NorthWest Biotherapeutics Inc (NWBO)

[anders2211]

There are plenty of other persons and resources they can turn to for that work.

Then who do you think drafted the amended SAP? Dr Bosch? that would have been a red flag for the FDA. I dont see why Duffy could have not been that person, you dont explain why that would be a problem. He was hired and was an employee of NWBO and could do that job perfectly.

It would be inconceivable to change endpoints after they were unblinded. The FDA clearly states that the investigator identified the primary endpoints when they designed the trial should be removed when the amendment of the trial is drafted.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1852589/

Guiding Principles
The principle consideration when evaluating whether to modify an endpoint is whether the decision is independent of the data obtained from the trial to date. If the decision to revise endpoints is independent of the data from the trial, then such revisions may have merit. In fact, Wittes [8] encourages consideration of changes in long-term trials, as medical knowledge evolves or when assumptions made in design of the trial appear questionable. Wittes further argues that researchers “may consider changes to the primary endpoint when the trial has airtight procedures to guarantee separation of the people involved in making such changes from data that could provide insight into treatment effect” [8].

Some trials have successfully changed endpoints after the trials began by maintaining independence between the decision and the trial data. For example, the randomized Post-CABG (Post Coronary Artery Bypass Graft) trial [9] compared two lipid-lowering regimens in patients who had coronary artery bypass surgery. The investigators explicitly did not identify a primary endpoint when they designed the trial. An angiogram to assess lipid deposition in the coronary arteries was conducted at entry and then again five years later. The researchers planned to compare changes in lipid deposition over the five-year interval between the two regimens. Because by design no endpoint would be available for five years after randomizing the first participant, the protocol team used this period to define the endpoint and to develop methods for analyses. Although the endpoint was not prespecified in the design phase, a practice that is not generally recommended, trial leadership ensured that the selection of the endpoint was independent of data from the trial.

http://www.pharmatimes.com/news/handle_with_care_changing_endpoints_in_clinical_trials_989732

Given this frequency, Evans writes, it is important to determine when changes to endpoints are appropriate and how they should be reported. The main consideration, he says, is whether the decision to modify an endpoint is independent of the data obtained from the trial to date. If this is so, he argues, the revisions may have some merit or even be worth encouraging. If not, then there is a danger of cherrypicking – for example, by selecting new endpoints because they show a trend towards significance and ignoring other candidate endpoints because the trend is not desirable.

Investigators and reviewers should ask three key questions to gauge whether a change in endpoint really is independent of the trial data, Evans suggests: what is the source of the new information that prompts consideration of the change (e.g., results from another trial, which may make the revision credible); whether interim data on the endpoint in question (or related data) have already been reviewed; and, “most importantly”, who is making the decision to revise the endpoint (e.g., the trial sponsors or an independent external advisory committee).