US FDA and Research Regulations
Grattan Woodson, M.D., and everyone employed at the Atlanta Research Center, LLC pledge to follow all pertinent US FDA good clinical practice regulations in every respect. The only exception to this policy is when doing so might adversely affect the health and safety of a subject in a clinical trial or one of the ARC staff members.
It is our usual practice to use a central IRB for all research studies conducted here. Over the years, we have had the pleasure of working with Western IRB, Schulman IRB, Copernicus IRB, and many others. ARC personnel are aware of our responsibility to the study IRB and the critical role it plays protecting the interests of the subject participating in the clinical trial.
When a subject presents to our office for screening, our first task is administering the latest IRB approved ICD before any procedure is performed. We take pride in administering the ICD. We give the subject all the time they need to read the document and encourage them to write notes in the margins of the page as they read so they will not forget any questions that arise. In our experience when subjects are truly informed about the purpose, procedures, potential harms of the study and alternative treatments for the study condition they are more compliant with study procedures and are more likely to complete the trial.
The PI is responsible for training all ARC study staff on the protocol is tasked with answering the potential subject’s questions first. If she is unable to do so, she tells the subject so and refers the subject to the PI. If the PI is unable to answer the question we tell the subject we will find out and let her or him know when we do.
At that point, the subject if satisfied with his or her understanding of the ICD and is willing to participate in the study, they sign the document and initial each page. The PI also signs the ICD. Some IRBs require the subject’s signature to be witnessed while others do not. It is our practice to make a copy of the signed ICD and give it to the subject before the leave the screening visit.
When we become aware of the subject experiencing an SAE we act immediately to gather as much pertinent information as we can and notify the IRB in writing within 24 hours. We stay in touch with our sources of information on the subject’s condition and make frequent interim reports as clinically indicated until resolution of the SAE.
We understand our responsibility to submit all study promotional material to the sponsor first for approval and then once they sign off on it to the IRB. If the IRB alters, the text of the sponsor approved ad, then it must go back the sponsor and so forth until both approving bodies have nothing further to add.
Protocol Violations and Exceptions
It is the view of Dr. Woodson, our PI, that the US FDA regulations governing clinical trials recognizes that protocols are violated during the conduct of studies. It is our experience that this happens in every clinical trial for a variety of reasons and is simply unavoidable no matter how meticulous the CRC and PI.
The regulations, in his opinion have no provision for exceptions to the protocol. There is no mention in the CFR governing clinical trials about protocol deviations granted by the sponsor” or “protocol exemptions” for this or that condition. We recognize that any deviation from the protocol as written is a violation of the protocol whether the sponsor provides the site a verbal or written waver to the contrary.
The PI is responsible for the conduct of the study at the clinical trial site. The AI assesses each situation individually at the ARC. If he decides the subject is healthy and stable but with a minor not significant abnormality that is excluding her from the study, he may request a written waver from the sponsor. In doing so, he knows this is a protocol violation and he understands that the sponsor cannot give him permission written or otherwise to violate the protocol. At ARC our PI would only suggest a waver if in his opinion the condition does not represent a threat to her life and safety if she were to consent to the study and be placed on the test article. Under these circumstances, the PI may request permission to enroll the subject and it is up to the sponsor to agree to the request or deny it.
At ARC, we have made the above assessment many times and the subjects we have entered studies under those conditions have completed their trials without any incidents. We recognize enrolling a subject not in compliance with the protocol is a violation of the protocol. It is Dr. Woodson’s policy to follow the protocol and avoid asking for wavers. If the protocol is written too narrowly such that the sponsor is receiving numerous calls from investigators for exceptions, the sponsor always has the option to amend the protocol and remedy the issue.
Changing Hard or Software on Devices Measuring Outcomes During the Study
A specialty of the ARC is osteoporosis studies with change in bone density commonly being selected as a secondary outcome. If the DXA bone densitometer has to be replaced in the middle of a clinical trial special procedures are required to reduce to variability that change will have on the outcome on the subjects participating in the study at that site. The DXA coordinating centers have protocols in place to facilitate this process but they are only implemented under emergency conditions when the clinical research site has no choice but to replace the hardware or upgrade the DXA software.