Versioning in Clinical Trials. European Industry MedDRA User Group Meeting March 28 th 2014 Vienna

Transcription

1 Versioning in Clinical Trials European Industry MedDRA User Group Meeting March 28 th 2014 Vienna

2 Background MedDRA is updated every 6 months Sometimes, Clinical trials start and end on different versions Trials end using a version that is no longer current Organisations need to adopt a strategy appropriate to company needs and fulfilling regulatory requirements 2

3 Version Changes During Drug Development Trial A Trial B Trial C Trial D Trial E Trial F MedDRA Mar-12 Sep-12 Mar-13 Sep-13 Mar-14 CM #### 3

4 Types of Changes Changes may relate to any level of the hierarchy, including. New LLTs & PTs Promotions & Demotions of LLT/PT LLT changes in currency status LLTs moved to different PTs PTs moved to different HLTs, may also affect SOC Changes in the hierarchy at HLT & HLGT level Some changes have more impact than others 4

5 Number of Changes Per Release has Declined Terms Added Terms Moved Currency Changes 5

6 Examples of Changes Rash over eyelids Upper lid rash bilateral Facial eruption Feeling irritable Spouse complained patient is grumpy Quickly irritable at slightest thing Eyelid rash Rash Polyneruopathy following shingles Post-herpes polyneuropathy Nerve disorder due to herpes infection Irritability Psychiatric disorders SOC Terms added, made noncurrent and changed SOC in version 17.0 Postherpetc polyneuropathy 6

7 Impact of Version Updates The need to maintain multiple versions in a clinical database and coding tools Coding differences when combining studies in an integrated safety summary meta analysis Reconciliation difficulties between Drug Safety and Clinical coding of SUSARs Differences between annual Development Safety Update Reports (DSURs) 7

8 Purpose of Up-Versioning Trial Data To implement current version in studies To utilise new added medical concepts To remain aligned with regulatory authorities To simplify work with development partners To optimise results of statistical analyses To facilitate communication of safety data 8

9 Regulatory Mandates Safety data - In Europe and Japan, it is mandatory to submit using the current or previous version, so there is a need to upversion Clinical trials data - There are no mandates anywhere globally about versions used With the exception of SUSARs in Europe 9

10 Handling of SUSARs Annual DSURs require PTs, if MedDRA has been used No requirement to update MedDRA version All events may be coded on an outof-date version Clinical Database S Safety Database Latest or previous version is required for ICSRs, PSURs & SUSARs Safety database coding is updated ever 6 months to the latest version of MedDRA SUSARs are expedited from Safety Database for submission to EMA Safety Database always uses the latest version of MedDRA Clinical Database may not be updated There may be a reconciliation mis-match between coding of the same event 10

11 Possible Approaches Options for MedDRA Versioning for Clinical Trials Option 1 Freeze at the initiation and for the life of a project and report with same version of MedDRA. Option 2 Freeze at the initiation of a project and report with most recent version of MedDRA. Option 3 Freeze at the initiation of each trial within a project, and report with the most recent version of MedDRA. Option 4 Hold all coding to the completion of each trial and utilize the most recent version of MedDRA for coding and reporting. Option 5 Freeze at the beginning of each trial within a project and optionally re-code data with the latest version at the conclusion of the trial based on criteria defined within project plan. Always output the data utilizing the most recent version of MedDRA. Option 6 Ongoing re-coding of all trial data in a project to most recent version Take a moment to consider what does your company do? 11

12 Best Practices Guidelines The MedDRA Management Board endorsed as Best Practice a set of documents about MedDRA Versioning Clinical Trials MSSO recommends to re-code with each release option 5/6 Safety Reporting Use the latest version of MedDRA Start using latest version on 1 st Monday of the second month following release 12

13 Standard Levels of Versioning Activities Level A B C D Description Identify verbatim terms linked to non-current LLTs and recode existing data and Recode verbatim terms to new LLTs that are direct or lexical matches and Recode verbatim terms to new LLTs that are medically better matches Identify verbatim terms linked to non-current LLTs and recode existing data and Recode verbatim terms to new LLTs that are direct or lexical matches Identify verbatim terms linked to non-current LLTs and recode existing data Begin to use new version for coding new data; no recoding of existing data As agreed at a MedDRA Blue Ribbon Panel (2009) and in an approved MSSO Best Practices guide to Versioning 13

14 Practical Methods to Version Step 1: Step 2: Step 3: Re-code verbatims from LLTs recently made non-current Identify new LLTs that are exact matches for verbatims Review the list of changes to identify terms of specific interest Step 4: Decide on any areas of focus 14

15 Remaining Challenges Step 5: Identify previous verbatims that are more appropriate to link to new LLTs Step 6: Step 7: Document decisions Inform colleagues across the organisation 15

16 How to Identify Verbatims? Review all verbatims in dataset, or Identify LLTs of interest and search for verbatims 16

17 Bottom-up or Top-down Approach? 17

18 Impact of Versioning Challenges Benefits 18

19 Versioning Resources Excel list of changes MVAT MSSO Versioning Tool What s New Document What s New Webinar Coding Tool Function 19

20 Discussion What approach do you take for versioning clinical trials? How do you decide which studies to upversion? How do you handle locked studies? When do you implement? Any carry-over activities? What versioning activities do you perform? What resources do you use to support versioning? What documentation do you maintain? How do you communicate changes? Do you implement supplemental terms between versions? What are the challenges you face in versioning? Do you have any tips or solutions to share? 20

21 Thank you