clinical trials registry

Clinical Trials RegistrySusan Koenig, MPP&PA

Director, Office of Compliance & Quality

University of Missouri-Columbia

School of Medicine

Compliance & Quality Seminar Series Presents:

Office of Compliance & Quality, University of Missouri-Columbia School of Medicine

2

Objectives1. Learn the background and importance

of clinical trials registration.

2. Identify clinical trials registration requirements by source and scope.

3. Explore recent and proposed changes in requirements.

4. Review reporting methods including electronic uploads and downloads.


3

Why is a registry important?

WHO:

“ A public, complete and readily searchable registry……will – Further good research practice– Assist in making treatment decisions– Help increase public trust in clinical research”


4


FDAAA (Food & Drug Administration Amendments Act) of 2007:

The Data Bank (clinicaltrials.gov) will– Enhance patient enrollment– Track subsequent progress– Make the registry publicly available– Ensure the registry is searchable on the

Internet


5


NEJM editorial:– “Mandatory registration represents a critical advance in

making clinical trials of new treatments public knowledge.”

– “A decade ago a clinical trial could be conducted in secret…..”

– “With several recent blockbuster drugs…..breakdowns in communication of trial results kept safety concerns from doctors and patients.”


6

Clinical Trials Registry Chronology

• November 1997 – FDA Modernization Act mandates registration

• February 2000 – clinicaltrials.gov available on the Internet

• September 2000 – Medicare NCD (National Coverage Decision) on routine costs of clinical trials allowed IF trial is registered in proposed HCFA registry

• October 2003 – WHO begins dialogue on registration

• September 2004 – ICMJE (International Committee of Medical Journal Editors) endorses WHO initiative

• November 2004 – Trials Registry Platform recommended during WHO Ministerial Summit on Health Research, held in Mexico City

• May 2005 – WHO Trials Registry recommendations approved by the world health Assembly


7

Clinical Trials Registry Chronology

• January 2006 – AAMC (Association of American Medical Colleges) calls for registration

• May 2006 – WHO specifies 20 key data elements for clinical trials registries

• December 2006 – Medicare Coverage Advisory Committee considers using clinicaltrials.gov in lieu of proposed HCFA registry

• June 2007 – ICMJE (NEJM, June 7, 2007) expands and clarifies definition of types of trials to be registered

• September 2007 – FDAAA signed into law

• October 2007 – NEJM reiterates ongoing support for clinical trials registration and the new FDAAA requirements


8

International Committee of Medical Journal Editors

“ICMJE adopts the WHO’s definition of clinical trials 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.’


9


Health-related interventions include any intervention used to modify a biomedical or health-related outcome (for example, drugs, surgical procedures, devices, behavioral treatments, dietary interventions, and process-of-care changes).


10


Health outcomes include any biomedical or health-related measures obtained in patients or participants, including pharmacokinetic measures and adverse events. As previously, purely observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) will not require registration.”


11

Food & Drug Administration Amendments Act of 2007

• Additional clout for the FDA

• Pediatric device & pharmaceutical issues

• Conflict of interest on FDA committees

• Post-market safety of drugs

• Clinical trial data bank


12

FDAAA Major Changes

• Definition expanded

• Phase I excluded

• Data elements expanded

• Results reporting to be initiated


13

Applicable Clinical Trial• Device

– Prospective study of health outcomes– Compare device interventions– Pediatric post-market surveillance studies– Excludes prototype and feasibility studies

• Drug– Controlled clinical investigation– Drug subject to FDA requirements– Excludes Phase I clinical trial


14

Responsible Party

• Sponsor registers one time for ALL sites

• Investigator who is responsible for conducting the trial


15

Data Bank Expansion

Content expanded– Descriptive information– Recruitment information– Location and contact information– Administrative data


16

Data Elements• Descriptive Information

• Brief title, intended for the lay public• Brief summary, intended for the lay public• Primary purpose• Study design• Study phase (for an applicable drug clinical trial)• Study type• Primary disease or condition to be studied, or the focus of

the study• Intervention name and intervention type• Study start date• Expected completion date• Target number of subjects• Outcomes, including primary and secondary outcome

measures


17

Data Elements• Recruitment Information

– Eligibility criteria– Gender– Age limits– Whether the trial accepts healthy volunteers– Overall recruitment status– Individual site status– Whether or not there is expanded access for

those who do not qualify for enrollment


18

Data Elements• Location and Contact Information

– Name of sponsor– Responsible party by official title– Facility name and contact information

• City, state, zip code for each location• Toll-free number


19

Data Elements

• Administrative Data– Unique protocol identification number– Other protocol identification numbers, if any– FDA’s IND/IDE protocol number and record

verification date


20

TimingWhen to register?

Applicable clinical trials register by later of– 90 days after enactment (by December 26,

2007)– 21 days after first patient enrolled


21

Posting of ResultsAfter Drug or Device Approval

Link from clinicaltrials.gov to required informationFDA Information, if applicable

• FDA summary documents• Posted FDA assessments of results• FDA public health advisories• FDA action package of applicable drug• Safety and effectiveness of applicable device

NIH Links• Medline citations• NLM database of product labels


22

Posting of ResultsOne year later, by September 27, 2008

Registry to include data elements and tables– Demographic and baseline data– Primary and secondary outcomes– Point of contact about results– Existence of agreements that restrict release


23

Posting of Results

Three years later, by September 27, 2010

• Future guidance• Public meeting

– 18 months after enactment (by March 2009) – for public input on third year rule making.


24

Adverse Events in Results Data Bank

Regulations must be issued by March, 2009

OR

Adverse Events must be included by September, 2009

Adverse Events – Serious – Frequent (>5% within any arm)– Anticipated & unanticipated


25

Federal Grants• Funded in whole or in part

– DHHS– FDA– NIH– AHRQ

• Must submit registry data and results

• Agencies must verify submission before releasing remaining funds


26

Reporting Methods

Web page clinicaltrials.gov

PRS (Protocol Registration System)


27

Account Application Process

There are two types of PRS accounts: Organization accounts

• multiple users • trials conducted at an organization

Individual accounts • trials conducted by a single investigator


28

Reporting Methods

Logon– Each institution designates a PRS

Administrator– Administrator creates logons– Contact Susan Koenig at

[email protected]


29

Reporting Methods

• Create a Record– Entry is saved, modify as needed– “Complete” –when edits are finished– Modify at any time and mark again as

“complete”

• PRS Administrator will “approve” and “release”


30

Reporting Methods

• Clinicaltrials.gov staff will review before entry is available for public view

• Appear on web site within 2-5 days

• NCT number assigned at that time


31

Reporting MethodsElectronic Reporting

– Records can be uploaded and downloaded– Must be in PRS document format– One upload can contain multiple records– Records with errors are placed in “complete”

status– Modify errors by corrected upload or through

on-line edit


32

Proposed Protocol forHuman Subject Research

IRB Approved? NoYes

Register study on clinicaltrials.gov prior to enrollment activities

Does study assign humans to health-related interventions to evaluate effects on health outcomes? (required

for journal publication)

Yes

No

Does study involve a drug or device clinical trial, excluding Phase I or device prototypes?

(FDA requirement)

Obtain assistance or logon from UM - Columbia clinicaltrials.gov

administrator at [email protected]

No

Yes

No need to register

Clinical Trials RegistrationProcess to navigate sometimes overlapping requirements

University of Missouri - Columbia

Note: Registration of observational studies is optional.

For more information or assistance with registration, contact the Office of Compliance & Quality, University of Missouri - Columbia School of Medicine, 573-882-8957.

For more information about clinicaltrials.gov, visit

Http://prsinfo.clinicaltrials.gov

Does study involve hospital, clinic or ancillary claims

for Medicare beneficiaries?(Medicare requirement) No

For more information about UM-Columbia registration, call

573-882-8957

The sponsor will register

Yes

No

Is this a multi-site trial sponsored by an

outside entity? Yes

Note: Multi-site trials should be registered by the investigator at the lead site.


33

Office of Compliance & Quality

https://sp.missouri.edu/sites/researchbudgetresources/default.aspx

[email protected]

[email protected]

mailto:[email protected]

mailto:[email protected]

clinical trials registry

Documents

trials registry platform

registry important

columbia school of medicinewhy

mandatory registration

health research

icmje nejm

proposed changes

public trust