Post on 22-Nov-2014
description
2nd European Clinical Data Disclosure Summit
HighlightsSeptember 9-10, 2010
Berlin, Germany
Topics to be discussed…..The European process
◦EudraCT and beyondThe “Multiple Registries” problem
◦Native language◦Emerging registries
Updates and changes to ClinicalTrials.govTechnologyHL7Competitive intelligence
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The protocol is approved
Sorry, but the title exceeds the
maximum number of characters
allowed by the NIH
Is it MeSH or MeDRA Terms ?
I’m working on the
translation for my
local registry
Advantages of a National Registry
Information publicly available in the national language
Users have access to the country’s data as a wholeEasy data retrieval without consultation of several
(international) registriesNational registries provide transparency for the
country’s population, inspiring confidencePromote clinical research
Advantages of a National Registry Overview and evaluation of clinical research in the
specific country Specification of data entry and access to all data
enables data analysis as needed Enable benchmarking compared to other countries Identify neglected areas of clinical research Serve as a basis for funding policy decisions Serve as a WHO primary registry, enabling academic
sponsors to comply with the ICMJE requirements (International Committee of medical Journal Editors)
Requirements of a bilingual RegistryData in national language
◦to inform the national publicData in English
◦for enabling international data exchange◦to collaborate in meta-registries◦To enable international analyses
how to alleviate bilingual data entries?
Cooperation - StructureDecision of the German Ethics Committees Association:
collection of all 20 WHO parameters (minimal data set)Ethics committees launch web portal, which
◦serves as one single contact point when submitting application forms and registering clinical trials for all types of clinical studies
◦allows and supports online completion of forms◦helps to avoid extra work◦provides structured electronic data and/or pdf
Web-PortalShould be the place to go when submitting and
registering trials (drug trials (AMG), medical device trials (MPG), other trials (non AMG/MPG))
Supports the submitter◦filling in the EC-application ◦registering with the DRKS
Should prevent redundant workShould provide structured electronic data
Form Depending on Type of Trial
------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------
• ------• ------• ------• ------• ------• ------• ------• ------• ------
Module 1/EudraCT
Module 2 and additionalWHO-Parameters
XML-file
Completeonline
Trials on medicinal products Non-drug trials
Completeonline
Modified module 2 and additionalWHO-Parameters
DRKS Interface ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------ ------
Modul 1/EudraCT
XML-file
Ethics committees web portal DRKSform
• ------
• ------
• ------
• ------
• ------• ------
• ------• ------• ------• ------
Completeonline
Module 2 and additionalWHO-parameters
The Future for German applicants?
Web-PortalEthicsCommittees
PEI
BfArM
DRKS
EudraCT
International and National CooperationCooperate closely with the International Clinical
Trials Register Platform (ICTRP; WHO) and adhere strictly to international standardisation (use ICTRP data format)
Obtained status as a WHO Primary RegistryFulfilled ICMJE requirements → ICMJE-compliant
registration in GermanyCooperate efficiently with existing registers;
establish processes to share data with partner registries
Member of EudraCT Joint Operations Group at European Medicines Agency
Data ExchangePrerequisiteConsistent data collection
Identical parameter Identical content Identical select list/catalog
◦Data format XML Other structured formats
In Detail
European Medicines Agency◦Phase (Trial Type)
WHO◦Phase
• N/A• 0 (exploratory trials)• 1• 1-2• 2 • 2-3• 3• 4
E.7.1 Human pharmacology (Phase I) E.7.1.1 First administration to humans E.7.1.2 Bioequivalence study E.7.1.3 Other:E.7.1.3.1 If other, please specify
E.7.2 Therapeutic exploratory (Phase II)E.7.3 Therapeutic confirmatory (Phase III)E.7.4 Therapeutic use (Phase IV)
In Detail
EMA◦Phase (Trial Type)
WHO◦Phase
• N/A• 0 (exploratory trials)• 1• 1-2• 2 • 2-3• 3• 4
E.7.1 Human pharmacology (Phase I) E.7.1.1 First administration to humans E.7.1.2 Bioequivalence study E.7.1.3 Other:E.7.1.3.1 If other, please specify
E.7.2 Therapeutic exploratory (Phase II)E.7.3 Therapeutic confirmatory (Phase III)E.7.4 Therapeutic use (Phase IV)
Coding / Standardized Data Entry Data is standardized and coded using existing international
coding systems wherever possible to◦avoid typing errors◦allow automated quality assurance procedures◦allow data exchange◦allow data analysis
Data entry only in one language needed◦Exception: 11 (free text) parameters need double entry
in English and German (e.g. title, brief summary in lay language, interventions, outcomes, inclusion and exclusion criteria)
Automation in updating the dynamic data on clinicaltrials.gov
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Study status update and sites registrationMultiple Monthly Updates of the overall
studies status with study start/endMultiple Monthly Updates of all the sites
participating to the studies (for recruiting studies only)
Status & sites
update(monthly)
CTMS
Previous posting
Gap Analysis +
consistency checking
About 5000 active Investigators
10% to update every month
XML outputs
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Main advantages of the applicationOld Method New Method
Manual registration of the countries enrolled from the data available in the CTMS
Automatic data collection of the countries & sites from the CTMS
Difficulties to identify the study status to be updated
The system detects and calculates the study status to be updated
Sites registration was not possible (too many data)
- Registration at site level now possible- A single upload of XML to update several studies with sites and their status at the same time
Applicable Clinical Trials…generally include 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 U.S, involves a drug, biologic, or device that is manufactured in the US (or its territories), or is conducted under an investigational new drug application (IND) or investigational device exemption (IDE)
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Delayed Submission of ResultsFDAAA allows for Delayed Submission of Results via:• Certification; or• Request for Extension
CertificationA responsible party may submit a certification for delayed submission of results information for an applicable clinical trial that is: • Completed before the drug or device is initially approved,
licensed, or cleared by the FDA ("seeking initial approval"), or
• Studying a new use of an FDA-approved drug or device (i.e., a use not included in the labeling) for which the manufacturer of a drug or device is the sponsor of the trial and has filed or will file within a year an application to the FDA for approval or clearance of that use ("seeking approval for a new use")
Sept 10, 2010Confidential - 180 Global Consulting, LLC 21
Delayed Submission of Results
Request for ExtensionAllows the Director of NIH to provide an extension of the deadline for submission of results information for an applicable clinical trial if the responsible party submits a written request that demonstrates good cause for the extension and provides an estimate of the date on which the results information will be submitted.
When: not later than one (1) year after the earlier of the estimated or actual completion date (PCD) of the trial
Sept 10, 2010Confidential - 180 Global Consulting, LLC 22
Results data elements◦ Results Point of Contact◦ Certain Agreements ◦ Participants Flow◦ Baseline Characteristics◦ Outcome Measures
Statistical Analysis◦ Limitation and Caveat ◦ Adverse Events
Serious Adverse Events◦ – Table of anticipated & unanticipated serious adverse events◦ – Grouped by organ system◦ – Number and frequency of event in each clinical trial arm
Non-Serious Adverse Events◦ Exceed a frequency of 5 percent within any trial arm
Sept 10, 2010Confidential - 180 Global Consulting, LLC 23
Results Disclosure ProcessEl
igib
ilityFDA
RegulatedApplicable Clinical TrialPCD on or after 9-27-07
Prep
arat
ion Create
PRS accountAssign rolesCommunicate to clinical teamTraining
Data
Ent
ryResults xml generationManual data entry
Revi
ew/A
ppro
veReview data for consistency Approve data for disclosure
Rele
ase
or su
bmitRelease
data to clinicaltrials.gov M
onito
r for
QAExpect
QA commentsModify results with team and re-release
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1-3 cycles
Entering Results in PRSOption 1 – Manual data entry directly in the PRS
system◦Test – https://prstest.nlm.nih.gov◦Live – https://register.clinicaltrials.gov
Option 2 – xml upload using the PRS upload function
You must first…◦Request PRS login account as administrator◦Protocol must have NCT # for results entry (except in
PRS Test system)
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Helpful Hints
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Spell out term when first used, acronym in parentheses Use precise language
Do not use “proportion” unless providing a ratio Do not use “rate" unless providing a quantity in relation to
another unit (e.g., participants per unit time) If simply reporting the number of participants, use “number”
for Measure Type In general, spell out symbols such as –
“Percentage” for “%” , “Number” for “#” For measures obtained using a scale -
Name of scale is provided in “Measure Title.” Range and direction of scores (0 = worst; 10 = best) are
indicated in “Measure Description.” “Unit of Measure” is “units on a scale” if no other unit
ClinicalTrials.gov Results Posted*(2009 vs 2010)
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* Data provided by Clinicaltrials.gov As of September 2010 – over 95,000 trials registered on Clincaltrials.gov
What’s new in the Clinicaltrials.gov PRS? New Results Outcome Measure Fields (Sept. 1)
◦ Optional "Type of Units Analyzed" and "Number of Units Analyzed" (per arm/group) for an outcome measure. Use these new fields when the basis for outcome measure analysis is not participants.
Minor Results Display Changes (Sept. 1)◦ In the Results Participant Flow section, the total for all Arm/Groups
(i.e. sum per row) is automatically computed and displayed for each Milestone and "Reason Not Completed".
◦ A new expanded adverse events display is available on the "Results Overview" screen
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What’s on the Horizon?Expanded Results by Rulemaking
FDAAA requires NIH to issue regulations by 27 September 2010 expanding the Registry and Results Data Bank
Issues to be addressed in the rulemaking …1) Inclusion of results for “unapproved products”2) Technical and non-technical summaries 3) Copy of “full” protocol when results are submitted4) Increasing the timeline for submitting results from 12 to 18 months after the earlier of the estimated completion date of the trial or the actual date of completion
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Trial Data Disclosure: IT Perspective
The Value of Consistency
Infrastructure – Data SourcesClinical Trial Management Information
◦ Clinical Trial Management System (CTMS)◦ Clinical Trial Database◦ Trial Spreadsheets
Trial disclosure data collection formsProtocol/Clinical Study ReportClinical Data Management System (CDMS) such as
SASPharmacovigilance System
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Infrastructure – Data Destination Registries
◦ Clincaltrials.gov◦ EudraCT (CTA)◦ India◦ Italy◦ Australia/New Zealand◦ Etc.
Company Trial WebsitePublicationsForm 3674Clinical Trial Insurance Application FormsPatient Recruitment Call Centers
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1. What are your main data sources
2. In what other systems/processes do you use disclosure data
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Departments Responsible for Posting
April 8, 2023Trial Data Disclosure: IT Perspective 34
Department Primarily Responsible for RegistrationClinical OperationsRegulatory AffairsClinical Sciences / Clinical R&DMedical WritingMedical AffairsClinical Communications and StandardsDepartment Primarily Responsible for ResultsRegulatory AffairsClinical OperationsBiostatisticsMedical and Scientific AffairsPublicationClinical R&DMedical WritingClinical Communications and Standards
Trial Disclosure - Stakeholders
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Challenges of Manual Entry
•Often over 250 data points to manually enter into public database
•Clinical teams have often moved on to other studies and now have to regroup to enter data
•Timely•Risk in quality of manually entered data
•Risk of inconsistency with Clinical Study Reports (CSRs) and publications
•Quality control is very lengthy in order to ensure accuracy
Challenges of manual data
entry to a public
database
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Lesson LearnedNeed to automate data capture to
improve:Accuracy
Efficiency
Consistency
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Comparison With Clinical Study Report Preparation
At one time, medical writers would enter statistical data into CSRs
Statisticians and programmers suggested process to automate importation of statistical results to CSR to avoid manual entry by Medical Writers◦ Conversion of Statistical Analysis System
(SAS) data into rich text format (RTF) tables◦ Copy and paste into CSRs◦ QC validation
Desire to have analogous process for Clinical Registry process
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Getting Started
Determine xml capability of the public database
Determine whether xml
upload must be total or may be partial for the
public database
Determine a workflow to
incorporate the input of text in addition to the
statistical data, if necessary
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Determine Required Data
Data NeededParticipant flow
Baseline and demographic
characteristics
Primary outcome measures
Secondary outcome measures
Serious adverse events
Other adverse events
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Build Into Statistical Workflows
Determine milestones in study timeline
• Dataset creation
Develop templates and layouts of SAS datasets for the various scenarios that will be encountered
• Number of study arms• Stratification, if applicable• Type of study (eg, crossover, parallel)• Incorporate data requirements and terminology that
must be used for the public database
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Develop Final Clinical Trial Analysis Datasets in SAS Format
Define SAS datasets based on the requirements of the public database
Develop set of SAS macros to:◦ Create the datasets from clinical trial SAS
database◦ Create an xml file from the datasets according to
the schema of the public databaseDevelop and use QC tool to validate the xml
file according to the public database schema and contents of the xml file
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“Basic Results” Disclosure to a Public Database
Current Strategies to Facilitate the Process
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•Standardized templates for communication•Central Help Desk support Communication With our Customers
•On-boarding of new contacts or new operating companies•Community of practice meetings are held to share best
practices •Central shared access for training materials using Microsoft
SharepointCustomer
Focus
Automation in the Future
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• User-friendly dashboard • Automated workflows • Automated technical quality checks• E-signature • Automation of text to supplement data
A fully automated process facilitating
transfer of data to the various public
databases in consistent manner
• Efficiency and accountability• Reporting capabilities• Tracking• Transparency• Data accuracy• Consistency• Optimized compliance
Benefits
Clinical Registry Processes – Future Considerations for Automation
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Linking statistical, clinical ,and regulatory
databases to Clinical Registry
Linking product dictionary database•Automated feed of molecule data•Provide NCT# automatically
Linking to the publication system•PubMed information is automated
•Central checkpoint for consistent publication
Integration of existing systems that benefits the entire organization
Still have any questions? For additional information on ExL Pharma’s Clinical Data
Disclosure Summits, please visit www.exlpharma.com