1. 2nd European Clinical Data Disclosure Summit Highlights September 9-10, 2010 Berlin, Germany

2. Topics to be discussed….. The European process EudraCT and beyond The “Multiple Registries” problem Native language Emerging registries Updates and changes to ClinicalTrials.gov Technology HL7 Competitive intelligence

3. 3 I’m working on the translation for my local registry Sorry, but the title exceeds the maximum number of characters allowed by the NIH The protocol is approved Is it MeSH or MeDRA Terms ?

4. Advantages of a National Registry Information publicly available in the national language Users have access to the country’s data as a whole Easy data retrieval without consultation of several (international) registries National registries provide transparency for the country’s population, inspiring confidence Promote clinical research

5. 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)

6. Requirements of a bilingual Registry Data in national language to inform the national public Data in English for enabling international data exchange to collaborate in meta-registries To enable international analyses  how to alleviate bilingual data entries?

7. Cooperation - Structure Decision 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

8. Web-Portal Should 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 work Should provide structured electronic data

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17. ------Modified module 2 and additional WHO- Parameters Module 2 and additional WHO- Parameters Complete online

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27. ------XML-file Modul 1/ EudraCT Module 2 and additional WHO- parameters

28. The Future for German applicants? Web-Portal DRKS Ethics Committees BfArM EudraCT PEI

29. International and National Cooperation Cooperate 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 Registry Fulfilled ICMJE requirements -> ICMJE-compliant registration in Germany Cooperate efficiently with existing registers; establish processes to share data with partner registries Member of EudraCT Joint Operations Group at European Medicines Agency

30. Data Exchange Prerequisite Consistent data collection Identical parameter Identical content Identical select list/catalog Data format XML Other structured formats

32. 0 (exploratory trials)

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38. 4E.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)

40. 0 (exploratory trials)

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46. 4E.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)

47. 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)

48. Automation in updating the dynamic data on clinicaltrials.gov

49. Studystatus update and sites registration Multiple Monthly Updates of the overallstudiesstatuswithstudystart/end Multiple Monthly Updates of all the sites participating to the studies (for recruitingstudiesonly) 18 CTMS XML outputs Status & sites update (monthly) Previous posting Gap Analysis+ consistencychecking About 5000 active Investigators 10% to update everymonth

50. Main advantages of the application 19

51. 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) 20

54. 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, 2010 Confidential - 180 Global Consulting, LLC 21

55. Delayed Submission of Results Request for Extension Allows 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, 2010 Confidential - 180 Global Consulting, LLC 22

56. 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, 2010 Confidential - 180 Global Consulting, LLC 23

57. Results Disclosure Process 24 1-3 cycles

58. Entering Results in PRS Option 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) 25

60. Use precise language

61. Do not use “proportion” unless providing a ratio

62. Do not use “rate" unless providing a quantity in relation to another unit (e.g., participants per unit time)

63. If simply reporting the number of participants, use “number” for Measure Type

64. In general, spell out symbols such as –

65. “Percentage” for “%” , “Number” for “#”

66. For measures obtained using a scale -

67. Name of scale is provided in “Measure Title.”

68. Range and direction of scores (0 = worst; 10 = best) are indicated in “Measure Description.”

70. 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 28

71. 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 submitted 4) 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 29

72. Trial Data Disclosure: IT Perspective The Value of Consistency

73. Infrastructure – Data Sources Clinical Trial Management Information Clinical Trial Management System (CTMS) Clinical Trial Database Trial Spreadsheets Trial disclosure data collection forms Protocol/Clinical Study Report Clinical Data Management System (CDMS) such as SAS Pharmacovigilance System 31

74. Infrastructure – Data Destination Registries Clincaltrials.gov EudraCT (CTA) India Italy Australia/New Zealand Etc. Company Trial Website Publications Form 3674 Clinical Trial Insurance Application Forms Patient Recruitment Call Centers 32

75. What are your main data sources In what other systems/processes do you use disclosure data 33

76. Departments Responsible for Posting September 24, 2010 Trial Data Disclosure: IT Perspective 34

77. Trial Disclosure - Stakeholders 35

78. Challenges of Manual Entry 36

79. Lesson Learned 37 Need to automate data capture to improve:

80. Comparison With Clinical Study Report Preparation 38 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

81. Getting Started 39

82. Determine Required Data 40

83. Build Into Statistical Workflows 41

84. Develop Final Clinical Trial Analysis Datasets in SAS Format 42 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 database Develop and use QC tool to validate the xml file according to the public database schema and contents of the xml file

85. “Basic Results” Disclosure to a Public Database 43

86. Current Strategies to Facilitate the Process 44

87. Automation in the Future 45

88. Clinical Registry Processes – Future Considerations for Automation 46 Integration of existing systems that benefits the entire organization

89. Still have any questions? For additional information on ExLPharma’s Clinical Data Disclosure Summits, please visit www.exlpharma.com