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Presenting a live 90-minute webinar with interactive Q&A

Clinical Trials and Human Research: Complying With New Regulatory Obligations

Navigating New Requirements for Informed Consent, Disclosures, Data-Sharing, and More

Today’s faculty features:

1pm Eastern | 12pm Central | 11am Mountain | 10am Pacific WEDNESDAY, JANUARY 18, 2017

David Peloquin, Esq., Ropes & Gray, Boston Thomas D. Shrack, Esq.,Hall Render Killian Heath & Lyman, Indianapolis

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ROPES & GRAY LLP

Clinical Trials & Human Subjects Research

New Regulations and Guidance

David Peloquin 617.951.7786 david.peloquin@ropesgray.com

ROPES & GRAY

Agenda

• Changes for Clinical Research in the 21st

Century Cures Act (the “Act”)

• FDA/OHRP Final Guidance on Electronic

Informed Consent

6

ROPES & GRAY

21st Century Cures Act

• Signed into law by President Barack

Obama on December 13, 2016

– Contains several important changes for the healthcare, pharmaceutical and medical device industries

• Promoting Drug Development
• Medical Device Innovation
• Digital Health
• Reimbursement/Fraud & Abuse
• Regulation of Clinical Research

7

ROPES & GRAY

21st Century Cures Act

• Harmonizing FDA Human Subject

Regulations and the Common Rule (Section 3023)

– HHS Secretary required to make modifications to both sets of regulations to:

• Reduce regulatory duplication/unnecessary delays
• Modernize for multisite and cooperative research
• Protect vulnerable populations, incorporate local

considerations and support community engagement

– Timeline: Completion by December 2019

8

ROPES & GRAY

21st Century Cures Act

• Waiver or Alteration of Informed Consent

for Minimal Risk FDA-Regulated Studies (Section 3024)

– Food, Drug & Cosmetic Act (FDCA) historically limits IRB ability to waive informed consent

• Drugs: Consent not feasible or contrary to best

interests of human beings

• Devices: Life threatening situation necessitating

use of the device and not feasible to obtain consent from subject or representative

9

ROPES & GRAY

21st Century Cures Act

– The Act amends the FDCA to permit IRBs to waive or alter informed consent requirements for both drug and device clinical investigations if the clinical testing:

• Poses no more than “minimal risk” to the human

subject; and

• Includes appropriate safeguards to protect the

rights, safety, and welfare of the human subjects

– Requires regulation for implementation

• Permits flexibility to mirror Common Rule waiver

criteria

10

ROPES & GRAY

21st Century Cures Act

• Central IRBs for Medical Device Studies

(Section 3056)

– The Act removes FDCA requirement that medical device investigations be overseen by a “local” IRB

• Does not mandate use of a central IRB, but rather

provides flexibility for use of central IRBs in device studies

• Local IRBs may still provide central IRB with input

regarding local considerations

• Does not require regulations for implementation

11

ROPES & GRAY

21st Century Cures Act

• Reducing Administrative Burdens for

Researchers (Section 2034)

– Requires HHS Secretary to review policies of all research funding agencies on disclosure of financial conflicts of interest (“FCOI”) and consider:

• Modifying timelines for reporting to “just-in-time”
• Ensuring requirements are appropriate for awards

directly funding research

• Updating NIH training modules related to FCOI

disclosures

12

ROPES & GRAY

21st Century Cures Act

– Requires NIH Director to implement measures to reduce monitoring obligations of “prime” grant awardees by considering:

• Alternative grant structures that remove need for

subrecipients

• Exemption from subrecipient monitoring if:

– Subrecipient subject to federal audit requirements in the Uniform Guidance; – Primary awardee conducts a pre-award evaluation of each subrecipient’s risk of noncompliance; and – Primary awardee remains liable for subrecipient misconduct

13

ROPES & GRAY

21st Century Cures Act

– Requires FDA Commissioner, HHS Secretary and Secretary of Agriculture to review and revise regulations and policies governing the care and use of laboratory animals to reduce administrative burden, by taking steps to:

• Identify ways to ensure policies are not

inconsistent, overlapping or duplicative and eliminate any such characteristics

• Improve coordination of regulations and policies

14

ROPES & GRAY

21st Century Cures Act

• Changes to Privacy Regulations (Sections

2063, 2012)

– HIPAA’s “preparatory to research” provision prohibits researchers from removing protected health information (“PHI”) from covered entity when performing review preparatory to research – The Act requires HHS to issue guidance clarifying that the HIPAA Privacy Rule does not prohibit remote access if:

• Security/privacy safeguards of rule are respected
• PHI not copied or retained by researcher

15

ROPES & GRAY

21st Century Cures Act

– The Act requires HHS to issue HIPAA authorization guidance

• Clarifying circumstances under which authorization

for use/disclosure of PHI for future research contains sufficient description of use/disclosure

• Clarifying when it may be appropriate to provide

annual notice to individual reminding of right to revoke authorization

• Clarifying appropriate mechanisms for

revocation of authorization for future research

– Requires HHS to convene working group to review uses/disclosure of PHI for research

16

ROPES & GRAY

21st Century Cures Act

• Changes to Certificates of Confidentiality

(“CoC”) (Section 2012)

– At present, HHS has discretionary authority to issue CoCs for research – The Act requires HHS to issue a CoC in connection with federally funded research that collects “indentifiable sensitive information” (“ISI”)

• ISI includes information on mental health and

alcohol and psychoactive drug use

• Secretary retains discretion to issue CoC for non-

federally funded research involving ISI

17

ROPES & GRAY

21st Century Cures Act

– The Act further clarifies that the CoC will prevent release of any information for which there is even “a very small risk, as determined by current scientific practices or statistical methods” of identification – ISI may still be disclosed, if:

• Required by law;
• Necessary for medical treatment of individual;
• Individual consents to disclosure; or
• Disclosure made for purposes of other scientific

research in compliance with applicable federal regulations on human subjects protection

18

ROPES & GRAY

21st Century Cures Act

• Protections from Freedom of Information

Act (FOIA) Disclosures (Section 2013)

– Permits HHS to exempt from FOIA disclosures certain biomedical information collected in research if (i) individual is identified, or (ii) there is at least a “very small risk, as determined by current scientific practices or statistical methods”

• f identification

– Determination must be made in writing, include a statement of the basis for the determination, and be provided to the public upon request

19

ROPES & GRAY

21st Century Cures Act

• Expanded Access Policies for

Investigational Drugs (Section 3032)

– Requires manufacturers and distributors of investigational drugs for diagnosis or treatment or serious diseases to make expanded access policies publicly available and include:

• Contact information for manufacturer/Procedures

for submitting request

• General criteria used to evaluate requests
• Length of time to acknowledge receipt of request
• Hyperlink to clinicaltrials.gov entry for study

–

20

ROPES & GRAY

21st Century Cures Act

• Data Sharing by NIH Award Recipients

(Section 2014)

– NIH may require award recipients to share, to the extent feasible, scientific data generated with the award

• Sharing must be consistent with applicable federal

law and regulations on privacy, security, and informed consent

• Exception for privileged or confidential trade

secret, commercial or financial information

21

ROPES & GRAY

21st Century Cures Act

• Increased Inclusion of Underrepresented

Populations in Clinical Trials (Section 2044)

– Encourages National Institute on Minority Health and Health Disparities to include in its strategic plan ways to increase enrollment of underrepresented populations in clinical research

22

ROPES & GRAY

FDA/OHRP Guidance on Electronic Informed Consent

• Final guidance document on electronic

informed consent (eIC) issued in December 2016

– Finalizes draft guidance issued by FDA in consultation with OHRP in March 2015 – Drafted in response to interest by research community in:

• Using electronic media to provide information

usually contained within written informed consent documents; and

• Obtaining electronic signature on consent

23

ROPES & GRAY

FDA/OHRP Guidance on Electronic Informed Consent

• What is eIC?

– Using electronic systems and processes that may employ multiple electronic media (e.g., text, graphics, audio, video, podcasts and interactive Web sites, biological recognition devices, and card readers) to convey information related to the study and to obtain and document informed consent

• Guidance notes areas where OHRP

(Common Rule) and FDA requirements differ

24

ROPES & GRAY

FDA/OHRP Guidance on Electronic Informed Consent

• Recruitment

– Reiterates that both FDA and OHRP take the position that the informed consent process begins with subject recruitment – States that subject recruitment is outside of the scope of the guidance

• Directs readers to existing FDA’s existing

information sheet on Recruiting Study Subjects: http://www.fda.gov/RegulatoryInformation/Guidanc es/ucm126428.htm

25

ROPES & GRAY

FDA/OHRP Guidance on Electronic Informed Consent

• Benefits of eIC:

– Interactive interface may facilitate subject’s ability to comprehend information – More rapid communication with subjects of updates that could affect willingness to participate in research – More timely entry of eIC into study database – Less difficult to collect subject’s consent at remote locations

26

ROPES & GRAY

FDA/OHRP Guidance on Electronic Informed Consent

• Location of eIC

– At a clinical trial site, e.g., presenting the consent form to the subject on an electronic tablet – Remotely, e.g., subject can access the eIC form in his or her home – Regardless, must provide subjects sufficient

• pportunity to consider whether or not to

participate and to ask questions

• Electronic messaging
• Video conferencing
• Chat function

27

ROPES & GRAY

FDA/OHRP Guidance on Electronic Informed Consent

• Can eIC be the only method of consent
• ffered for a trial?

– Guidance suggests that eIC may not be appropriate for all subjects

• “[S]ubjects should have the option to use paper-

based or electronic informed consent methods completely or partially throughout the informed consent process.”

28

ROPES & GRAY

FDA/OHRP Guidance on Electronic Informed Consent

• Use of Electronic Signatures

– Common Rule

• Permitted if valid in jurisdiction where obtained

– FDA

• Must comply with requirements of 21 C.F.R. pt. 11

and capture/record date on which consent given

• Several options available, including:

– Machine-readable identification card – Biometrics – Digital signatures – User name/password combination

29

ROPES & GRAY

FDA/OHRP Guidance on Electronic Informed Consent

• Subject Copies

– Subjects/legally authorized representatives must be given a copy of the form after it is signed – May be provided in paper or electronic form, e.g., may be provided via email – Any hyperlinks in copy provided to subject must be maintained until study completion – If paper form provided, must contain all information provided electronically (e.g., information appearing in a podcast)

30

ROPES & GRAY

FDA/OHRP Guidance on Electronic Informed Consent

• Verification of Subject Identity

– Common Rule

• Risk-based approach; not required in all instances

– FDA

• Requires that identity of individual be verified

before electronic signature is certified

• If consent obtained at study site, verification can

be done through traditional methods

• If remote verification, flexibility:

– Video conferencing viewing of government ID – Use of security questions

31

ROPES & GRAY

FDA/OHRP Guidance on Electronic Informed Consent

• Pediatric Studies

– Parental permission may be obtained in line with eIC guidelines – Electronic means can be used to obtain the child’s assent – For FDA studies, if child lacks method to verify identity remotely (e.g., no government-issued ID), identity can be verified at first study visit

32

ROPES & GRAY

FDA/OHRP Guidance on Electronic Informed Consent

• HIPAA

– HIPAA authorization can be obtained electronically – If maintained by covered entity or business associate, the signed eIC is PHI subject to Privacy, Security, and Breach Notification Rules

33

ROPES & GRAY

FDA/OHRP Guidance on Electronic Informed Consent

• IRB Role

– Must be provided with an electronic copy of the eIC, including any videos or web-based presentations – Should assess usability of eIC materials to ensure they are easy to navigate – Must review all hyperlinked information, and maintain a copy of the version reviewed by the IRB in either electronic or hard copy

34

Clinical Trials & Human Subjects Research

New Regulations and Guidance

Thomas D Shrack, JD

Hall, Render, Killian, Heath & Lyman, PC 500 North Meridian Street, Suite 40 Indianapolis, Indiana (317) 977-1496 tshrack@hallrender.com

36

Agenda

 HHS Final Rule - Clinical Trials Registration and

Results Information Submission (the “Final Rule”)

 NIH Policy on the Dissemination of NIH-Funded

Clinical Trial Information

 NIH Policy on Good Clinical Practice Training for

NIH Awardees Involved in NIH-funded Clinical Trials

37

Clinical Trials Registration and Results Submission

 Background

 ClinicalTrials.gov is the national registry of federally and

privately supported research studies conducted in the United States and around the world

 The U.S. National Institutes of Health (NIH), through its

National Library of Medicine (NLM), has developed this site in collaboration with the Food and Drug Administration (FDA), as a result of the FDA Modernization Act, which was passed into law in November 1997

 The rationale for ClinicalTrials.gov:

 Increase research transparency  Help people find trials  Reduce duplication of effort

38

Clinical Trials Registration and Results Submission

 Background

 Before the Final Rule, investigators and sponsors determined

which results would be reported and when

 As a result, many studies’ results were never reported  Often, there was cherry picking of outcome measures and adverse

events to be reported

 Under the Final Rule (and the new NIH policy), registration and

results reporting must be done on legally defined timeline

 This will provide greater transparency into human subjects

research conducted in the US

39

Clinical Trials Registration and Results Submission

 Final Rule – Overview

 On September 16, 2016, the Public Health Service issued a

“Final Rule,” 45 CFR Part 11, expanding the requirements for registration and submission of results with ClinicalTrials.gov for “Applicable Clinical Trials.”

 Effective date of Final Rule: January 18, 2017 – today!

(responsible parties will have until April 18, 2017 to comply)

 Study Start Date on or after January 18, 2017 – subject to Final

Rule

 Primary Completion Date on or after January 18, 2017 – subject to

Final Rule

40

Clinical Trials Registration and Results Submission

 Final Rule – Overview

 The Final Rule requires registration and results submission for

applicable clinical trials

Permits posting of registration information for applicable clinical

trials of unapproved or uncleared device products

 The Final Rule expands results reporting requirements to include

trials of unapproved products

 The Final Rule clarifies and expands required results elements to

be reported

Requires submission of protocol (and statistical analysis plan) at

time of results information submission

41

Clinical Trials Registration and Results Submission

 Final Rule – Overview

 Submission of narrative summaries will not be required under

the Final Rule

 The Quality Control and posting process are updated for clarity

and to assist in meeting timelines

42

Clinical Trials Registration and Results Submission

 Final Rule – “Applicable Clinical Trials”

 Definition (42 CFR 11.10)

 Must be “interventional”  Drug (incl. biologics) or Device regulated by FDA (§505 of FDC Act

• r §351 of PHS Act; §510(k), §515 or §520(m) of FDC Act)

 Not Phase 1 (Drugs) or feasibility (Devices) studies  Either: facility located in US; FDA investigational new drug

application (IND) or investigational device exemption (IDE) Number; or drug/device manufactured/exported from US

 Which applicable clinical trials must be registered? (42 CFR

11.22)

 Any initiated after September 27, 2007, or  Those initiated on or before September 27, 2007, with Primary

Completion Date after December 26, 2007 (i.e., ongoing study)

43

Clinical Trials Registration and Results Submission

 Final Rule – “Applicable Clinical Trials”

 When must applicable clinical trials be registered? (42 CFR

11.24)

 Within 21 days of enrollment of 1st subject  Enrollment occurs upon subject’s agreement to participate in the

trial after completing the informed consent process

 Potential subjects who are screened for eligibility but do not

participate in the trial are not considered enrolled, unless otherwise specified by the protocol

44

Clinical Trials Registration and Results Submission

 Final Rule – Registration of Applicable Clinical Trials

 Responsible Party (42 CFR 11.4 and 11.20)

 Each applicable clinical trial must have a responsible party (there

can be no more than one responsible party per trial)

 The sponsor of the clinical trial will be considered the responsible

party unless a principal investigator has been designated the responsible party by the sponsor (42 CFR 11.4(c))

 Who is the sponsor? (42 CFR 11.4)

 IND/IDE Holder – if trial conducted under IND or IDE, the IND/IDE

holder will be considered the sponsor

 No IND or IDE - the single person or entity who initiates the trial,

by preparing and/or planning the trial, and who has authority and control over the trial, will be considered the sponsor

45

Clinical Trials Registration and Results Submission

 Final Rule – Registration of Applicable Clinical Trials

 Clinical Trial Information – What must be submitted? (42 CFR

11.28)

 Study Start Date - Protocol Registration and Results System (PRS)

will rely on Study Start Date to determine which registration information requirements apply

 WARNING label on applicable clinical trial submission page if

required elements are missing or incomplete between 1/18/17- 4/18/17

 ERRORS label on applicable clinical trial submission page if required

elements are missing or incomplete after 4/18/17

46

Clinical Trials Registration and Results Submission

 Final Rule – Registration of Applicable Clinical Trials

 Clinical Trial Information (cont.) (42 CFR 11.28)

 Descriptive Information – includes Brief Title (incl. acronym),

Official Title*, Brief Summary, Primary Purpose*, Study Phase, Study Type, Study Design*, Study Start Date*, Study Completion Date*, Enrollment, Studies FDA-regulated Drug or Device*, Device Product Not Approved or Cleared by U.S. FDA *, etc.

 Outcome Measure Information – each primary and secondary

• utcome measure must be submitted (including name, description*

and time frame)

 Recruitment Information – includes eligibility criteria, sex/gender,

age limits, whether or not the study accepts healthy volunteers*, availability of expanded access*, etc.

* - refers to new element required by the Final Rule

47

Clinical Trials Registration and Results Submission

 Final Rule – Registration of Applicable Clinical Trials

 Clinical Trial Information (cont.) (42 CFR 11.28)

 Location and Contact Information – includes sponsor name,

responsible party (by official title, i.e., Sponsor, Sponsor- Investigator, or Principal Investigator), facility information (name, location, contact)

 Administrative Data – includes unique protocol identification

number, secondary ID (and ID type)*, IND/IDE number, record verification date, human subjects review board status, responsible contact information*, etc.

* - refers to new element required by the Final Rule

48

Clinical Trials Registration and Results Submission

 Final Rule – Registration of Applicable Clinical Trials

 Updating Registration Information (42 CFR 11.64(a)(1))

 For trials initiated before January 18, 2017, registration information

must be updated at least annually; however, must update: (i) Overall Recruitment Status field not later than 30 calendar days after any change and (ii) Primary Completion Date field not later than 30 calendar days after the clinical trial reaches the actual date

 For trials initiated on or after January 18, 2017, registration

information must be updated at least annually; however, the Device Product Not Approved or Cleared by U.S. FDA field must be updated not later than 15 calendar days after a change in approval

• r clearance status, and several fields require 30-day updates

(Study Start Date, Intervention Name, Overall Recruitment Status, Human Subjects Protection Review Board Status, etc.)

 Registration information must also be updated at the time that

results information is initially submitted

49

Clinical Trials Registration and Results Submission

 Final Rule – Submitting Results of Applicable Clinical

Trials

 The responsible party for an applicable clinical trial must submit

clinical trial results information for that trial (42 CFR 11.42)

 Generally, clinical trial results information must be submitted no

later than 1 year after the primary completion date (42 CFR 11.4(a))

 “Primary Completion Date” – (i) date the final subject was

examined or received an intervention for the purposes of final collection of data for the primary outcome, or (ii) if multiple primary

• utcome measures, the date on which data collection is completed

for all of the primary outcomes

50

Clinical Trials Registration and Results Submission

 Final Rule – Submitting Results of Applicable Clinical

Trials

 However, delayed submission is allowable for up to two (2)

years if the drug or device product studied in the trial is not yet approved or the manufacturer is the sponsor and is seeking approval of a new use (42 CFR 11.44(b), (c) and (e)); in such case, the deadline for submission will be 30 calendar days after the earliest of the following:

 FDA approves, licenses, or clears the drug product  FDA issues a letter that ends the regulatory review cycle (for

previously approved drugs and devices)

 the application or premarket notification seeking approval,

licensure, or clearance of the new use is withdrawn without resubmission

51

Clinical Trials Registration and Results Submission

 Final Rule – Submitting Results of Applicable Clinical

Trials

 Clinical Trial Results - What results must be submitted? (42 CFR

11.48)

 Participant Flow – includes Participant Flow Arm Information (title

and description*), Pre-Assignment Information (significant events that occur after enrollment and prior to assignment to an arm)*, Participant Data (# of human subjects that started and completed the clinical trial, by arm, or if assignment is based on a unit other than participants, also include a description of the unit of assignment (e.g., eyes, lesions, implants) and number of units that started and completed the clinical trial, by arm*)

* - refers to new element required by the Final Rule

52

Clinical Trials Registration and Results Submission

 Final Rule – Submitting Results of Applicable Clinical

Trials

 Clinical Trial Results - What results must be submitted? (42 CFR

11.48)

 Demographic and baseline characteristics – includes Baseline

Characteristics Arm/Group Information (Title and Description*), Baseline Analysis Population Information (Overall # of Baseline Participants, Overall # of Units (other than participants) Analyzed*, Baseline Measure Information (age, sex/gender, race and ethnicity*, other measures assessed at baseline and used in the analysis of the primary outcome measure(s)*)

* - refers to new element required by the Final Rule

53

Clinical Trials Registration and Results Submission

 Final Rule – Submitting Results of Applicable Clinical

Trials

 Clinical Trial Results - What results must be submitted? (42 CFR

11.48)

 Outcomes and statistical analyses – includes Outcome Measure

Arm/Group Information (Title and Description*), Analysis Population Information (# of Participants/Units Analyzed), Outcome Measure Information (name, metric used*, assessment time point(s), type (i.e., primary, secondary, other pre-specified, post hoc), unit of measure), Outcome Measure Data, Statistical Analysis Overview (incl. identification of arms compared, type of statistical test conducted - superiority, non-inferiority, equivalence, or

• ther*), and Statistical Test of Hypothesis (p-value and procedure

used) or Method of Estimation (estimation parameter, estimated value, and confidence interval (if calculated))

* - refers to new element required by the Final Rule

54

Clinical Trials Registration and Results Submission

 Final Rule – Submitting Results of Applicable Clinical

Trials

 Clinical Trial Results - What results must be submitted? (42 CFR

11.48)

 Adverse event information – includes all serious adverse events,

adverse events, other than serious adverse events, that exceed a frequency of 5 percent within any arm of the clinical trial, all-cause mortality*, time frame*, collection approach*, etc.

 Protocol and statistical analysis plan – includes a copy of the

protocol (all amendments, cover page with Official Title, NCT number, and date of document; may redact names, addresses, and

• ther personally identifiable information and trade secret and/or

confidential commercial information) and statistical analysis plan (if separate)*

* - refers to new element required by the Final Rule

55

Clinical Trials Registration and Results Submission

 Final Rule – Submitting Results of Applicable Clinical

Trials

 Clinical Trial Results - What results must be submitted? (42 CFR

11.48)

 Administrative Information – includes Results Point of Contact

(name or official title, name of organization, telephone # and email address) and Certain Agreements (between sponsor and principal investigator re: employment, restrictions on publication of results, etc.)

56

Clinical Trials Registration and Results Submission

 Final Rule – Submitting Results of Applicable Clinical

Trials

 Updating Results Information (42 CFR 11.64(a)(2))

 For trials with a Primary Completion Date on or after January 18,

2017 (i.e., subject to 42 CFR 11.48 ), clinical trial results information must be updated at least once per year, except for the protocol and statistical analysis plan and certain agreements

57

Clinical Trials Registration and Results Submission

 Final Rule – Posting and Quality Control Review

Procedures

 Posting of Clinical Trial Registration Information (42 CFR

11.35(a))

 NIH Director will post clinical trial registration information: (i) for

drug trials, not later than 30 calendar days after the responsible party has submitted registration information or (ii) for device trials, not later than 30 calendar days after clinical trial results information is required to be posted (for previously approved devices) or not later than 30 calendar days after the date of FDA approval or clearance, unless responsible party authorizes earlier posting (“opt-

• ut”) (for devices not previously approved or cleared)

 NIH Director will post clinical trial results information not later than

30 calendar days after the responsible party submits the information

58

Clinical Trials Registration and Results Submission

 Final Rule – Posting and Quality Control Review

Procedures

 Quality Control

 Intention is to continue quality control review similar to procedures

currently used (automated system-based check and manual review)

 Information will be posted even if quality control review has not

concluded

 Registration will not receive NCT number until quality control review

has concluded

 Posted record will contain information to make clear process has

not concluded

 Will evaluate ways posted record could specify data element(s) that

may contain errors, deficiencies, and/or inconsistencies

 NIH Director will establish procedures for quality control review

specified at https://prsinfo.clinicaltrials.gov

59

Clinical Trials Registration and Results Submission

 Final Rule – Posting and Quality Control Review

Procedures

 Quality Control

 NIH Director may provide electronic notification to the responsible

party of apparent errors, deficiencies and/or inconsistencies that are identified by quality control review

 The responsible party must correct or address all apparent errors,

deficiencies, and/or inconsistencies (w/in 15 calendar days for registration information, 25 calendar days for results information)

 A responsible party who becomes aware of errors (other than those

identified in the quality control process), shall correct or address such errors (w/in 15 calendar days for registration information, 25 calendar days for results information)

60

Clinical Trials Registration and Results Submission

 Final Rule – Sanctions For Non-Compliance

 What are the Penalties for Non-Compliance?

 The Final Rule does not articulate new grounds for civil or criminal

liability; rather it merely highlights that failure to comply with reporting requirements, as clarified under the Final Rule, may constitute a prohibited act under §301(jj) of the FDC Act

 Civil monetary penalties (up to $10,000/day)  Withholding of grant funds/termination of grants (by NIH)  Public notices of noncompliance and violations  FDA sanctions (i.e., debarment)  Inability to publish in journals following ICMJE policy, and other

select journals

61

NIH Policy - Clinical Trial Information

 NOT-OD-16-149, Fed. Reg. Vol. 81, No. 183, September

16, 2016

 https://www.federalregister.gov/documents/2016/09/21/2016-

22379/nih-policy-on-the-dissemination-of-nih-funded-clinical- trial-information

 Effective January 18, 2017 (today!)  Applies to all NIH-funded clinical trials regardless of study

phase, type of intervention, or whether they are subject to FDA regulations (specifically, the Final Rule we just discussed)

62

NIH Policy - Clinical Trial Information

 All investigators conducting clinical trials funded in whole or in

part by NIH will:

 ensure that these trials are registered at ClinicalTrials.gov, within

21 calendar days after the enrollment of the first participant

 submit results information of these trials to ClinicalTrials.gov, within

• ne year after the trial’s primary completion date

 Applications for NIH funding for any clinical trial submitted on or

after January 18, 2017, must include as part of the application a plan for registering trials and submitting results to ClinicalTrials.gov

 In addition, informed consent documents for clinical trials within

all three categories listed in the NIH Policy are to include a specific statement relating to posting of clinical trial information at ClinicalTrials.gov

63

NIH Policy - Clinical Trial Information

 This policy will be part of the terms & conditions of NIH awards

supporting clinical trials

 Failure to comply with the terms and conditions of the NIH

award may provide a basis for enforcement actions, including termination, consistent with 45 CFR 75.371 and/or other authorities, as appropriate

 If the NIH-funded clinical trial is also an applicable clinical trial

under the FDA’s Final Rule, non-compliance with the requirements specified in 42 USC 282(j) and 42 CFR Part 11 may also lead to the actions described in 42 CFR 11.66

64

NIH Policy - Clinical Trial Information

 NIH Guidance and Resources

 http://osp.od.nih.gov/office-clinical-research-and-bioethics-

policy/clinical-research-policy/clinical-trials

 https://grants.nih.gov/clinicaltrials_fdaaa/faq.htm

65

NIH Policy on GCP Training

 NOT-OD-16-148, September 16, 2016

 https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-

148.html

 Effective January 1, 2017  Establishes the expectation that all NIH-funded investigators

and staff who are involved in the conduct, oversight, or management of clinical trials should be trained in Good Clinical Practice (GCP), consistent with principles of the International Conference on Harmonisation (ICH) E6 (R2)

 Applies to NIH-funded investigators and clinical trial site staff

who are responsible for the conduct, management and oversight

• f NIH-funded clinical trials

66

NIH Policy on GCP Training

 GCP training includes the Principles of ICH GCP found in Section

2 of ICH E6

 Training may be achieved through a class or course, academic

training program, or certification from a recognized clinical research professional organization

 Completion of GCP training will demonstrate that individuals

have attained the fundamental knowledge of clinical trial quality standards for designing, conducting, recording and reporting trials that involve human research participants

 GCP training should be refreshed at least every three years in

• rder remain current with regulations, standards and guidelines.

Recipients of GCP training are expected to retain documentation

• f their training