Nearly 60 percent of all protocols used in clinical trials for new drugs are amended during the trial, but one-third of those changes could have been avoided and saved countless dollars, according to an analysis by the Tufts Center for the Study of Drug Development.
Specifically, the review found that completed protocols across all clinical trials incurred an average of 2.3 amendments, and each required an average of 6.9 changes to the protocol. And the high rate of amendments is likely to persist, since the analysis found that the mean number of amendments was both positively and significantly correlated with a rising number of procedures per protocol, study length, and number of investigative sites participating in each trial.
The analysis also found that, across all phases of clinical trials, 43 percent of amendments occur before first patients are enrolled, with amendments more likely to occur in Phase I studies. And more than half of all protocols require one or more amendments, with the higher number occurring during Phase III, at 8.5. Also, one-third of all amendments involve protocol description and patient eligibility criteria, and the median total cycle time to identify and resolve a protocol problem is 61 days.
In commenting on the findings, Ken Getz, who is a senior research fellow at Tufts CSDD and runs the CenterWatch clinical trial resource, says in a statement that amending protocols is sometimes necessary, but drugmakers and clinical research organizations may be able to minimize changes and, therefore, save money by improving study design and patient recruitment.
6 Comments
This does not surprise me at all. Nowadays, the people writing the protocols are often people with no practical clinical experience or, if they have a clinical background, are people who've never been responsible for handling day-to-day ops of running them. Back in the old days, the more senior CRAs/study managers/directors who had substantive study coordination/monitoring experience were heavily involved in the study design and writing of the protocol (as well as CRF design) - this made a huge impact on the ability to operationalize the study appropriate because they were are of who the real end user of the protocol is. Clinical development jobs (and minimum experience for those jobs) have been split up and dumbed down so much that protocols in general are poorly written and poorly executed/managed because of this and the fact the study is treated like some sort of assembly line. Process engineering/re-engineers has ben applied to this part of the industry by people who obviously have little understanding of what is actually necessary for a clinical trial, aided by people prematurely promoted (many of whom who are blissfuly unaware of their lack of depth and breadth of experience) in the most destructive of ways.
Yeah, that's the attitude today, develop a drug as you build a car, outsource the motor here and the electronics there and finally nothing works, as a drug is not a machine...
Agree with above. To follow on cranky's comments, the vast majority of changes to a protocol do not require an amendment, and can be done by what is usually termed an administrative change. You only need an amendment with major changes, such as a change in the number of study subjects, or any procedural change that might increase risk to the subject
Way to many amendments clogging up the IRB approval process that could have been done as admin. changes.
I agree with olcranky clinical research is not what it was a decade or so ago when we had experienced trialist involved in writing protocols. Having been in this industry since the late 80s, even the medical directors writing some protocols don't have the requisite experience. It is amazing their lack of cliical trial experience. Remember all the layoffs, many were experienced trialists that have now moved on to other jobs.
ex CRO exec, I agree with you. Also a dearth of experienced trialists at the sponsor and CRO level means that their is no voice of reason every time someone has a brilliant idea to do a protocol amendment.
I actually had an idea that worked to tamp down this activity. I wrote a clinical trial SOP which dictated that every third amendment triggered a complete rewrite of the protocol, , instead of stuffing all of the amendments in the original protocol like circulars in a grocery store shopping bag. Since most people hate the idea of complete protocol rewrites this method actually worked to reduce the number of extraneous amendments.
As someone who works at a Phase 1 clinical research center as a coordinator, I have experienced first hand the lack of feasible thought put into a lot of protocols. For example, the subject has to be supine for 15 minutes prior to vitals but at the same time they must also have blood drawn and clean-catch urine collected. Or the procedures don't match the T&E table and there is back and forth discussion before FPE. It is the fundamentals such as this that had been lost in protocol writing. Maybe if the pharma companies had someone on the protocol writing team to review protocols for things such as this, then the money they saved in ammendments and protocol re-writes could put another unemployed person to work.