Adverse Events Subteam

Membership

• Stephine Keeton (co-lead) - PPD
• Janelle Charles (co-lead) - CDER
• Fabrice Bancken - Novartis
• Navdeep Boparai - Spcorp
• Andreas Brueckner - Bayer Healthcare
• Suzanne Demko - CDER
• Larry Gould Merck
• Liping Huang - Roche
• Qi Jiang - Amgen
• Mat Soukup - CDER
• Jeff Summers - CDER
• Yaning Wang - CDER
• Kenneth Koury - Spcorp

Developments

• AE Graphs

Conference Template

• Conference Abstract
• Conference Slides

Subteam Minutes

20April2011

Adverse Events Subgroup

Academia/FDA/Industry Safety Graphics Working Group

________________________________________________________________________

• Discussion of graphs
• Open discussion

• The subgroup continued the discussion of graphs. Members provided comments on ways to improve the recommended graphs.
• Members needed clarity on some graphs that were somewhat difficult to interpret.

• Stephine and Janelle will continue compiling the final AE graphics document of recommended graphs.
• Janelle will talk to Andreas about providin the subgroup with description of the graphs he created at the May meeting.
• Qi will email Janelle her edits to be added to the graphical document.
• All subgroup members will provide suggestions for the final display page for the AE section of the Wiki. Mat will lead the discussion at the May meeting.

25March2011

Adverse Events Subgroup

Academia/FDA/Industry Safety Graphics Working Group

________________________________________________________________________

• Discussion of graphs
• Open discussion

• The subgroup continued the discussion of graphs. A number of graphs were identified as recommended graphs for displaying AE data. Members provided comments on ways to improve the recommended graphs.
• Mat agreed to incorporate suggestions for modifications of the graphs that he created. He will share modifications with the subgroup.
• There was discussion surrounding stacked bar charts and the suitability of these charts for qualitative rather than quantitative data representation. Stephine and Janelle will get clinical input on the sample graph discussed.

• Stephine and Janelle will continue compiling the final AE graphics document of recommended graphs.
• It is anticipated that in April's 1.5 hour meeting the subgroup will complete discussion of all graphs. Then the subgroup will begin to provide comments for the final graphical document.

24February2011

Adverse Events Subgroup

Academia/FDA/Industry Safety Graphics Working Group

________________________________________________________________________

• Discussion of graphs
• Open discussion

• Andreas presented graphs that addressed some of the clinical questions. Recommendations were provided for improving the content of the graphs.

• Stephine and Janelle started compiling the final AE graphics document. After each meeting, we will incorporate graphs reviewed by the team. We will create a final graphics document based on selected graphs from those submitted. The document will then be posted on the wiki for review by the general group.
• The team agreed to extend the next couple of subgroup meetings to 1.5 hours for March and April.
• Subgroups members will continue to discuss graphs for the remaining sectins of the clinical questions document.

21January2011

Adverse Events Subgroup

Academia/FDA/Industry Safety Graphics Working Group

________________________________________________________________________

• Final adverse event document
• Next steps

• Stephine and Janelle will create a document for the final Adverse Events safety graphics. The tentative timeframe for document completion is 2 - 3 months. There will be ongoing review of the document by the subgroup. Once complete, the document will be shared with the general group. Next steps
• Subgroups members will discuss graphs for section III, IV and V of the clinical questions document.

18November2010

Adverse Events Subgroup

Academia/FDA/Industry Safety Graphics Working Group

________________________________________________________________________

• Next steps and other items
• Discussion of graphs
• Action items

• The next Adverse Event Subteam meeting will take place in mid January. The group was reminded to start compiling graphs for sections 3 and 4 of the clinical questions document. Stephine will send the group an email reminder and solicit volunteers.
• Liping reconfirmed that she will present on behalf of the Adverse Events Subteam at the ICSA 2011 meeting in New York.

• Qi presented graphs that addressed some of the clinical questions. Recommendations were provided for improving the content of the graphs. For example, the group recommended that forest plots include treatment effect estimates (relative risk, odds ratio, risk difference and confidence intervals).
• The group discussed ways to use volcano and forest plots as supplements of each other.
• Discussion of graphs will continue at the next meeting.
• The group discussed methods of analyzing adverse events categorized by SOCs when the preferred terms map to multiple SOCs. Specifically, whether the primary or secondary MedDRA path should be used.

• Qi will incorporate suggestions made by group into her graphs.
• Stephine will include steps for browsing the wiki in the next subteam meeting announcement. She will talk to Mat or Mary about deleting attachments.

14October2010

Adverse Events Subgroup

Academia/FDA/Industry Safety Graphics Working Group

________________________________________________________________________

• Discussion of graphs
• Action items

• Liping and Qi presented graphs that addressed some of the clinical questions. Recommendations were provided for improving the content of the graphs. For example, some graphs included p-values for differences across all AEs of interest between treatment groups. The point was made that a p-value may not be the most appropriate statistic for identifying significant differences. Also, if p-values are to be included in plots, then it may more meaningful to only present p-values that represent a safety signal needing further investigation.
• Subteam members were encouraged to keep in mind the take-home message that the graph is meant to portray. The graphical displays should be appropriate for answering a particular clinical question. It was suggested that members first determine the clinical question and then find the best suited graph for that question.
• Graphs are meant to be alternatives to tabular displays of AE data. If the graph is too cluttered with information, then not only is the main message lost but a table may do just as well.
• Members were reminded that the graphical submisions should contain,at minimum, a brief description and the clinical question the graph is intended to answer. The description should be enough so that a reader has an idea of the graphical content.
• While discussing graphs, the issue was raised that not all members had the latest version of word (.docx). A suggestion was made that members submit graphs to the Wiki in simplest versions of word (.doc), pdf or power point.
• Discussion of graphs will continue at the next meetings.

• Qi will incorporate suggestions made by group into her graphs and upload her graphs to the Wiki in pdf form.

14September2010

Adverse Events Subgroup

Academia/FDA/Industry Safety Graphics Working Group

________________________________________________________________________

• Discuss conference slide template
• Discuss of next steps
• Action items

• Liping, Stephine, and Janelle met to update the slide set based on suggestions from the group at our last subgroup meeting.
• Recommendations were made to the slide template. It was suggested to include a table as an example, in the introduction, of complex AE data as a motivation for using graphical display. We agreed that the final conclusions in the presentation should be supported by the content presented.
• While discussing the slide template, a question was raised about developing additional conference templates that will be used at conferences such as the proposed sessions for JSM 2011. It was pointed out that the current slide template was designed for those sessions where presentations will be given by each subgroup, such as the ICSA 2011 accepted session. Janelle agreed to suggest to Bruce that this topic be discussed at the next general meeting.

• We agreed that the next 2 to 3 meetings will be devoted to discussing graphs for particular sections of the clinical questions document.

• Stephine would upload the finalized conference template to the Wiki.
• Subgroup members will volunteer to submit graphs to the Wiki for discussion at the next subgroup meeting.
• Janelle will email Bruce to add discussion of conference sessions to the agenda.

16August2010

Adverse Events Subgroup

Academia/FDA/Industry Safety Graphics Working Group

________________________________________________________________________

• Updates from previous meeting
• Discuss conference slide templates and abstract
• Action items

• Janelle reported that the patient profile plots were discussed at the general meeting. Although sponsors are not required to submit these plots, they are encouraged to submit the variables so that such plots can be created by the Agency. Dr. Rochester suggested that it is a good idea to include these plots on the Wiki to address clinical questions related to adverse events.

• Andreas, Liping, Qi, and Ken met to discuss and develop draft conference slide templates and abstract. Overall, the subteam was in agreement with the draft abstract with a few minor edits. Larry made the suggested changes to the document. The subteam decided to share the abstract with the general working group at the next meeting.
• Recommendations were made to the slide template. Formatting issues were discussed to maximize the presentation of information on each slide. In terms on content, it was suggested that the objectives and motivation specifically target the contributions of the Adverse Event subteam.
• Larry volunteered to assist with the slide template development. He will upload guidelines for slides to the Wiki.
• Liping will be the representative for the AE subteam at the ICSA 2011 conference.

• Stephine and Janelle will create a link on the Wiki to upload all graphs in one location.
• Liping, Qi, Ken, Larry and Andreas will meet amongst themselves to update conference slide template prior to the next AE meeting.

23July2010

Adverse Events Subgroup

Academia/FDA/Industry Safety Graphics Working Group

________________________________________________________________________

• We have a new member, Kenneth Koury
• Updates from previous meeting
• Discuss conference templates, clinical questions, and graphs
• Action items

• Stephine reported that she took Adobe Acrobat Connect Pro training. This will be a useful tool for conducting and sharing files for future meetings. There is no cost associated with the software but users must have Flash Player and internet access.
• Liping has not received any suggestions for additional variables to include in the Roche dataset.

• In the last meeting, Andreas and Liping volunteered to take the lead for developing a template for conference abstract and slides. Ken and Qi have agreed to assist. They will report to the subteam on progress made at the August meeting. *The subteam agreed that the clinical questions document will be uploaded to the wiki incorporating changes discussed during the meeting.
• The team continued discussing the submitted graphs. Members were encouraged to submit all graphs to the wiki using the general principles subteam template. The subteam discussed whether plots at the patient level were within the scope of the working group.

• Stephine will upload the clinical questions document to the wiki. She will also create links based on the categories from the document. The members will use these links to submit the graphs.
• Liping, Qi, Ken and Andreas will meet amongst themselves to work on conference template prior to the next AE meeting.

4June2010

Adverse Events Subgroup

Academia/FDA/Industry Safety Graphics Working Group

________________________________________________________________________

• We have a new member, Andreas Brueckner
• Updates from previous meeting
• Discuss datasets, clinical questions, and graphs
• Action items

• Mat met with Brenda and Greg regarding the use of the first CDISC pilot data. He mentioned that access to the data by non-CDISC members, can be problematic.
• Qi may be able to share the SOLVD datasets with the subgroup if the subgroup would like. She noted that the SOLVD datasets are quite old and are not in the CDISC format.
• Liping was able to obtain a dataset from Roche for an already marketed product containing 1146 de-identified patient records. The data is composed of two datasets – demographic data and AE data. The dataset is not in CDISC but in a standard data format.
• Stephine reported that Adobe Acrobat Connect Professional is a tool to facilitate our graphics teleconferences. Stephine will follow-up in the next meeting and provide information about software costs.
• Liping and Andreas volunteered to develop template slides and abstracts for the subgroup for upcoming conferences.

• Liping submitted a document of variables included in the Roche dataset for comments. *The clinical questions document was approved by the team. Liping suggested categorizing clinical questions, for example with headings ‘Frequency of AEs’, ‘Time to Event’, etc.
• The team discussed some of the submitted graphs. A consensus was to include interpretations and limitations of each graph submitted in the future.

• Stephine will follow-up on the Adobe Acrobat Connect Pro.
• Mat will report on access to CDISC pilot data.
• Liping will create categories for the clinical questions.
• Janelle will forward the updated clinical questions document.

13May2010

Adverse Events Subgroup

Academia/FDA/Industry Safety Graphics Working Group

________________________________________________________________________

• Updates from previous meeting
• Discuss clinical questions
• Timelines and action items

• Mat checked on the use of a CDISC pilot dataset. He mentioned that access to the data by non-CDISC members, can be problematic.
• Qi may be able to share the SOLVD datasets with the subgroup if the subgroup would like. She noted that the SOLVD datasets are quite old and are not in the CDISC format. A possible fix is to simulate a dataset using preferred terms from the MedDRA library.
• Liping reported that there is no problem for the AE subgroup to use data from Roche for already marketed products.
• Qi suggested getting a dataset from NIH called SOLVD (Studies of Left Ventricular Dysfunction) which has safety information. This dataset may be used as a backup or in conjunction with the dataset from Liping’s dataset.

• A document containing all clinical questions was sent to the group for discussion. *One topic under discussion was how should we define the adverse events since different definitions from various entities can skew results. The consensus by the group is definition of AE’s is beyond the scope of the group and the graphics are applicable regardless of the definition of pre-specified AE.
• The group observed that there was overlap among the questions and some reductions (and editing) were necessary.

• One possible suggestion was to have a final clinical question draft to the general group in July 2010 and completed graphics document by early or late fall.
• Further input is needed from the general group with regards to overall deadlines for the final AE subgroup document.

• Janelle will organize and lead the next AE subgroup meeting.
• Mat will ask Mary Banach to attend a general meeting to demonstrate the Wiki.
• Stephine and Janelle will condense the list of clinical questions and send the group for any additional comments.
• Stephine will check into the possibility of having a “live meeting”.

15April2010

Adverse Events Subgroup

Academia/FDA/Industry Safety Graphics Working Group

________________________________________________________________________

• Introductions
• Clarify the goals and objectives of the subgroup
• Determine clinical questions and involvement
• Identify tasks and timelines
• Discuss next steps
• Frequency of meetings

• Collection and review of sample graphics, based on clinical questions to be answered
• Identify recommended graphics to answer the questions
• Description of how to interpret each graph
• Store code, graphs, descriptions and data templates

• The first step for the team is to create a document that contains the clinical questions that the graphs will answer.
• The team will submit questions via email to Stephine by April 29th.
• After the clinical questions are determined, the group will focus on generating graphs to answer the questions. If necessary, the group can revisit the questions and graphs in an iterative process.

• Mat suggested the Duke data repository as a source for information on adverse events. Mat is also looking into a CDISC pilot submission/dataset that may be appropriate and accessible by the group. Mat will inform the group on the status of obtaining CDISC datasets.
• Qi (Amgen) and Liping (Roche) will also check with their respective companies for datasets that may be contributed to the subgroup.

• The secondary goal of the group is developing the code for the graphics. The primary focus of the subgroup is developing the clinical questions and graphs to answer the questions.
• Mat suggested that each subgroup may define a workspace and set up a wiki to upload graphs that are assessable to the group. Mat will meet with the wiki group and provide updates to the group.

• The team should submit clinical questions via email to Stephine by April 29th.
• During the development of the clinical questions, the team can begin to compile graphs to include into the AE subgroup document.
• Once the document is near completion we plan to give a brief presentation to the entire working group.

Attachments 2Attachments 2

Topic attachments

I	Attachment	Action	Size	Date	Who	Comment
pdf	AE_Group_discussion.pdf	manage	4 MB	10 Feb 2011 - 11:10	UnknownUser	57 graphs ordered by clinical question
doc	Adverse_Event_Clinical_question_categories.doc	manage	41 K	28 Jul 2010 - 13:09	UnknownUser