Sekeres Calls for Contract Research Organization Reform

Mikkael Sekeres, MD, Vice Chair for Clinical Research at Cleveland Clinic Cancer Center and Editor-in-Chief of the American Society of Hematology (ASH) Clinical News magazine, recently wielded his editor’s pen in an editorial entitled “Contract Research Agonizations,” and a follow-up editorial with proposed solutions. His straight-from-the-gut, tough critique of contract research organizations (CROs) was borne of frustration with what he calls their “administrative kudzu,” and a desire to motivate change.

Dr. Sekeres hit a nerve. The article received a rousing response from scores of medical professionals worldwide who have endured what he characterizes as the time- and soul-sucking indignities of one too many rote process, obscure portals and laborious site delegation logs declared mandatory by the CRO “troglodytes of trial torture.”

The response of Brad S. Kahl, MD, to the article took the form of his own editorial in Clinical Advances in Hematology & Oncology, entitled “Take Back the Research”. In it, he echoes Dr. Sekeres’ concern that the administrative inflation introduced in the name of “good practice” is beginning to kill clinical research. He calls for more room for judgment, for a focus on what makes sense to assure study integrity.

Dr. Sekeres’ editorial also received a letter of support from over 80 of the leading hematologists in Europe and has reverberated to the U.S. Food and Drug Administration and its European equivalent, the European Medicines Agency. Some CROs and pharmaceutical companies even took note, and in reaction to the editorial have revised their employee training and onboarding processes.

Dr. Sekeres recognizes the imperative of carefully monitoring therapeutic clinical trials, and that CROs help ensure trial protocol compliance. He calls them the “sultans of Serious Adverse Events” but laments that role’s accompanying overkill. Some examples of frustrations he expresses about a CRO site investigation visit (SIV):

• Repeated reviews of “investigator responsibilities” for seasoned investigators
• Excessive slide presentations, sometimes accompanied by the recorded voice of the very CRO associate who sits there pushing the “advance” button
• Duplicative signatures
• A lack of understanding of the trial, the cancer being studied in the trial or basic medical terminology
• Administrative burdens that can create animosity between the site and the CRO, like email avalanches, time demands and unnecessary escalations to supervisors

Dr. Sekeres identifies high turnover, poorly trained emissaries, a perverse incentive structure and the absence of a common sense yardstick as nasty culprits in creating the “agony” of SIVs and subsequent interactions. He also argues that the rigidity and an aura of suspicion relay an institutional disrespect for the time, intelligence and integrity of investigators and study teams who are trying to explore novel therapeutics with integrity.

Dr. Sekeres attributes much of this to a lack of trust. He argues that litigation and regulation have instilled in serious professionals a fear of action and a reluctance to take personal responsibility, leading to processes that are not only dispiriting, but which he argues stymie medical progress.

To improve the tenor and effectiveness of the CRO/investigator relationship, Dr. Sekeres asserts that this assumption of trust should serve as the first rule. He suggests these specific steps:

To the study sponsor: be present at the SIV to validate its significance and provide continuity between shifting CRO associates. Keep ongoing communication lines open and collegial.

To the CRO:

• Accept the legitimacy of the investigators’ facilities, equipment and test results to avoid wasting time and losing credibility with the investigator.
• Avoid duplicative signatures. Only one investigator needs to acknowledge responsibility for trial conduct. Dr. Sekeres says, “There are days we wish we were famous athletes, or rock stars, or even reality TV stars, and that our signatures were collectible and fetched a high price. But the hard fact — and we have to face this daily when we stare in the mirror and see ourselves for the hematologists we are — is that our signatures are worthless.”
• Stop placing the burden of navigating complex electronic data systems on study personnel.
• Avoid playing politics.
• Set reasonable deadlines and recognize that emailing study personnel multiple times weekly will actually delay a study from opening or data from being collected.

At the close of Dr. Sekeres’ second editorial, he summarizes his plea to the CROs of this world in this way:

“All of our suggestions boil down to issues of trust and mutual respect. If you trust and respect us, we will provide you the information you need. And we will actually respect you a lot more.”