Clinical Trial Sponsors, Investigators and Institutional Review Boards Must Bare the Responsibility of Subject Safety

Events leading to the most recent high profile subject death in a gene therapy clinical trial are yet another indication of the lack of understanding, poor application of regulatory standards and in some cases lack of effective regulatory oversight in the United States (US).

Having been involved with clinical research for well over 13 years, I have encountered on numerous occasions, clinical trial sponsors and investigators that lack a basic understanding of US and/or international regulatory requirements or are unable to apply regulatory requirements effectively. This ultimately leads to poor clinical trial design and execution. What is of primary concern is that many of the sponsors, investigators and Institutional Review Boards (SIIs) involved with clinical research, apply only the basic content of the regulatory requirements to their clinical research, which represents the bare minimum level of compliance and is a dangerous and unacceptable practice.

The US Food and Drug Administration (FDA) and other international regulatory agencies state that regulations are not all encompassing and merely define the minimum level of required compliance for the conduct of clinical research.  It is the expectation of regulatory agencies that SIIs  apply best practices and industry standards above and beyond the minimum regulatory requirements.  Such best practices and industry standards must be described and defined by SIIs and applied to the unique characteristics of each of their clinical research studies and investigational products. It is ultimately the responsibility of SIIs to build upon the basic requirements defined by regulatory agencies.  Any organization involved with clinical research whose mantra reads “…if it is not in the regulations then we don’t have to do it…” will eventually cause serious injury or death to a clinical trial subject or at the very least, compromise the integrity of the clinical trial data generated.

If US and international regulatory requirements and guidances seem vague, this is for a reason. These regulations must apply to a diverse spectrum of biologics, drugs and medical devices, and therefore must generally define the basic rules for the conduct of clinical research. Again, the ultimate responsibility for the effective conduct of clinical trials rests upon those entities that apply the regulations and subject humans to investigational products. 

There are, however,  notable issues with US FDA’s regulatory oversight. Being a seasoned Good Clinical Practice (GCP) auditor, I routinely identify significant levels of noncompliance at clinical study sites. Such substantive issues identified by GCP auditors many times are not discovered during US FDA inspections of sponsors and/or investigational sites. Discussions of this topic at industry conferences and within peer groups indicate that this trend is more common than not, and speaks volumes to the effectiveness of US FDA’s overburdened and under funded efforts to ensure FDA’s protection of the rights and welfare of human research subjects.  Having said this, one should not be so quick to point the finger at US FDA’s regulatory oversight, when taking into consideration the lack of acceptable funding and support that the current US government provides the agency: An agency established to ensure the safety of the US population as it relates to foods, drugs and cosmetics.

The crux of the issues related to clinical trial subject safety can ultimately be traced back to those sponsors, investigators and IRBs that purport regulatory understanding and compliance and that, in a great many instances, let their corporate and professional egos stand in the way of the application of effective practices that would ensure a higher level of subject safety that should already be inherent in the field of clinical research.

Tobin C. Guarnacci,

President

CliniQAl, Inc.