Writing the DSUR: Development Safety Update Reports

After this lecture, you can state the four objectives ICH E2F sets for the DSUR and what each demands of the author; explain why the DSUR is not where safety issues are first detected or notified; and map each objective to the DSUR sections that chiefly serve it.

After this lecture, you can distinguish the DSUR from expedited reports, the Investigator's Brochure, the PBRER and the RMP; state three practical consequences of those differences; and list five things the DSUR is not.

After this lecture, you can name the readers of a DSUR and what each takes from it; list the five things a good DSUR does; and say which sections carry the report at each stage of a program's life.

After this lecture, you can recognize the five failure modes in a weak Section 18 paragraph; list the questions a regulator would ask about such a paragraph; and take the four things you need from last year's DSUR without copying it.

After this lecture, you can set the DIBD, reporting period, data lock point and submission deadline for a program; explain when and how a DSUR may be aligned with the PBRER on the IBD; and apply three rules that prevent most dating errors.

After this lecture, you can decide whether a program needs one DSUR or several and justify it in Section 1; apply the E2F options for fixed combinations and multi-drug regimens; and write Section 1 wording that names scope, reason and what cannot be concluded.

After this lecture, you can sort data sources into always in, in if relevant, and out with an explanation; complete a one-page scope record; and handle scope changes during the year without moving the DIBD.

After this lecture, you can state what E2F expects about blinded and unblinded data in the DSUR; set up two report versions and a distribution list that protect a trial's blind; and recognize the five common scope failures.

After this lecture, you can state the three process requirements E2F sets; build a back-planned DSUR timeline from any data lock point; and explain why the key messages review is the most valuable milestone.

After this lecture, you can assign DSUR responsibilities with a RACI matrix; explain why the judgment in Sections 18 and 19 cannot be delegated; and write an output specification that delivers the right table the first time.

After this lecture, you can explain why serial review loops and how a consolidated review converges; set an owner and cut-off for late-breaking information; and keep sponsor ownership when vendors and partners contribute.

After this lecture, you can run a DSUR kickoff that settles every decision possible before the data exist; name the records to keep all year and what each feeds; and recognize the five common process failures.

After this lecture, you can identify the reference safety information that governs a reporting period; explain why E2F fixes the RSI at the start of the period; and state the five rules that follow from E2F §2.6 and the guidance for Sections 4 and 7.1.

After this lecture, you can handle an IB revised during the period without mixing standards of expectedness; write a Section 4 entry that reports a significant change and points to the evidence; and decide when more than one reference document is justified, and how to name each.

After this lecture, you can reconcile the SUSARs expedited in the period with the interval line listing; classify each mismatch as legitimate, an output error or a reporting failure; and decide how a genuine reporting failure is handled in the DSUR and the quality system.

After this lecture, you can recognize the five features of a usable RSI section in the IB; draft Section 7.1 wording for the four common situations; and spot the five common RSI failures in a draft DSUR.

After this lecture, you can explain why exposure is the most important number in the DSUR; assign each trial the correct E2F status, completed or ongoing; and build a Section 5 inventory that does not double-count extension subjects.

After this lecture, you can estimate exposure by arm in a blinded trial from its randomization ratio; combine actual and estimated counts in one table, flagging each source; and write a method paragraph that states the rationale and the limits.

After this lecture, you can choose between subject counts and subject-time, and present both where needed; calculate rates per 100 subject-years and explain what they show; and present exposure for large healthy populations, tiny denominators and long-marketed drugs.

After this lecture, you can present exposure split by trial, dose and age so every SAE column has a denominator; write a specific statement when exposure data are incomplete; and write one exposure sentence and keep it from drifting across the report.

After this lecture, you can explain why listings show interval reactions and tabulations show cumulative events; apply E2F's rules on blinded data, seriousness terms and exclusions; and say which DSUR sections are interval, cumulative or both.

After this lecture, you can specify the fields of an interval SAR line listing and what reviewers check in each; apply the three listing rules that cause most errors; and write a Section 7.2 case selection statement.

After this lecture, you can design tabulation columns that follow the questions Section 18 will ask; decide whether to include or exclude an event, and write the footnote; and reconcile the clinical and safety databases before the tables lock.

After this lecture, you can present adverse events of special interest and a deaths list beside the standard tables; run a ten-point self-check on listings and tabulations the day they arrive; and decide whether to pool or split a tabulation, using XB-7 as the model.

After this lecture, you can state what each of Sections 9 to 15 covers under E2F §3.9 to §3.15; explain why these sections report and Section 18 interprets; and set up a source intake log that routes every outside item to its section.

After this lecture, you can write findings-based entries for Sections 9 to 13 using the book's models; decide when an efficacy finding belongs in Section 15; and specify what a data exchange agreement must cover and design a literature search that holds up.

After this lecture, you can trace a class finding from Section 13 through Sections 18.1, 19, 3 and 20; make and record a decision on a class finding: add, monitor or explain; and write a Section 14 summary of another DSUR that compares conclusions.

After this lecture, you can apply the significance test to decide whether an action belongs in Section 3; route an event to Section 3, Section 4, both, or neither; and write a Section 3 entry that answers the six questions.

After this lecture, you can maintain Appendix 2 as a cumulative record, including closed requests; report urgent safety measures, holds and updates to earlier actions; and build a Section 3 table that links market and trial actions for a marketed drug.

After this lecture, you can decide whether a post-lock finding clears the bar for Section 17; set a cut-off and carry each Section 17 item into Sections 18 to 20; and report investigator and ethics committee communications in Section 3.

After this lecture, you can place each trial in the right Section 8 subsection using E2F's definition of completed; classify a finding as new, confirmatory, refuting or not informative; and use the category to decide a finding's length and where else it must appear.

After this lecture, you can reduce a clinical study report to a Section 8.1 paragraph of findings; write Section 8.2 for a blinded trial without saying more than the data allow; and report long-term follow-up with subject-time, including the absence of delayed events.

After this lecture, you can trace a refuting finding through Sections 8, 18, 19, 3 and 20; report named-patient and expanded access experience with its limits stated; and decide how much efficacy belongs in Section 8 and where it flows.