Learning from others

I took a little time today to review some more older warning letters sent to clinical investigators following FDA inspections.  Here's one I came up with that I thought could be worth discussing.

There are numerous violations identified by the FDA inspector in this warning letter, but the two observations I wanted to talk about were:

1) A discrepancy between sources and CRFs.  This goes to show that you cannot take FDA inspections lightly.  There were several situations identified by the inspector where source documentation at the site did not match what was reported in the Case Report Forms.  Yes a monitor should have caught this prior to the inspection, but the site is ultimately responsible for the data.  Furthermore a site may argue that mistakes happen and the data may have gotten somehow transposed, but even small differences between the source and CRF could have significant implications for the data in a trial.  Morale of the story: take your time and be diligent when transcribing data from source to CRF.

  P.S. The FDA inspector also noted that corrections were made after a subject completed a trial without explanation.  It does look suspicious and I can completely agree with the inspector on questioning the legitimacy of the data in that situation.

2) Not properly consenting subjects.  Their were several violations of this genre reported, but one that I would like to point out is as follows: 

 "In a letter dated March 1, 2006, the IRB informed your site that they had approved informed consent form version 021706 which included modifications that were made to the risks section. The IRB’s letter further stated that current and new subjects were to sign the revised informed consent form. There was no documentation found during the FDA inspection to show that your site re-consented Subject #0004, who was still enrolled into the study at the time, with the revised informed consent form to inform them of the possible additional risks the subject may experience."


   This says that the site received notification from the IRB of a amended informed consent and that all currently enrolled subjects (as well as new ones) should sign the amended consent to inform them of newly identified risks of study participation.  For some reason this re-consenting did not happen (whether it was accidental or not is not the point here), and the investigator is the one who takes the heat because the participant was never made aware of new risks that could have affected his/her willingness to continue participating in the trial.  Again, mistakes do happen but the FDA will not take them lightly if the safety of subjects are at stake (if at all).  Morale of this story: take whatever measures are necessary to ensure that the recommendations of the IRB are followed with regards to the consent of subjects participating in clinical trials.




  Notice I did not say that the sponsor has power over the administration of the consent....more on that later...