A loss of more than 10% body weight within a week was decided as ethical endpoint.
Although strictly speaking not required for an approach in which chimeras serve as an endpoint, we decided to maintain this quality control as a means to identify ESC clones with impaired germline-competence caused by loss of pluripotency or the acquisition of genetic defects during culture and manipulation.
There are many challenges with proving effectiveness and efficiency of educational measures, such as simulation, e.g. to decide on endpoints [ 14], to validate instruments [ 15], and to design good studies (that avoid measuring enthusiasm and biases).
The outcome on the primary endpoint was decided on a two-sided significance level of 0.05.
For the purpose of our research we decided to use as endpoint a Fib-4 value >1.45, based on literature data showing that a threshold value <1.45 has a negative predictive value for the exclusion of extensive fibrosis (F4-F6 of the Ishak classification) of 90%, and a threshold value >3.25 has a positive predictive value for the diagnosis of extended fibrosis of 65% [ 14, 15].
We decided to use a composite endpoint consisting of immediate and delayed recall from the 10 word memory list and the CDR, as we believe that the first instrument will be able to capture differences between cognitively well functioning participants, and the latter one differences in the lower part of the functional spectrum.
Given the time and costs of clonal sequencing for each partner in those first 58 transmission pairs, the trial endpoint committee decided to utilize consensus sequencing of partial env and gag regions to increase efficiency in determining transmission linkage.
Instead of culling recipient mice at 20% of bodyweight loss, we decided to set the endpoint at 25% weight loss.
This is a high-risk assessment, as they could have also decided to move the endpoints because the efficacy that they were beginning to see put the trial at risk.
The endpoints were decided prior to study commencement.
63 Since mortality is not a feasible endpoint in a single-centre trial, we decided to use sequential organ failure assessment (SOFA) score as a surrogate primary outcome measure.
