That was the rallying cry from both investigators and patients at a public meeting on ICH E8 R1, General Considerations for Clinical Studies, held at FDA yesterday.

I joined a Webex of the proceedings at different points during the day. The changes to the guideline are significant. It promotes fit for purpose clinical trials by spelling out the ‘Quality by Design’ concept and identifying ‘Critical to Quality’ factors.

The three take-aways for me were:

1. Stakeholder engagement. Dr. Buse, Division Chief and Director of the Diabetes Center at UNC, said clinician input is essential and that language in guidance should be more forceful. Sponsors should ‘pare down’ the burden they put on patients. John Adams, Best Medicines Coalition of Canada, said patients want to be at the table. They are not subjects, but participants or partners. ‘But are we junior partners or equal partners?’ ‘Patients should be treated with respect and there should be a duty to report back to patients and let them know the study results, good or bad.’ ‘Nothing about us without us’! A principal investigator in the audience made the same comment.

2. Quality by Design. As per Fergus Sweeney, Chair of the ICH Working Group, this is about ‘doing things differently-change- don’t just add more to the status quo’ and that change management will be the greatest challenge when it comes to implementation. Several speakers expressed concern that the guidance would be a seen as an added layer of regulation and that if processes are not well-defined regulators may ‘over-interpret’ the guidance. However, Dr. Leonard Lichtenfeld, Chief Medical Officer at the American Cancer Society, said the data collected should be relevant to the scientific question asked and should not be collected for the sake of additional data. He also advocated for the inclusion of elderly people in studies. ‘Cancer is a disease of elderly folk’ and spoke of an instance where Medicare would not cover a procedure because benefit has only been shown in a younger population. He was one of several speakers who called for the inclusion/exclusion criteria of studies to be revisited…that many trials do not actually fit the needs of patients. A representative of the Pancreatic Cancer Action network told us only 4% of patients with pancreatic cancer qualify for a trial. A speaker in the audience, a clinician, encouraged people to ask companies to explain the rationale for an exclusion criterion. He spoke about being in the position of having competing studies to offer his patients but has no way to judge the quality of a trial design. Does he offer all to his patients and let them decide or does he just offer the trial which is having a tough time recruiting patients?

3. Critical to Quality Factors. As per a statistician on the panel there are three types of threat to quality: threats stemming from bias…. which always must be taken of the table, threats stemming from a lack of precision, and threats related to generalizability. She believed the guidance does not yet have enough clarity and conciseness. A Merck representative liked that CTQ factors were linked to proportionality. Precision is extremely important in a rare disease trial in a very small population but not critical in 3000 patient study of cardiovascular outcomes. He asked for more examples in the guidance document to help with implementation.

One other comment that struck home for me was about Real-World Evidence (RWE). Not sure who made the comment, but it was a panel member. ‘RWE is not as good as you might think even if it is electronic data…it has to be validated and it has to be accurate’. His medical record has listed both his marital status and religion incorrectly and he has not been able to get it corrected!