for the closure. Include the number of participants enrolled (if any), the number of withdrawals and the number of adverse events. HRPP will then update their records accordingly.
• OCTA must be copied on one of the above notifications so that the OCTA can update the contract records at octa@ucsd.edu.
• Conflict of Interest should be notified by completing the 700-U and marking in section 2 that this is a complete statement. The updated 700-U should be sent to Conflict of Interest at mail code 0992.

Staying abreast of the financial status of the clinical trial is always important but it is even more important when it's time to close the study. This includes ensuring the sponsor has provided payment for all the work performed, reconciliation of institutional accounts, etc.

Registration for Clinical Research Trials

Interventional studies with health outcomes must be registered, and may be required to report results, in ClinicalTrials.gov. This requirement applies to:

1. All NIH-funded trials, including phase 1 studies and clinical trials of behavioral or non-FDA-regulated interventions (Registration and Results required).
2. Clinical trials involving FDA-regulated drug, biologic and device products (Registration and Results required).
3. Studies that will bill routine costs to Medicare or any other insurer (Registration required).
4. Any study intended for publication in a journal recognized by the ICMJE (Registration required).

Those responsible for conducting a clinical trial must make sure that they are in compliance with the trial registration requirements of the Food and Drug Administration (FDA), the National Institutes of Health (NIH), the International Committee of Medical Journal Editors (ICMJE), and as required by other organizations with policies on clinical trial registration for transparency and publication.

Section 801 of the Food and Drug Amendments Act, known as FDAAA 801, requires registration of studies meeting the definition of “Applicable Clinical Trial” on a government web site called ClinicalTrials.gov.

The US National Institutes of Health (NIH) final policy of 2016 established the expectation that all investigators conducting clinical trials funded in whole or in part by the NIH will ensure that these trials are registered and results information is submitted to ClinicalTrials.gov. Compliance with FDAAA is a legal requirement and a term and condition of the NIH award. All competing applications (new and renewal) and progress reports for NIH grants (including cooperative agreements) supporting clinical trials must include a certification of compliance with FDAAA.

The International Committee of Medical Journal Editors (ICMJE) requires, and recommends that all medical journal editors require, as a condition of consideration for publication, registration of [all] clinical trials in a public trials registry at or before the time of first patient enrollment.

Effective January 1, 2015, Center for Medicare and Medicaid Services (CMS) will require a clinical trial identifier (NCT#) be reported on all billing claims for items/ services related to a qualifying clinical trial(s). If your study will bill routine costs to Medicare or any other insurer, the study must be registered on ClinicalTrials.gov to obtain the NCT#.

Please see the

• UCSD RCI Requirements for Registering Clinical Trials
• UCSD Factsheet Decision Tree for Registering Clincal Trials
• UCLA Example Resource: Registering in the ClinicalTrials.gov Registry - Guidance for UCLA Sponsor-Investigators
• UCLA Example Resource: UCLA Creating a New Study Record - Tips on how to initiate a new record
• UCLA Example Resource: Resolving Problem Records - This guide explains the types of problem and how to resolve
• Summary of HHS/NIH Initiatives to Enhance Availability of Clinical Trial Information (effective January 18, 2017)
• Clinical Trial Registration for NIH Grantees Frequently Asked Questions (FAQs)
• Certifying compliance in NIH Grants and Progress Reports
• Changes from Current Practice Described in the Final Rule (PDF) (December 2016)

If you have questions or need assistance, please contact Project Management and Support for Clinical Trials.

Definition of a Clinical Trial

The World Health Organization (WHO) defines a clinical trial as “any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes. Interventions include but are not restricted to drugs, cells and other biological products, surgical procedures, radiological procedures, devices, behavioral treatments, process-of-care changes, preventive care, etc.”

The U.S. National Institutes of Health (NIH) defines a clinical trial as: "A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.” 

Consistent with the definition developed by the WHO, the International Committee of Medical Journal Editors (ICMJE) defines a clinical trial as “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.”

The FDA defines an Applicable Clinical Trial (ACT) as follows:

• Trials of drugs and biologics: controlled clinical investigations, other than Phase 1 investigations, of a product subject to FDA regulation.

• Trials of biomedical devices: 1) controlled trials with health outcomes of devices subject to FDA regulation, other than small feasibility studies, and 2) pediatric post-market surveillance.

For complete statutory definitions and more information on the meaning of Applicable Clinical Trial, see Elaboration of Definitions of Responsible Party and Applicable Clinical Trial (PDF).

If you have questions or need assistance, please contact Project Management and Support for Clinical Trials.

Why Register My Study?

According to the World Health Organization (WHO), “The registration of all interventional trials is a scientific, ethical and moral responsibility.”

According to the World Medical Association (WMA) Declaration of Helsinki (2013): it is stated that “Every research study involving human subjects must be registered in a publicly accessible database before recruitment of the first subject.” and that “Researchers have a duty to make publicly available the results of their research .... Negative and inconclusive as well as positive results must be published or otherwise made publicly available”.  

Registration may be required by law and/or policy if any one (or more) of the following is true:

If you have questions or need assistance, please contact Project Management & Support for Clinical Trials.

How to Register a Study

Refer to the UCSD Blink section on Clinical Trials Registration.

Qualifying Clinical Trials

The National Coverage Decision (NCD) offers specific guidance concerning Clinical Trials Billing.

Under the National Coverage Decision (NCD), Medicare will cover those routine costs of qualifying clinical trials and the costs of items and services that are reasonable and necessary* to diagnose and treat complications arising from participation in all clinical trials (Centers for Medicare and Medicaid Publication 100-3, Ch 1, Part 4, Section 310.1).

Learn more about Qualifying Clinical Trials for Devices.

If you have questions or need assistance, please contact ACTRI's Clinical Trial Support Services (CTSS) for Clinical Trials.

Applicable Clinical Trials FAQ

Definition of a Clinical Trial

The World Health Organization (WHO) defines a clinical trial as “any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes. Interventions include but are not restricted to drugs, cells and other biological products, surgical procedures, radiological procedures, devices, behavioural treatments, process-of-care changes, preventive care, etc.”

The U.S. National Institutes of Health (NIH) defines a clinical trial as: “A research study  in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.”

Consistent with the definition developed by the WHO, The International Committee of Medical Journal Editors (ICMJE) defines a clinical trial as “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, behavioural 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.”

The FDA defines an Applicable Clinical Trial (ACT) as follows:

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

For complete statutory definitions and more information on the meaning of Applicable Clinical Trial, see Elaboration of Definitions of Responsible Party and Applicable Clinical Trial (PDF).

What is a Qualifying Trial

Under the National Coverage Decision (NCD), Medicare will cover those routine costs of qualifying clinical trials and the costs of items and services that are reasonable and necessary to diagnose and treat complications arising from participation in all clinical trials (Centers for Medicare and Medicaid Publication 100-3, Ch 1, Part 4, Section 310.1).

The trial may be “Qualifying” if it:

• Is funded/supported by NIH, CDC, AHRQ, CMS, DOD or VA
• Is supported by centers or cooperative groups that are funded by the NIH, CDC, AHRQ, CMS, DOD and VA
• Has an IND number
• Is conducted under an IND/IDE reviewed by the FDA
• Is exempt from having an IND/IDE
• Is conducted an abbreviated IDE

-OR-

Your trial (All three criteria must be "Yes"):

• Evaluates a Medicare benefit
• Has therapeutic intent
• Enrolls diagnosed beneficiaries

For additional information regarding “Qualifying Trials” please refer to Qualifying Clinical Trials on ResearchGO.

Do I need to register my “Qualifying Trial” even if it is not an “Applicable Clinical Trial” under FDAAA?

Yes, your trial must be registered in ClinicalTrials.gov if it is a “qualifying trial” even if it doesn’t meet the definition of an “Applicable Clinical Trial.” According to a recent CMS mandate, a clinical trial number must be reported on claims for items and services provided in clinical trials that are qualified for coverage as specified in the “Medicare National Coverage Determination (NCD) Manual, “ Section 310.1.

The clinical trials number to be reported is the number assigned by the National Library of Medicine (NLM) http://clinicaltrials.gov website (an 8-digit # preceded by “NCT”, a.k.a. “the NCT #”) when a study appears in the NLM Clinical Trials database.

When must my ‘Qualifying Trial” be registered in ClinicalTrials.gov?

Your “Qualifying Trial” must be registered in ClinicalTrials.gov prior to IRB approval

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. This penalty has not changed over time.

According to the FDA/NIH (Food and Drug Amendments Act of 2007):

Penalties may include civil monetary penalties up to $10,000 fine for failing to submit or for submitting fraudulent information to ClinicalTrials.gov. After notification of noncompliance, the fine may go up to $10,000 per day until resolved. For federally funded grants, penalties may include the withholding or recovery of grant funds.

What is an applicable clinical trial according to the Food and Drug Administration Amendments Act (FDAAA) Section 801?

Applicable Clinical Trial (ACT) is the term used in Title VIII of the Food and Drug Administration Amendments Act of 2007 (FDAAA) (PL 110-85) to designate the scope of trials that may be subject to the registration and reporting requirements in FDAAA. FDAAA defines the term using two other terms defined in the Act, namely an “applicable drug clinical trial” or an “applicable device clinical trial.”

Detailed definitions can be found in the Elaboration of Definitions of Responsible Party and Applicable Clinical Trials document.

In general, a study is likely subject to the requirements of FDAAA if YES is answered to all five questions below:

1. Was the study initiated after September 27, 2007 (OR ongoing as of December 26, 2007)?
2. Is the study ‘interventional’ (i.e., participants are assigned to interventions by protocol)?
3. Does the study intervention include a ‘drug’, ‘biological product’, or ‘medical device’ (whether or not approved for marketing in the United States)?
4. Is the study not considered a phase I clinical investigation (e.g., a phase 2 study) OR not considered a ‘small feasibility’ device trial (e.g., a pivotal study)?
5. Does the study have at least one site located in the United States OR is the study conducted under an IND or IDE?

Are investigator-initiated trials applicable clinical trials?

Yes, investigator-initiated trials are applicable clinical trials if they meet the criteria outlined above.

Can non-randomized trials be considered ACTs?

Yes – non-randomized trials can be “Applicable Clinical Trials” if they meet the other criteria. In non-randomized trials, participants are expressly assigned to intervention groups through a non-random method, such as physician choice. Keep in mind, a single –arm study often uses a historical comparison. See below for details regarding ‘controlled’ studies.

What does ‘controlled’ mean when it comes to deciding if a study is an ACT or not?

A study where a control is not expressly outlined in the protocol may still be considered an applicable clinical trial if it meets the other criteria outlined above. A controlled clinical investigation is one that is designed to permit a comparison of a test intervention with a control to provide a quantitative assessment of the drug effect. The purpose of the control is to distinguish the effect of a drug from other influences. The control provides data about what happens to human subjects who have not received the test intervention or who have received a different intervention. Generally, the types of control that are used in clinical investigations are (1) placebo concurrent control; (2) dose-comparison control; (3) no intervention concurrent control; (4) active intervention concurrent control; and (5) historical control.

What clinical trials are specifically excluded from the definition applicable clinical trials according to FDAAA?

• Phase 0 and phase I drug trials (however, these trials may still require registration per FDAMA Section 113).

• Small feasibility device trials and larger clinical trials of prototype devices with a primary measure of feasibility rather than health outcomes.

• Trials that include only de-identified human specimens and do not include human subjects.

Additional information can be found in the Elaboration of Definitions of Responsible Party and Applicable Clinical Trials document.

Who is responsible for registering protocols and reporting results for applicable clinical trials?

The “Responsible Party” is the entity or individual responsible for meeting FDAAA requirements for registering protocols and reporting results of ACTs. The responsible party is generally either the regulatory sponsor or the principal investigator. Note that the regulatory sponsor and financial sponsor are sometimes the same entity (i.e., a pharmaceutical company).

Generally speaking, the regulatory sponsor of an ACT will register and report the results of the trial if they:

• Are the company/organization that initiates the trial (multicenter or otherwise) and its employees conduct the trial;
• Are an individual who initiates a trial, but has someone else conduct the investigation;
• Hold the IND or IDE.

Generally speaking, Principal Investigators of applicable clinical trials will register and report the results of the trial if:

• The obligation is delegated to the principal investigator by the regulatory sponsor;
• The principal investigator is responsible for conducting the trial, analyzing the data, has rights to publish results and has the ability to meet all of FDAAA’s requirements for the submission of clinical trial information.

If there is more than one award supporting a non-IND/IDE ACT, who is the Responsible Party?

Investigators and institutional officials associated with the trial should work together to determine the Responsible Party and ensure that the other grantees are aware of the designation.

If you have questions or need assistance, please contact ACTRI's Clinical Trial Support Services (CTSS) for Clinical Trials.

General Clinical Trial FAQs

My study is not yet IRB approved. Can I enter it on ClinicalTrials.gov?

Yes, you can! ClinicalTrials.gov will allow registration of the study prior to getting IRB approval if the Overall Recruitment Status of the study is “Not yet recruiting.” IRB approval must be obtained before the study’s Overall Recruitment Status is changed to “Recruiting”. When IRB approval is obtained, update the protocol registration and release the study to ClinicalTrials.gov for review and processing.

Can I register a study after it has started, has closed to recruitment, or has completed?

Yes, you can register a study on ClinicalTrials.gov at any time. However, FDAAA Section 801 requires applicable clinical trials to be registered within 21 days of enrollment of the first participant. ICMJE journals (and other journals) require registration of all clinical trials before enrollment of the first participant.

As of January 18, 2017, the NIH requires registration and results reporting for all NIH supported clinical trials, regardless of whether or not they are required to do so under FDAAA. Results submission for non-applicable clinical trials is not required (for example, a behavioral study) by FDAAA 801

If no participants were ever enrolled in the trial, no results must be reported. Remember to change the Overall Recruitment Status to “Withdrawn.”

For a trial that terminated early after participants were enrolled, provide any available data for Participant Flow, Baseline Characteristics, Outcome Measures, and Adverse Events. If no data are available for any of the Outcome Measures, specify zero (“0”) for the Number of Participants Analyzed in each Arm/Group, and leave the data fields blank. Provide an explanation in the Analysis Population Description for why zero participants were analyzed and, if appropriate, provide information in the Limitations and Caveats module. You must still provide data for Participant Flow, Baseline Characteristics, and Adverse Events.

The data must be reported on ClinicalTrials.gov as soon as possible. The International Committee of Medical Journal Editors has indicated that they do not consider publishing to ClinicalTrials.gov as “pre-publication.” Here’s a link to their FAQs that may be useful. 

One can ask for an extension/delay in disclosing results by contacting the ClinicalTrials.gov staff (register@clinicaltrials.gov), but the request would need to meet their definition of “good cause” and publication issues are generally excluded from that definition.

Communication with the journal regarding the legal obligatory requirements may also be useful. It’s unlikely that the journal would refuse a manuscript when the institution/investigator is mandated by law to disclose publicly. However, if the trial was not registered according to the ICMJE journal requirements (prior to enrollment of first participant), the journal may take issue with that and reject the manuscript on that basis.

The new NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information is complementary to the statutory and regulatory reporting requirements of FDAAA and establishes the expectation that all investigators conducting clinical trials funded in whole or in part by the NIH will ensure that these trials are registered and results information is submitted to ClinicalTrials.gov. See more FAQs for NIH Grantees.

Because data reviews are retrospective and largely observational in nature and, in general, exempt research studies are not controlled clinical trials, nor involving an FDA-regulated intervention, they would not need to be registered or reported on ClinicalTrials.gov.

However, the ICJME may have a different opinion if exempt research involves any of the following:

• Drugs:
• surgical procedures;
• devices;
• behavioral treatments;
• dietary interventions;
• process-of-care change.
• biomedical or health-related measures including pharmacokinetic measures and adverse events.

If the applicable clinical trial has reached the primary completion date, then results must be submitted by the Responsible Party no later than 12 months after the primary completion date. If the ACT is investigating mortality over a long period of time (e.g., 10 years) and the investigator chooses to analyze mortality trends over time during the course of the study, the outcome measures may be revised in the PRS according to the desired analysis timeframe while the study is still ongoing. If, in this example, the only primary outcome measure is mortality at 10 years and the investigator does not choose to analyze the data prior to the primary completion date, the study will still be considered ongoing. The record, however, should be updated regularly to accommodate for enrollment status and protocol/amendment verification.

The primary outcome measure should have an estimated time frame.
Many times studies include a mortality endpoint and could remain open for several years following the completion of the intervention under investigation. Should we wait until study is closed to enter results?

If the applicable clinical trial has reached the primary completion date, then results must be submitted by the Responsible Party no later than 12 months after the primary completion date. If the ACT is investigating mortality over a long period of time (e.g., 10 years) and the investigator chooses to analyze mortality trends over time during the course of the study, the outcome measures may be revised in the PRS according to the desired analysis timeframe while the study is still ongoing. If, in this example, the only primary outcome measure is mortality at 10 years and the investigator does not choose to analyze the data prior to the primary completion date, the study will still be considered ongoing. The record, however, should be updated regularly to accommodate for enrollment status and protocol/amendment verification.

Yes, but you may ‘delay results posting’ until 30 days after the product receives FDA approval or clearance. You do not qualify for this delay if you are using approved products ‘off-label’. Only investigational products (i.e., no FDA approvals/clearance for any indication) qualify for delayed results posting. However, the NIH requires results reporting for all NIH supported clinical trials registered in ClinicalTrials.gov, regardless of whether or not they are required to do so under FDAAA.

FDAAA requires the reporting of results for all pre-specified primary and secondary outcome measures/endpoints for applicable clinical trials. Tertiary and exploratory outcomes are not captured as part of FDAAA.

Though there is no official guidance, ClinicalTrials.gov generally advises completing data entry ASAP but not later than 12 months after data collection has ended for that measure. If data collection is ongoing, it is a good idea to provide the anticipated posting date for that measure so it is clear to the public when the information will be made available.

In a case like this, the study team may submit an extension request, indicating that the study has not been unblinded and reporting the primary outcome measure data would interfere with the scientific integrity of the study.

For studies that do not involve a drug or biologic, such as behavioral interventional studies or device trials, select ‘Not Applicable’.

FDAAA does not require that patient-level data/raw data be entered into ClinicalTrials.gov. Summary data, similar to that represented in manuscripts, is entered into ClinicalTrials.gov

The ClinicalTrials.gov protocol registration/results reporting system interface was originally developed prior to 2000 when ‘results reporting’ was not a requirement. Since the implementation of the ICMJE requirements and FDAAA enactment, this system has been adapted in many ways to meet challenging data requirements. Continuous enhancement occurs as various users make suggestions to the ClinicalTrials.gov staff. It is likely, however, that the tool will continue to maintain a form/function similar to the current tool.

Trials that were “ongoing” as of December 26, 2007 (i.e., participants were being recruited, were being selected from a predetermined population, or were being treated or examined) require results reporting within one year of the Primary Completion Date. The Primary Completion Date is defined as the date the final subject was examined or received an intervention for the purposes of final collection of data for the primary outcome, whether the clinical trial concluded according to the pre-specified protocol or was terminated.

Related Guidance, Tools and Templates

Additional Tools & Guidance

• Resolving Problem Records
• Outcome Measures Guidance
• Registration and Results Reporting Time Estimates (OMB Burden Statement)

Results Reporting Tools

• Common Errors
• Pre-Submission Checklist
• Results Examples
• How to Submit Results
• Submitting Results Webinar-May 14, 2013
• Sample Results Template (single-arm study)
• Sample Results Template (2-arm study)
• Sample Results Template (3-arm study)
• Checklists, templates, and examples to help gather information needed to report results to ClinicalTrials.gov

Related Links

• 2016 Final Rule for FDAAA 801 (effective January 18, 2017)
• 2016 NIH Policy on the Dissemination of NIH-funded Clinical Trial Information
• NIH-Funded Clinical Trials and FDAAA FAQs
• Summary information on FDAAA 801 (U.S. Public Law 110-85) requirements
• FDA guidance for Bioresearch Monitoring (BIMO)
• U.S. Public Law 110-85 - FDA Amendments Act of 2007
• ICMJE FAQs
• ClinicalTrials.gov Protocol Data Element Definitions
• ClinicalTrials.gov Results Data Element Definitions

If you have questions or need assistance, please contact 

Inspections

FDA & OHRP Inspections

For routine inspections expect to receive an FDA pre-announced inspection phone call from one to three days in advance of the visit.  Please notify the Health Sciences Office of Compliance and Privacy upon receiving the call or letter from the FDA to schedule the inspection.

The following general guidelines are recommended during an FDA inspection from the time the FDA inspector is greeted to the time the exit interview is conducted and a response to the FDA’s observations are made. 

• Investigators are required to permit the FDA to inspect and copy any records pertaining to the investigation including, in certain situations, those which identify subjects
• Designate a person to serve as escort who will oversee the inspection (usually the research coordinator for the study) 
• The escort serves as an institutional monitor as well as guide and general study contact person
• The FDA inspector must not be permitted free access to areas where files are kept

Please contact Health Sciences Office of Compliance and Privacy and the IRB for important information and guidance on Inspections and Audits.

Before the Site Inspection

Before the Site Inspection

• Complete the FDA Site Pre-Inspection Checklist and identify records the FDA is likely to audit.
• Identify all subjects, enrollment/screening log, and ALL Informed Consents.
• Selected Case Report Forms and all supportive source documentation.
• Sequester these records and your reviews in readiness for easy access, but do not volunteer a list of them to the inspector. Always wait for a specific request to provide information.
• If necessary, schedule a room for your inspection.
• One week prior to Inspection, the coordinator should review the Coordinator Checklist.

Inspector Arrival

Please also refer to your department policy for FDA site inspections.

• There may be times when persons at other institutions (e.g., department directors) should be notified that the FDA is conducting an inspection in the building.
• Where a sign in log is used: if the inspector will not sign in, make a note in the sign in log of the name, date/time, purpose and escort name. 
• The escort will walk the inspector to an appropriate meeting room. The inspector will present his/her credentials to verify that they are in order; do not expect the investigator to permit a copy to be made of the badge/credentials. 
• The inspector will then present a Notice of Inspection (Form 482) to the Principal Investigator, this notice authorizes the inspection and its presentation officially begins the inspection. 
• The inspector will explain the intended purpose and scope of the inspection, then ask the PI to summarize the study.

The Inspection

The FDA or OHRP Inspection

The escort should have made arrangements for a comfortable work area for the FDA inspector(s) for the duration of the inspection. The room must contain no confidential records, including clinical or research related. The inspector should be accompanied by the escort or designee at all times while in the presence of study related documents, samples, or other confidential information. If the inspector needs to make a phone call and requires some privacy, they should have access to a “sterile” room (no study related information is present) or public area where they can conduct their business. In general, while an inspector is here in an official capacity, they should not be left alone.

The inspector must never have access to any site records not specifically provided by the host. Standard procedure is for the inspector to request files for review, starting with the “general” study materials including the regulatory documents binders, then all signed informed consent forms, followed by a sampling of specific patient records. Study finances and personnel records are not included in the standard inspection.  The Principal Investigator should set aside time each day to talk with the inspector, as well as being available for questions that may arise.

The escort’s role is to coordinate all FDA requests and see that the inspector’s questions are answered honestly and completely. Listen to the question; answer the question that was asked. Defer to others if you don't know; when possible use documents already provided for support of answers. Stop when the question is fully answered. There is nothing wrong with silence: when you have answered, wait for the next questions. 

How to answer FDA Questions:

• Be concise; answer only the question that is asked
• Always be clear with the answers to questions
• Be positive and confident
• Take corrective actions if possible, commit only to what you can deliver
• DO NOT volunteer information.
• DO NOT guess or speculate
• DO NOT lie
• DO NOT argue
• DO NOT panic
• DO NOT sign affidavits

Please see the UCSD guidance on Preparing for an FDA Clinical Investigator Inspection for additional information.

Inspection of Documents

• Escort the inspector to an information sterile room away from sources of casual conversation to review requested documents.  Always sequester the reviewer in an isolated room and bring the requested documents to them.
• Only documents specifically requested by the inspector shall be provided for review. The escort may need to obtain patient records from the hospital or clinic records to supplement or corroborate the research records.
• Gather the documents requested for review. When documents are copied for inspectors, a copy is also made to retain or identify each copied document by maintaining an inspection record log. All copies provided should be stamped “Confidential”. Usually copies are provided without charge to the FDA; however, if the inspector requests an inordinate number of copies, notify the inspector that an invoice will be provided.
• Documents that the inspector is not entitled to review or copy: financial, personnel (except for training/qualification records), and internal audits (section 704(a) FDC Act).

Photographs

If the FDA inspector insists on taking photographs, take duplicates at the same time.

Samples

If the FDA inspector requests a reasonable quantity of samples, fill the request but pull identical samples to retain. Ask the FDA to issue a receipt for the samples (FDA Form 484). Depending on the nature of samples requested, advise the FDA that an invoice will be presented.

After the Inspection

The Exit Interview

The FDA will usually hold an exit interview at the conclusion of the inspection. The escort, Principal Investigator, a representative from Institutional Compliance, and other individuals as appropriate should be notified of the time and place and expect to attend. During this exchange, if serious deficiencies have been found during the inspection, an Inspectional Observations (FDA Form 483) will follow from the regional office, listing the deficiencies. If no deficiencies are found, or the inspector has comments that she or he believes are not serious enough to warrant an FDA Form 483, no form will be issued.

During the exit interview:

The Principal Investigator will seek to correct any errors in the findings. Both the FDA and Principal Investigator will make sure everything is clear and understood. Observations, comments, and commitments will be noted in the escort inspection notes.

After the Inspection

Responding to FDA Form 483:
The PI or designated representative shall draft a response to an FDA Form 483. The PI is responsible for sending the draft of the response to the institutional contacts listed below. The PI is also responsible for sending the written response to the FDA for review and comments prior to sending the final response to the FDA. The PI is responsible for sending the draft of the response to the institutional contacts listed below.

The written response should include specifics:

• Determine if a finding was an oversight/one-time occurrence; or systemic, where a change of procedure is indicated.
• Delineate corrective actions: including justification of why the proposed response will remediate the issue; and a realistic timeline for correction.
• If the PI disagrees with an observation: respond factually, providing clear and verifiable evidence.
• Address each particular observation or finding, point by point.
• The reply should be sent within 15 business days. Keep a copy of the final signed response in your office.

To Request an Establishment Inspection Report (EIR)

The FDA inspector will file an EIR within approximately 30 days. This report is subsequently available through the FOI. It may be requested from:

FOI, Freedom of Information Office
5600 Fisher
Rockville, MD  20857

Institutional Followup

Please provide a copy of the final establishment inspection report (EIR) and/or the Inspectional Observation Form 483 upon receipt to the IRB (IRB@ucsd.edu) & Research Compliance & Integrity (RCI@ucsd.edu)

FDA Alerts

See the following links for alerts, announcements, and safety recalls from the U.S. Food and Drug Administration.

MedWatch Safety Alerts for Human Medical Products

MedWatch alerts provide timely new safety information on human drugs, medical devices, vaccines and other biologics, dietary supplements, and cosmetics.

FDA Drug Information
Index of FDA Approved Drugs

FDA Index to Specific Drug Information This Index does not include all FDA approved drugs. It only includes drugs that have been the subject of a Drug Safety Communication, Healthcare Professional Information sheet, Early Communication About an Ongoing Safety Review, or other important information. Please use Drugs@FDA to search for information on a drug not found in the Index.

Recalls, Market Withdrawals, & Safety Alerts
List of recalls, alerts, and warnings of foods, drugs, medical devices, and cosmetics.

FDA Drug Alerts and Statements
Information on drug safety and availability for consumers and health professionals, new drug warnings and other safety information, drug label changes, and shortages of medically necessary drug products.

Dietary Supplement Alerts and Safety Information Alerts
FDA alerts for consumers and healthcare professionals.

FDA Drug Alerts – Cancer
FDA notification of recent FDA approvals and other important FDA actions pertaining to therapies for cancer patients.

FDA Device Alerts
Problems with medical devices may be caused when devices malfunction.  But problems also may arise when users--either health professionals or the general public--do not understand or follow proper use instructions. FDA issues alerts and warnings to explain why problems may be occurring and clarify proper procedures to ensure safe and effective use of devices.

Postmarket Drug Safety Information for Patients and Providers
Links to safety sheets with the latest risk information about particular drugs, related press announcements, and other fact sheets.

Related Guidance, Tools & Templates

General Guidance for Site Inspections
Customizable template that outlines the process for an FDA/OHRP inspection, and describes activities that should be done to facilitate the inspection

FDA Site Pre-Inspection Checklist and Coordinator Checklist
Organizational tools to aid inspection preparation

FDA Inspection Information
Intake form for FDA/OHRP Inspection Requests

Preparing for an FDA Inspection General information for Coordinators to prepare for and participate in external audits and what comprises inpection readiness

For more information, contact the Research Compliance & Integrity office.

Budgeting Services

Refer to Clinical Trials Blink regarding Budget information.

For assistance with budgeting your research trial, request services through the ACTRI's Clinical Trial Support Services (CTSS). 

Business Contracting

The Office of Business Contracting services and assists faculty and departments to collaborate with outside entities to advance the UC mission of education and community services.  Business Contracting negotiates the following:

Clinical Service Agreements (CSA)

• UC provides a service for a fee
• Physician providing patient care.
  • i.e. Cardiologist seeing patients at a community clinic for an hourly rate
• Before submitting a request for a CSA, confirm that the physician does not have a conflict with the outside practice, hospital, or nonprofit organization. If there is a conflict, the 700-U forms must be submitted for clearance from the Conflict of Interest Office.

Training (formerly Affiliation) Agreements

• An inter-institutional agreement which provides for the training of undergraduate medical and pharmacy students and/or graduate medical and pharmacy students (residents and fellows) at hospitals and clinics and which meets the requirements of UCOP and accrediting organizations (ACGME, LCME, ASHP, ACPE).

State/Local Government Agreements

• Contracts or Agreements with State of California agencies and with local government agencies (ie. County of San Diego).  These agencies have “caps” or limits on indirect costs.  This agreement type is only used with State of California or local government agencies with such caps.

Provider Agreements

• Agreements covering SOM purchase of services from outside providers that involve patient services (professional services, facility use).  These transactions are rare and are distinguished from basic purchase orders issues by the purchasing department because they involve highly regulated medical group functions.

Consulting Agreements with outside Organizations

• Professional agreements with outside organizations. 
• Agreements can be for a flat fee or an hourly rate.
• Examples include faculty consulting by sitting on steering committees, attending conferences and  providing feedback on study procedures.
• Required forms and documents to accompany submission:  700-U form.

Laboratory Service Agreements (LSA)

• Pre-Clinical activities involving non-human clinical observations.
• Here, the UC acts merely as a pair of hands to perform a service.
• Examples of laboratory services include performing assays, reading scans or analyzing data and testing propriety substances in controlled settings.
• UC provides deliverables to the outside organization often in the form of routine statistical data.
• Does not contemplate or negotiate intellectual property rights or assignments.
• Required forms and document to accompany submission: 700-U form, Laboratory Service Questionnaire and Scope of Work.

Required forms such as the 700-U and Laboratory Services Questionnaire can be found here.

Contact

The Office of Clinical Trials Administration (OCTA) has the responsibility and authority to negotiate and execute agreements that meet the above definition of a clinical trial when (i) under an industry developed protocol and (ii) funded by industry. Such industry sponsor-initiated and funded clinical trials are authored and funded by a pharmaceutical, device, biotech company, or for-profit Clinical Research Organization (CRO) whether directly or indirectly through another academic medical center or non-profit organization.The Office of Contract and Grant Administration (OCGA) has the responsibility and authority to negotiate and execute a broader spectrum of research agreements, including UCSD Investigator authored clinical trial protocols and clinical trials funded by the government or a non-profit entity.

Effective August 1, 2016, the OCTA Clinical Trial Agreement Request Form will no longer be used.  All Health Science departments have been onboarded to ePD. Clinical trials must be submitted to ePD.

Training and Approval Access is required for the proposal creators in order to create a new Clinical Trial proposal in ePD. 

For questions, please contact OCTA@ucsd.edu or 858-822-2940.

Support: For more detailed information or to discuss how the ACTRI Clinical Trial Support Services can assist you, please contact us at actri-ctss@health.ucsd.edu. 

Roles and Responsibilities

Office of Clinical Trials Administration (OCTA)

Glossary

Payment Methods

For information regarding payments, see OCTA Financial or e-mail OCTAFinancials@ucsd.edu.

CTA Actions (Role of OCTA)

Pre-Award Process

The OCTA Contract Officer will:

• Contact the sponsor to initiate contract negotiations;
• Provide the sponsor with the standard UCSD agreement if a sponsor agreement is not provided;
• Obtain a copy of previous agreement (if applicable);
• Review and propose revisions to the contract;
• Negotiate final revisions to the contract;
• Forward the final agreement to the Principal Investigator for signature (the PI will then send the signed contract back to the OCTA contract Officer );
• Sign the Agreement on the behalf of The Regents;
• Forward the signed contract to the Sponsor (the Sponsor will then sign the signed contract back to the contract negotiator). 

Contact Information

​​​​​The OCTA team is working remotely with access to email and voicemail. The preferred method to reach us is by email. If you call, please leave a voicemail. This will trigger an email alert to the OCTA staff member you are trying to reach. For urgent matters, please also email octa@health.ucsd.edu and include “URGENT” in the subject line.

Mailing Address:

UC San Diego, ACTRI
Attn: Office of Clinical Trials Administration
9500 Gilman Drive, Mail Code 0990
La Jolla, CA 92093-0990

Contact:

Email: octa@health.ucsd.edu
Phone: 858-822-2940 (leave a message)

OCTA Staff

Once the appropriate paperwork has been submitted, please check the OCTA Dashboard for the in-process status and notes about the study.

Contract Negotiations

Negotiations involving a contract can sometimes be quite complex and lengthy, depending upon the sponsoring organization and the nature of the work to be performed.

Contracts with clinical trial sponsors (e.g., pharmaceuticals or medical device companies, clinical research organizations) cover human testing activities related to an investigational drug, compound or device leading to approval by the Food and Drug Administration for commercial distribution.

As a public, nonprofit educational institution, the University is bound by certain policies and regulations regarding what it can and cannot accept in a clinical trial contract. These policies are designed to protect the welfare of individuals participating as research subjects; foster the University's basic mission of teaching, research and public service; and minimize the various forms of liability associated with human subject research.

For-profit private sponsors, such as pharmaceutical companies, are motivated by different forces than the University. As a result, they sometimes do not understand the ideals and principals behind our policies. Consequently, additional time may be required for contract negotiations while the contracts negotiator works with the sponsor to arrive at a mutually acceptable agreement.

When negotiating clinical trial contracts, the University primarily focuses on securing acceptable contract clauses regarding high-risk issues such as subject injury, indemnification, confidentiality, ownership of data, patent rights and publication rights.

The University's standard clinical trial agreement and the clauses proposed by the University during contract negotiations are based on the following assumptions:

• That the clinical investigation is conducted under a protocol that is a FDA Phase I, II, III, or IV drug study or a FDA regulated medical device study.
• That the Sponsor provides its proprietary product and study protocol to the University for the purpose of conducting a clinical trial; and
• That the sponsor will fully fund the cost of the trial (i.e., no work will be supported in whole or in part with other fund, including Federal funds).

Post-Award Process

• The index number will be assigned within 1 business day
• Distribution of a copy of the executed agreement to the Principal Investigator and study team will be included with the index number

Contract Amendments

Amendments, modifications, and Addenda should be entered into the OCTA Application: http://som.ucsd.edu/OCTAApplication 

OCTA Index Creation

Once a study has received IRB approval and has a fully executed CTA, the OCTA financial team will set up your index. This process usually takes place within 24 business hours of contract execution (if the study is IRB approved). This study-specific index is where you will be able to manage your study related expenses in accordance with UC policy. The generated index will be linked to the research account (formerly "Bulk Account") for each study. We recommend completing the research account application when submitting to the IRB and completing the CTA form.  For assistance completing the Research Account application please contact ctri-velos@ucsd.edu.

If you are member of a study team and your role requires you to be notified of the index setup, please send us an email to OCTAFinancials@ucsd.edu with your contact information and study details, and we will be happy to add you to the notifications list.

CDA | NDA Overview

Confidential Disclosure Agreements (CDA) or Non-Disclosure Agreement (NDA)

The first step in initiating a clinical trial is obtaining the protocol from the sponsor or the Contract Research Organization (CRO). Usually before the sponsor or the CRO is willing to release a copy of the confidential protocol, they will require that a Confidential Disclosure Agreement (CDA) be signed. The CDA should be signed by a University representative on behalf of its employee, the potential investigator. Note that the OCTA only handles NDAs for sponsor-initiated trials.

As soon as the potential investigator receives the CDA, it should be entered into the OCTA Application, http://som.ucsd.edu/OCTAApplication along with the contact information for the sponsor or CRO. The OCTA analyst will then review the CDA to ensure the terms and conditions of the document are in compliance with University policies. Should revisions be necessary, the OCTA analyst will contact the sponsor or CRO to negotiate language acceptable to both parties. To ensure any unnecessary delay in getting the protocol to the potential investigator, the initial sponsor or CRO contact, the CDA review will occur within 24-72 hours of the OCTA receiving the CDA.

Problem areas with CDA's may include:

• Sponsor Ownership of Intellectual Property arising out of the trial;
• Potential investigator indemnifies sponsor for breach of confidentiality;
• Governing law is a state other than California;
• No end date to the CDA;
• Publication restrictions

After the CDA is signed and the potential investigator receives the protocol, s/he will determine the feasibility of conducting the clinical trial at UC San Diego.

Some of the issues that should be considered are:

• Does the investigator have the necessary patient population;
• Is the protocol well designed;
• Are the study timelines reasonable;
• Does the investigator's staff have the time to take on another study.

Once the decision is made to conduct the clinical trial, the investigator should start the IRB submission and (in parallel) submit the appropriate paperwork to OCTA. Please be prepared to provide OCTA with the IRB number.

SPO | Sponsored Projects Office

Learn about the Office of Contract and Grant Administration at UC San Diego.