F1K-MC-EVDP Statistical Analysis PlanPage 1
7.Unblinding Plan
Final Analysis
The study contains 3 periods: the primary 28-day follow-up period and secondary follow-up periods at 90 days and 180 days. A separate datalock will occur for each period (the 28-day, 90-day, and 180-day datalocks). Each datalock will occur after all patients have completed the relevant study period and data are determined to be complete. Approval for each datalock will be given by the co-chairs of the Academic Steering Committee. Activities related to data set creation and programming specifications for the data displays for all study periods will be completed before the 28-day datalock. After the 28-day datalock, a clinical study report of predefined 28-day data will be prepared for regulatory submission. After the 180-day datalock, a 180-day study report of the 90-day, 180-day, and the remaining 28-day data will be prepared.
Several groups are involved in the conduct of the study: an Academic Steering Committee (some of whom are also investigators in the study), an academic research organization (ARO; Duke Clinical Research Institute), a contract research organization (CRO; Parexel), and the sponsor (Eli Lilly and Company [Lilly]).
28-Day Datalock
The responsibilities and personnel unblinded in each group involved in the conduct of the study are as follows:
Academic Steering Committee. The Academic Steering Committee members will be responsible for writing the primary manuscript for the study. Academic Steering Committee members who are site principal investigators and any other site principal investigators who are unblinded to patient-level data to prepare the primary manuscript will not be involved in the collection of clinical data for patients who have not yet completed the 90- and 180-day follow-up periods, but will instead ensure that a subinvestigator is available to complete these functions. The Academic Steering Committee co-chairs will keep a running log of committee members and investigators who are unblinded and the date and level of unblinding[1].
Academic Research Organization. The ARO will be involved in the review of data and will produce data displays for the Academic Steering Committee. The personnel to be unblinded include the physician and a limited number of statisticians and statistical analysts. An ARO statistician will keep a running log of all ARO personnel who are unblinded and the date and level of unblinding
Clinical Research Organization. CRO personnel will be responsible for producing the data displays for the 28-day study report. The unblinded sponsor statistician will be responsible for authorizing CRO personnel access to unblinded data. A CRO project statistician (the unblinded CRO statistician) and at least 2 statistical analysts will be unblinded to patient-level data. The unblinded CRO statistician will keep a running log of all CRO personnel who are unblinded and the date and level of unblinding. The unblinded CRO statistician and statistical analysts will have no further role in the programming of the 90-day and 180-day analysis data sets and data displays after becoming unblinded.
Sponsor. Sponsor personnel will be responsible for writing the 28-day study report for regulatory agencies, which will be provided to the Academic Steering Committee for review and will be approved by the co-chairs. The following personnel will be unblinded to patient-level data to write the 28-day clinical study report and to prepare the submission to regulatory agencies: a project statistician (the unblinded sponsor statistician), clinical research physician, safety physician, medical director, scientific communications associate, regulatory scientists, regulatory associates, global product safety personnel, and personnel who perform peer and quality reviews. Additional personnel may be unblinded as necessary. In addition, personnel may be unblinded to group-level data to prepare the public disclosure of the study results. The unblinded sponsor statistician will maintain a running log of personnel who have been unblinded, the date of unblinding, and the level of unblinding (group- or patient-level). Once unblinded to patient-level data, these personnel will have no further active role in the collection of outstanding 90- and 180-day clinical data. The unblinded sponsor statistician, statistical analysts, and other unblinded personnel will have no further role in the programming of the 90-day and 180-day analysis data sets and data displays after becoming unblinded. The sponsor will maintain a master list of all people, both Lilly and non-Lilly, who are unblinded.
Blinded Personnel. All those unblinded to patient-level data will have nofurther role in collecting outstanding 90- and 180-day clinical data or in making decisions on data handling. A qualified person will be appointed to perform the role of clinical research physician related to the collection of outstanding 90- and 180-day clinical data; this person will remain blinded to patient-level data through the completion of the 180-day follow-up and datalock. All personnel involved in collecting 90- and 180-day data will remain blinded to all patient-level data through the 180-day datalock. Unblinded 90-day data will not be analyzed or disclosed until after the 90-day datalock and 180-day data will not be analyzed or disclosed until after the 180-day datalock.
90- and 180-Day Datalocks
The 90-and 180-day datalocks will occur after all patients have completed the relevant study period and data are determined to be complete. The ARO and CRO will produce data displays of 90- and 180-day data, which will be made available to the Academic Steering Committee and the sponsor. It is anticipated that, other than personnel unblinded at the 28-day datalock, no additional personnel will be unblinded to patient-level data for thesedatalocks; however, if any person needs to be unblinded, it will be documented in the running log kept by the unblinded Lilly, CRO, or ARO statistician, as appropriate. The database will be locked once 28-day mortality status is available for all patients. Mortality at 28 days, the primary study endpoint, will be reported to regulatory agencies prior to submitting a manuscript for publication. The primary publication will be submitted following the 90-day datalock and will report both 28-day and 90-day mortality. Any data inconsistencies that become apparent between the 28-day and 90-day datalocks will be reported in the primary publication.
Blinded Personnel. After the primary data disclosure, all personnel will be unblinded to group-level data; however, all personnel with 90- and 180- day data collection and data management responsibilities will continue to be blinded to patient-level data. After the 180-day datalock, all personnel may be unblinded to patient-level data.
LY203638Approved: 03May 2011
[1] Levels of unblinding are patient level and group level. Patient-level unblinding is defined as unblinded to individual patient treatment assignments. Group-level unblinding is defined as unblinded to aggregate treatment assignments at the treatment group level without knowledge of individual treatment assignments.