Terms of Reference, Membership and Report ISCB40 Leuven 2019: AGM Wed 16 July

1. Terms of Reference, Membership and Report ISCB40 Leuven 2019: AGM Wed 16 July ISCB Sub-Committee Statistics in Regulatory Affairs

2. SiRA Sc:Terms of Reference and Membership Footnote: Those in red are new members to the committee since the annual meeting last year.

3. SiRA Sc:Report Footnote: New terms of referencewereapproved by ExCom on Sunday, 14 July 2019. • The ExCom in Melbourne 2018 asked the SC to review the current Terms of Reference and update accordingly with the consideration of the ISCB President’s role of their approval of submission of the opinion of the ISCB members in response to regulatory guidances. the SC reviewed the current Terms of Reference, and have updated as follows in red: • Old terms of reference: The subcommittee on Regulatory Affairs will review, comment upon and seek to influence the development of regulatory requirements, guidelines and other documents concerning the scientific aspects of data generation, collection, management, analysis, and reporting. In general, the subcommittee will seek out and handle all regulatory issues in the name of the Society with the approval of the President or in his/her absence, the Vice‑President. • Suggested new terms of reference: The Subcommittee on Regulatory Affairs will review, comment upon and seek to influencethe development of regulatory requirements, guidelines and other documents by obtaining the recommendations of ISCB members (SiRA process). This primarily concerns the scientific aspects of data generation, collection, management, analysis, and reporting. In general, the subcommittee will seek out and handle all regulatory issues in the name of the Society with the approval of the President or in his/her absence, the Vice‑President. Here the approval refers to the SiRA process for gathering the recommendations of the ISCB members and not the content of those recommendations. • The SC also reviewed the current process for receiving notifications for regulatory guidance updates/request for reviews, as well as alerting the ISCB members of those documents that may not be circulated for comments among the members.

4. SiRA Sc:Report • SiRA Sc discussed and commented on several regulatory guidelines and compilation of ISCB comments on EDA or FDA guidances: • FDA guidance “Meta-Analyses of Randomized Controlled Clinical Trials to Evaluate the Safety of Human Drugs or Biological Products Guidance for Industry” was submitted to the FDA on 07 January 2019 by Nicole Close. • The question about possibility to review EMA guidance “Draft Guidance Consultation: Expansion Cohorts: Use in First-In-Human Clinical Trials to Expedite Development of Oncology Drugs and Biologics Guidance for Industry” by ISCB members was circulated among SiRA SC members on 17 August 2018. The collection of votes was closed on 14 September 2018. 4 members were unsure, 2 members agreed with the circulation, 6 didn’t vote. The request for review was not circulated among ISCB members. • The question about possibility to review EMA concept paper “EMA Consultation: Concept paper on the revision of the guideline on the evaluation of anticancer medicinal products in man” by ISCB members was circulated among SiRA SC members on 11 February 2019. This concept paper started stormy discussion (including about 25 emails with different opinions) spanning almost one month about which guidances should be reviewed by SiRA (other than statistical, disease-related draft guidance, etc.) mentioning also logistical constraints of a SiRA Sc Chairperson (having to handle the collation and consolidation of any guidance, where expertise in a particular therapeutic area) is necessary) and the quantity and quality of the comments ((non)statistical). Neither the request for review or just information were circulated among ISCB members.

5. SiRA Sc:Report • SiRA Sc discussed and commented on several regulatory guidelines and compilation of ISCB comments on EDA or FDA guidances: • The question about possibility to review EMA guidance “EMA Consultation: Role of big data for evaluation and supervision of medicines in the EU” by ISCB members was circulated among SiRA SC members on 19 February 2019. The collection of votes was closed on 25 February 2019. 7 members agreed with the circulation with comments, 5 didn’t vote. The request for review was circulated among ISCB members on 25 February 2019. Nobody commented before deadline 29 March 2019 (closing date for submission to EMA was 19 April 2019). • The question about possibility to review EMA guidance “EMA Consultation: ICH guideline E8 (R1) on general considerations for clinical studies – Step b” by ISCB members was circulated among SiRA SC members on 21 May 2019. 8 members agreed with the circulation with comments, 1 agreed just for circulation informing members about this guidance, 3 didn’t vote. The request for review was circulated among ISCB members on 31 May 2019. Deadline for comments is 15 August 2019 (closing date for submission to EMA is 30 September 2019). • The question about possibility to review EMA guidance “ICH guideline E19 on optimisation of safety data collection (step 2b)” by ISCB members was circulated among SiRA SC members on 31 May 2019. 7 members disagreed with circulation informing members about this guidance, 5 didn’t vote. Neither the request for review or just information were not circulated among ISCB members.

6. SiRA Sc:Report • The Wikipedia Project Poster was presented at the Vigo ISCB conference. A related article was submitted for the mid-year ISCB Newsletter in order to publicise the Wikipedia Project. • The initial “List” (Wiki SiRA List) and “Article” (Wiki SiRA Article) about SiRAguidanceswere drafted by the SiRA Sc and have been implemented in Wikipedia by Juan Torres (2016) and Harbajan Chadha-Boreham (2017-2018), respectively, and partially also by Stanislav Katina (2017). • A related “User Guide” was developed by Harbajan Chadha-Boreham, Juan Torres and Stanislav Katina for the Vigo 2017 presentation. • Following the rejection of SiRA Wikipedia paper by Pharmaceutical Statistics (PSt) journal in November 2017, the Subcommittee decided not to pursue publication in a journal. Instead, it was decided to post the paper on the ISCB Website. • Consequently, the Paper has been revised addressing the PSt reviewers’ comments. As the paper required references to previous Wikipedia Initiative material (Conference Abstracts, Posters and the User Guide), it was necessary to create a specific Wikipedia section on the ISCB SiRA webpage.

7. SiRA Sc:Report • Harbajan Chadha-Boreham collaborated with David Warne for developing the following section on the ISCB SiRA webpage (ISCB SiRA web). • The webpage section contains links to all the key Wikipedia Initiative material, including the related final Paper, as well as links to the SiRA Wikipedia Page (Wiki SiRA Article) andWikipedia List for Regulatory Guidances(Wiki SiRA List). • The above-mentioned material and related weblinks were disseminated to ISCB members via e-mail (Harbajan Chadha-Boreham, 11 March 2018) in order to encourage contributions to the Wikipedia Page and List. • The page was last edited on 03 September 2018. The list was last edited on 25 April 2018, i.e. since dissemination,one person edited both the main Guidance page and the List and two other people edited the Guidance page. • SIRA subcommittee will review the page and list once a year during SiRA subcommittee meeting, identify the topics and updates, and post updates to Wikipedia within 90 days. • SiRA subcommittee is going to disseminate information to other societies and organisations.  • There is also the possibility of student competition idea that Martin Schumacher brought to our attention. Footnote: ISCB members to contribute to Wikipedia SIRA Page and List.  

8. SiRA Sc:Report

9. SiRA Sc:Report