Disclosure Requirements for ClinicalTrials.gov: Your FAQs Answered (Part 1)

Barbara Godlew
President, The FAIRE Company, LLC
November 6th, 2012

Disclaimer: This information is intended to provide an overview of the current state of clinical trial registration and results disclosure. Regulatory requirements are paraphrased for clearer communication. Sponsors/institutions should consult their Legal, Regulatory Affairs, and/or Clinical Trials Office departments for institutional practice and policy.*

Barbara Godlew, President of The FAIRE Company, LLC, answers the questions received from attendees of the webinar “Disclosure Requirements for ClinicalTrials.gov: What Institutions Need to Know.” This is the first part in a two-part series of FAQs related to clinical trial disclosure requirements for ClinicalTrials.gov.

Q:  If an academic institution is managing records completed by individual investigators, should the Responsible Party be the PI or S-I?  In the past, the institution’s administrators marked the university as the responsible party.

A: Some institutions function in the manner you describe (ie, University as Responsible Party) regarding who retains responsibility for registering the trial and reporting the results and it seems to work well in some cases. However, if your institution is conducting a large number of trials, this method may be overwhelming to the person managing notifications from ClinicalTrials.gov about individual clinical trials.

Q:  Are data reviews or exempt research excluded from reporting?

A:  FDAAA defines applicable clinical trials as Phase II-IV controlled interventional studies (with one or more arms) of drugs, biological products, or devices that are subject to FDA regulation, meaning that the trial has one or more sites in the United States, involves a drug, biologic, or device that is manufactured in the United States (or its territories), or is conducted under an investigational new drug application (IND) or investigational device exemption (IDE)… If the clinical trial is not of a drug or device subject to FDA regulation, and, thus, not an applicable clinical trial, it is not required to be registered or reported on ClinicalTrials.gov. My understanding is that data reviews and most exempt research are not controlled clinical trials involving an FDA-regulated intervention and would not be need to be registered or reported on ClinicalTrials.gov. FDAAA, however, does not prevent investigators from voluntarily reporting data from clinical trials that do not meet the definition of an applicable clinical trial. For additional clarification, please contact contact ClinicalTrials.gov at register@clinicaltrials.gov or Jarilyn Dupont (jarilyn.dupont@fda.hhs.gov) at the FDA.

QIf there is difficulty for investigators or staff in entering certain types of data/information into ClincalTrials.gov, would you recommend them registering with a different registry? (Citing the ICMJE article that ClinicalTrials.gov is NOT the only registry)

A:  Although the ICMJE allows registration in other registries, FDAAA does not. Applicable clinical trials must be registered and reported on ClinicalTrials.gov. For additional information about these trials, please see the Elaboration of Responsible Party and Applicable Clinical Trials document at http://prsinfo.clinicaltrials.gov/ElaborationsOnDefinitions.pdf 

Q:  Can you confirm what is considered study start date?

A: ClinicalTrials.gov considers “study start date” to be the date that enrollment to the protocol begins.

Q:  Would a phase I study of an IND drug with a limited phase II MTD expansion require results to be reported?

A:  Yes. If the study is considered Phase I/II, the “II” portion takes precedence and must be registered if it meets the other requirements of being an applicable clinical trial.

Q:  Is an observational study that is collecting data on patients who may or may not have taken an investigational product considered to be a clinical trial? The sponsor I am working with claims this would qualify as a clinical trial but I don’t agree. Please advise.

A:  Observational studies are not currently required to be registered/reported on ClinicalTrials.gov by FDAAA. The ICMJE may have a different opinion because subjects are receiving interventions.

Q:  At our academic institution, we register most clinical research projects whether they are ACTs or not.  So, if I understand you correctly, results are not required for those trials that are not ACTs.  How do we make that distinction in the posting so that it doesn’t appear that the posting is incomplete (missing results)?

A:  ClinicalTrials.gov does not make a public distinction between what is/is not an ACT. Internally, at your institution, you should consider employing or developing a tracking/compliance method to ensure that you are posting results to applicable clinical trials in the time frame required.

Q:  If a study is prematurely closed (for any number of reasons) and an analysis is not done, how should we record that in ClinicalTrials.gov?  Does it matter if there are no subjects enrolled, vs. some subjects enrolled?

A:  Trials that terminate prematurely must still indicate that the trial is closed via the “Enrollment Status” field and a brief explanation of why the study was terminated should be provided. If you collected data during the trial and the trial meets the definition of an applicable clinical trial, results must be reported on ClinicalTrials.gov. A good example of this is NCT00004500, which was terminated early.

Q:  As you are aware, many times oncology studies include a mortality endpoint. Therefore, many trials remain open for several years following the completion of the intervention under investigation. Should we wait until study is closed to enter results?  We have received conflicting advice from clinicaltrials.gov.

A:  If the applicable clinical trial has reached the primary completion date (ie, completed data collection for the primary endpoint/outcome measure) whatever the timeframe, results of must be submitted by the Responsible Party no later than 12 months after the primary completion date. If the applicable clinical trial is investigating mortality over a long period of time (eg, 10 years) and the investigator chooses to analyze mortality trends over time during the course of the study, the outcome measures may be revised 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.

Q:  Would the use of a non-significant device used as an intervention outside it’s approved treatment vs. standard of care considered ACT?

A:  Unfortunately, I do not have a background in the determination of significant risk/non-signifcant risk devices, but according to language from the Elaborations of Responsible Party and Applicable Clinical Trial document:

“…a non‐significant risk device considered to have an approved IDE in accordance with 21 CFR § 812.2(b)… would be an applicable device trial if it meets the other qualifications of applicable device trial.”

Please see the following for more information:

Information Sheet Guidance For IRBs, Clinical Investigators, and Sponsors. Frequently Asked Questions About Medical Devices. http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf

Information Sheet Guidance For IRBs, Clinical Investigators, and Sponsors. Significant Risk and Nonsignificant Risk Medical Device Studies. http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126418.pdf

Alternatively, you can visit: http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/default.htm for information on contacting a specific department within FDA with your question.

 

If you are interested in learning more about solutions for disclosure requirements, register for the upcoming webinar “Solutions for Compliance with ClinicalTrials.gov Disclosure Requirements

 

*Disclaimer: This presentation is the intellectual property of Barbara Godlew owner of The FAIRE Company, LLC and protected under the copyright laws of the United States of America and other countries. Use by permission. All rights reserved.

This information is intended to provide an overview of the current state of clinical trial registration and results disclosure. Regulatory requirements are paraphrased for clearer communication.

Sponsors/institutions should consult their Legal, Regulatory Affairs, and/or Clinical Trials Office departments for institutional practice and policy.

2 Comments

2 thoughts on “Disclosure Requirements for ClinicalTrials.gov: Your FAQs Answered (Part 1)

  1. Hi,
    I do have some comments on these FAQs. Thanks for letting me through in my 2 cents. April

    QUESTION: If an academic institution is managing records completed by individual investigators, should the Responsible Party be the PI or S-I? In the past, the institution’s administrators marked the university as the responsible party.

    ANSWER: Some institutions function in the manner you describe (ie, University as Responsible Party) regarding who retains responsibility for registering the trial and reporting the results and it seems to work well in some cases. However, if your institution is conducting a large number of trials, this method may be overwhelming to the person managing notifications from ClinicalTrials.gov about individual clinical trials.

    C.Please elaborate with IND studies. IND holders are the responsible party so therefore the RP should be indicated as S-I.

    Q: Is an observational study that is collecting data on patients who may or may not have taken an investigational product considered to be a clinical trial? The sponsor I am working with claims this would qualify as a clinical trial but I don’t agree. Please advise.

    A: Observational studies are not currently required to be registered/reported on ClinicalTrials.gov by FDAAA. The ICMJE may have a different opinion because subjects are receiving interventions.

    C:What is ICMJE’s opinion?

    Q: At our academic institution, we register most clinical research projects whether they are ACTs or not. So, if I understand you correctly, results are not required for those trials that are not ACTs. How do we make that distinction in the posting so that it doesn’t appear that the posting is incomplete (missing results)?

    A: ClinicalTrials.gov does not make a public distinction between what is/is not an ACT. Internally, at your institution, you should consider employing or developing a tracking/compliance method to ensure that you are posting results to applicable clinical trials in the time frame required.

    C: ClinicalTrials.gov will notify you if the study needs results. Check the “problems” list. Unfortunately there is not public reference to what is required to post results.

    Q: If a study is prematurely closed (for any number of reasons) and an analysis is not done, how should we record that in ClinicalTrials.gov? Does it matter if there are no subjects enrolled, vs. some subjects enrolled?

    A: Trials that terminate prematurely must still indicate that the trial is closed via the “Enrollment Status” field and a brief explanation of why the study was terminated should be provided. If you collected data during the trial and the trial meets the definition of an applicable clinical trial, results must be reported on ClinicalTrials.gov. A good example of this is NCT00004500, which was terminated early.

    C: Studies that terminate early because of no accrual should indicate the status as “withdrawn” and therefore no results will need to be posted. Other reasons for termination with accrual will still need results posted.

    1. “QUESTION: If an academic institution is managing records completed by individual investigators, should the Responsible Party be the PI or S-I? In the past, the institution’s administrators marked the university as the responsible party.
      ANSWER: Some institutions function in the manner you describe (ie, University as Responsible Party) regarding who retains responsibility for registering the trial and reporting the results and it seems to work well in some cases. However, if your institution is conducting a large number of trials, this method may be overwhelming to the person managing notifications from ClinicalTrials.gov about individual clinical trials.
      C. Please elaborate with IND studies. IND holders are the responsible party so therefore the RP should be indicated as S-I.”

      Thank you, April. I should have been more clear/precise in my answer.

      For clinical trials conducted under an IND:
      According to the Elaboration of Definitions of Responsible Party and Applicable Clinical Trial document (http://prsinfo.clinicaltrials.gov/ElaborationsOnDefinitions.pdf), a Sponsor is an entity that initiates a clinical investigation, but does not actually conduct the investigation. Examples of Sponsors could include individuals, corporations, academic medical centers, grantee contractors, awardees, and so on. If the entity holds the IND and is something other than an individual (e.g., academic medical center) and uses its own employee(s) to conduct a clinical investigation, that entity is considered to be a Sponsor (not a Sponsor-Investigator), and the employees are considered investigators. Sponsors may delegate authority to Principal Investigators to be the Responsible Party.
      Additionally, Sponsors may choose to retain the role of Responsible Party if the Principal Investigator cannot be designated as the Responsible Party (e.g., cannot or does not have has access to and control over the data, does not have the right to publish the results of the trial, or cannot meet all of the requirements for the submission of clinical trial information).
      A Sponsor-Investigator is an individual who both initiates and actually conducts, alone or with others, a clinical investigation. Sponsor-Investigators who hold INDs are considered the Responsible Party.

      For clinical trials NOT conducted under an IND:
      The Sponsor is the person/entity that initiated the trial. If the person/entity received research assistance funding such as a grant or sponsored research agreement, the funding recipient generally will be considered the Sponsor. The Sponsor is the Responsible Party unless it delegates that role to the Principal Investigator.
      If the clinical trial is conducted by an entity under a procurement funding agreement (e.g., a contract), the funder is generally considered the Sponsor. The Sponsor is the Responsible Party unless it delegates that role to the Principal Investigator.
      If no funding agreement supports the clinical trial, the person/entity who initiates the trial (i.e., prepared and/or planned the trial) and has appropriate authority/control over the trial to carry out the responsibilities under FDAAA, that person/entity is the Sponsor and the Responsible Party. The Sponsor may delegate the Principal Investigator to be the Responsible Party.

      “Q: Is an observational study that is collecting data on patients who may or may not have taken an investigational product considered to be a clinical trial? The sponsor I am working with claims this would qualify as a clinical trial but I don’t agree. Please advise.
      A: Observational studies are not currently required to be registered/reported on ClinicalTrials.gov by FDAAA. The ICMJE may have a different opinion because subjects are receiving interventions.
      C:What is ICMJE’s opinion?”

      Per its website (http://www.icmje.org/publishing_10register.html), the ICMJE defines a clinical trial as any research project that prospectively assigns human subjects to intervention or concurrent comparison or control groups to study the cause-and-effect relationship between a medical intervention and a health outcome. Medical interventions include drugs, surgical procedures, devices, behavioral treatments, process-of-care changes, and the like. In its FAQ document (http://www.icmje.org/faq_clinical.html), the ICMJE says that “Purely observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) will not require registration.”

      “Q: At our academic institution, we register most clinical research projects whether they are ACTs or not. So, if I understand you correctly, results are not required for those trials that are not ACTs. How do we make that distinction in the posting so that it doesn’t appear that the posting is incomplete (missing results)?
      A: ClinicalTrials.gov does not make a public distinction between what is/is not an ACT. Internally, at your institution, you should consider employing or developing a tracking/compliance method to ensure that you are posting results to applicable clinical trials in the time frame required.
      C: ClinicalTrials.gov will notify you if the study needs results. Check the “problems” list. Unfortunately there is not public reference to what is required to post results.”

      While ClinicalTrials.gov staff may “flag” on the Problems Report that a trial that the sponsor has indicated is a FDAAA Section 801 trial (see the section of the Protocol Data Element Definitions pertaining to Section 801 [http://prsinfo.clinicaltrials.gov/definitions.html]) and needs attention (e.g., results have not been submitted within the legal time frame), ClinicalTrials.gov does not make determinations of whether trials are Applicable Clinical Trials.

      “Q: If a study is prematurely closed (for any number of reasons) and an analysis is not done, how should we record that in ClinicalTrials.gov? Does it matter if there are no subjects enrolled, vs. some subjects enrolled?
      A: Trials that terminate prematurely must still indicate that the trial is closed via the “Enrollment Status” field and a brief explanation of why the study was terminated should be provided. If you collected data during the trial and the trial meets the definition of an applicable clinical trial, results must be reported on ClinicalTrials.gov. A good example of this is NCT00004500, which was terminated early.
      C: Studies that terminate early because of no accrual should indicate the status as “withdrawn” and therefore no results will need to be posted. Other reasons for termination with accrual will still need results posted.”


      Yes, in cases in which no participants actually entered the study, the enrollment status would be “Withdrawn.” Please see the section pertaining to “Overall Recruitment Status” in the Protocol Data Element Definitions (http://prsinfo.clinicaltrials.gov/definitions.html) for additional information.

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