Clinical Trial Transparency. What is available?

Clinical Trial Transparency What is available? 1

Outline Clinical Trial Data Collection and Reporting Data Definitions Clinical Trial Transparency Summary Report Requirements Example of Results Posting 2

Clinical Trial Data Collection and Reporting 1. What is involved? Data Collection Data Collection Protocol Case Report Modules Database Statistical Analysis/ Programming Statistical Analysis Plan Programming Plan Reporting Listings, Summaries, Figures 3

What Do We Mean When We Talk About? Raw Data Derived Data (Individual) Patient-Level Data 4

Raw Data Raw data means data that have been collected during a study. Raw means that the data is untreated and therefore not the result of any calculation. Example: A raw data item is for example the date of birth or the height measured of a given patient in a study. 5

E.g. Case Report Form Demography module Demography Date of Birth (dd-mmm-yyyy) - - Sex (1) Male Race (1) White (2) Female (2) Black (3) Asian Height (1) In (4) Other (2) cm Specify other Weight (1) lb (2) kg 6

Derived Data Derived data is data that is obtained from raw data and which has undergone a mathematical calculation. Example: Age of Participant Calculated From Date of Birth The Mosteller formula for Body Surface Area: BSA (m²) = ( [Height(cm) x Weight(kg) ]/ 3600 )½ e.g. BSA = SQRT( (cm*kg)/3600 ) 7

(Individual) Patient-Level Data Individual patient-level data (or just patient-level data) is clinical data that has been collected in the context of a clinical trial and is linked to an individual patient. This can be either raw data or derived data. It is anonymised for further processing. 8

Example: Individual Patient Level data (listing) Body Surface Area (BSA) and Age are derived endpoints (calculated from the raw CRF data) 9

Clinical Trial Data Collection and Reporting 2. Statistical Analysis Plan Data Collection Protocol Case Report Modules Database Statistical Analysis/ Programming Statistical Analysis Plan Programming Plan Reporting Listings, Summaries, Figures 10

Statistical Analysis Plan Pre-defines the statistical analyses to be performed on the data from the trial to produce: - Analysis data sets - Summaries of Results in tables, listings and graphs. Statistical analyses support the conclusions drawn from the clinical trial 11

Clinical Trial Data Collection and Reporting 3. Reporting Data Collection Protocol Case Report Modules Database Statistical Analysis/ Programming Statistical Analysis Plan Programming Plan Reporting Listings, Summaries, Figures 12

Analysis Data Sets Analysis datasets contain both raw and derived data and directly supports the assessment of study objectives and reflect analysis and reporting needs. Analysis data sets together with a description of how the raw data was processed are sufficient to allow a third party to repeat, corroborate the results or perform other analyses. T I T L E O F T H E P O W E R P O I N T 13

Example: Report Demographic Summary 14

Clinical Trial Transparency Since 2004, EFPIA and other trade associations and companies have committed to registering all clinical trials on a public registry and disclosing all summary results, positive and negative, of industry-sponsored clinical trials in patients, with full details laid out in a joint position on disclosure of clinical trial information in databases and scientific literature. Information at the following websites: www.clinicaltrialsregister.eu www.clinicaltrials.gov http://clinicaltrials.ifpma.org/clinicaltrials/no_cache/en/myportal/index.htm https://eudract.ema.europa.eu/ 15

What information is currently publicly available? Description of Phase II-IV adult clinical trials (EudraCT, Clinicaltrials.gov) Description of any paediatric trial (EudraCT, Clinicaltrials.gov) Results of Phase II-IV clinical trials, paediatric trials (and some non-interventional studies) (Clinicaltrials.gov) T I T L E O F T H E P O W E R P O I N T 16

European Commission -Technical Guidance on the Summary Report Information to be included for Clinical Trials Trial information: Study identification Sponsor details Paediatric regulatory details Result analysis stage General Information about the trial Population of trial subjects with actual number of subjects included Subject disposition Recruitment Baseline Characteristics Endpoint definitions Statistical Analyses Adverse events information Adverse event reporting group Serious Adverse Events Non-serious adverse events T I T L E O F T H E P O W E R P O I N T 17

How will the Results information be released in EudraCT? Results information for Paediatric trials should be submitted to the EMEA, for entry into EudraCT, no more than 6 months after the last visit of the last subject. Other trials will be submitted within 12 months of the last visit of the last subject. Public release of result-related information will take place automatically once this information has been included by the EMEA in the EudraCT database. The information will be made available through a dedicated public portal called EudraPharm (also links to other international registries, e.g. ClinicalTrials.gov). T I T L E O F T H E P O W E R P O I N T 18

Example of Results Database already available - ClinicalTrials.gov The ClinicalTrials.gov results database was launched by the Food and Drug Administration (FDA) in September 2008 which requires the submission of "basic results" for certain clinical trials, generally not later than one year after the Completion Date (for authorised medicines). 19

ClinicalTrials.gov requirements Requires Results Posting of: Trials of FDA-Approved or cleared drug and devices Phase II-IV drug and device trials for all diseases Timing Within 12 months of Primary Completion Date (PCD) for authorised medicines (or within 30 days of approval of medicine by FDA) www.clinicaltrials.gov

What Summary Report information is required in Clintrials.gov? Tabular data presentations in National Institutes of Health (NIH) pre-determined format consisting of: Baseline characteristics (demographics) Primary Outcomes (primary endpoints in protocol) Secondary Outcomes (secondary endpoints in protocol) Statistical analysis Serious Adverse Events Non-serious Adverse Events

Example of Basic Results posting http://www.clinicaltrials.gov/ct2/show/study/nct00744978?term=pfi zer+alzheimer&rank=8&sect=x6015&view=results 22

Example: Primary Endpoint Result http://www.clinicaltrials.gov/ct2/show/results/nct00744978?term=pfizer+al zheimer&rank=8&sect=x6015#outcome1 23

Example: Serious Adverse Events http://www.clinicaltrials.gov/ct2/show/results/nct00744978?term=p fizer+alzheimer&rank=8&sect=x36015#evnt T I T L E O F T H E P O W E R P O I N T 24

Other Adverse Events http://www.clinicaltrials.gov/ct2/show/results/nct00744978?term=p fizer+alzheimer&rank=8&sect=x436015#othr T I T L E O F T H E P O W E R P O I N T 25

Summary What summary report information is currently disclosed? Phase II-IV adult clinical trials for licensed drugs (clinicaltrials.gov) Paediatric Clinical Trials for licensed drugs (clinicaltrials.gov) Will also be disclosed in EudraCT in 2014 When is it disclosed? Phase II-IV adult clinical trials within 12 months of patient completion date (or within 30 days of approval of medicine for clinicaltrials.gov) Paediatric Clinical Trials usually within 6 months of patient completion date Where can we find the information? www.clinicaltrials.gov https://eudract.ema.europa.eu/ T I T L E O F T H E P O W E R I N T 26

Thank you Questions?

EFPIA Brussels Office Leopold Plaza Building Rue du Trône 108 B-1050 Brussels - Belgium Tel: +32 (0)2 626 25 55 www.efpia.eu