9 For each trial, we reviewed the protocol, statistical appendices, amendments, and publications that reported the primary outcome measures.
We added the following elements to our extraction sheets: date of participant enrolment, unblinding of the trial, protocol for which we had the full text, protocol amendments, statistical analysis plan for which we have the full text (and its amendments), patient consent form, randomisation list and certificate of analysis.
The numerous appendices (section 16 of ICH E3) contain important online supplementary data needed to understand and interpret the trial, its context and history. 1 2 These appendices include such documents as the trial protocol, protocol amendments, statistical analysis plan, blank case report forms, certificates of analysis, randomisation lists and consent forms.
For most of the clinical study reports we requested, EMA had the protocol, protocol amendments, statistical analysis plan, blank case report forms and other appendices contained in what Roche terms the second 'module' of a full clinical study report (see online supplementary appendix 1).
The validation of the main results of a confirmatory clinical trial requires not only access to patient-level data, but also access to the clinical trial protocols (including amendments), statistical analysis plans together with software code, data dictionaries and the study reports.
In this regard, the plant traits like the root length and the leaf area/hill showed a significant statistical difference among the amendments and between two active growth stages (panicle initiation and flowering), while no such differences among amendments and the two active growth stages occurred with respect to soil attributes like soil pH, soil organic matter and soil electric conductance.
Appendices provided descriptions of the outcome measurement tools used, individual patient outcomes, compliance, case report forms, detailed statistical analyses, and protocol amendments.
A statistical method resulting in an amendment of statistical parameters is proposed.
These findings led to the amendment of the statistical analysis plan of the HERALD study to state that HRG would be the primary predictive biomarker for the study and to specify that PFS in this single subgroup would be evaluated irrespective of the outcome in the ITT population.
The size (page length) reflects the level of detail as well as the presence of many elements such as protocols and their amendments, randomisation lists, statistical analysis plans, certificates of analysis and extra data on subpopulations.
