I loved your column , Dr . Sekeres . Being involved in clinical research and new drug development since the 1990s , I could have written it word-for-word . The real “ cancer ” is bureaucracy , and it is an expensive one .
Each session of monitoring for any new compound is longer than the previous ones . The real target of all this is not patient safety ; it is self-protection of the CROs and the pharmaceutical companies . Who will stop the madness ?
Please send your editorial to the U . S . Food and Drug Administration , the European Medicines Agency , the executives of professional organizations , and patient / parent associations .
— André Baruchel , MD , PhD Pediatric Hematology-
Immunology Department University Hospital
Robert Debré ( APHP ) Paris , France
Mikkael ’ s article about working with CROs is spot on . I only wish clinical trial sponsors would someday realize how much time and energy is being spent on completing unproductive forms and fulfilling requirements at the expense of the really important information , including disease and protocol knowledge and sensible data capture .
The best sponsors are the ones who don ’ t use CROs . Somebody should write an article on queries – another area where common sense is lacking . Timelines for Institutional Review Board approval and activation would be halved if we had no CRO assisting with study startup .
— Janet Briel , RN , MBA Johns Hopkins School of Medicine
Baltimore , MD
I really enjoyed this article . At last someone has a knack for voicing the frustrations in a quite humorous way . Hope the CROs read this article and stop badgering the MDs and principal investigators who have worked on numerous trials .
— Ramachandran Subramanyam Roswell Park Cancer Institute
Buffalo , NY
A Return to Common Sense in Clinical Research
The responses came from far and wide : Steven Le Gouill , MD , PhD , from the Department of Hematology at Nantes University Hospital and the Centre Hospitalier Universitaire in France , wrote that he “ hoped [ the ] article will be a first step in bringing back some bon sens in clinical research .” Below , Dr . Le Gouill , Simon Rule , MD ( Plymouth University , United Kingdom ), and more than 80 European colleagues present a call for a return to common sense in clinical research . ( Visit ashclinicalnews . org / perspectives / CROs to read the full list of signatories .)
The editorial by Mikkael Sekeres , MD , MS , in the June issue of ASH Clinical News perfectly describes a site initiation visit ( SIV ) conducted by what Dr . Sekeres termed a “ contract research agonization ” ( CRA ) and the madness that modern clinical research has become . The constant reference to “ quality ” has paradoxically became synonymous with mindless , needless , and ultimately counterproductive bureaucracy . It is time to start questioning the necessity of some aspects of the clinical trials data-collection process , particularly those that cause daily hassles before , during , and after a clinical trial – sometimes years after publication .
Like our American colleagues , European investigators are plagued by the CRA parasite . At this stage , it is worth repeating the definition of a parasite : a living being feeding itself at the expense of the organism that shelters it . The SIV described by Dr . Sekeres is sadly identical to the SIV in Europe , with the addition of some local complications . For instance , we must date all documents according to U . S . format ( MM / DD / YYYY ) rather than European format ( DD / MM / YYYY ). If this is not followed , the documents have to be changed and multiple queries ensue .
European investigators also complain of the countless emails that flood their inboxes documenting serious adverse events ( SAEs ) and suspected unexpected serious adverse reactions ( SUSARs ). This is all done in the name of safety , but here is where the paradox lies . The deluge of SAE reports identifies toxicities ( such as neutropenic sepsis on the chemotherapy control arm , or infusion-related toxicity with a 20-yearold antibody therapy , or progressive disease in tumors unrelated to the trial in question ). Add to that the SUSAR reports that are evidently not serious , nor even expected , and toxicity-reporting becomes less safe because no one can see the wood for the trees .
No one in the industry takes responsibility for looking for true toxicities of concern , so researchers are sent everything . The CRA industry has created its own rules requiring electronic sign-off to acknowledge receipt of these reports . No one has the time to read these , and , if one does , there is rarely ( if ever ) any toxicity information that is valuable to the clinician running the trial . Trials are now less safe as a consequence .
There are also the never-ending passwords to constantly renew and the famous questionnaire of feasibility emailed to you that invariably begins with the same question : “ What is your email address ?”
We are reaching a point where the paperwork and what we are being asked to do is descending into absurdity . Are increased administrative procedures the price we must pay for a guarantee of the quality of scientific projects ? Are we all condemned to say nothing , do nothing , and suffer ? The answer to all these questions must be “ non , no , nein , and niet !” We , the doctors and researchers who treat patients , are the true clinical research specialists . It is therefore our duty to stop the administrative inflation introduced in the name of “ good practice ” that is beginning to kill clinical research , demotivate clinical research teams , scare away young clinicians , and unnecessarily disperse the limited financial resources that should go toward improving care and science . How could we not denounce a business model that does nothing for patients , unreasonably increases the cost of clinical trials , and ultimately benefits only the industry that invented it ?
Worse , these harassments inhibit all creativity and initiative . Imagine what would have happened if CRAs had preceded the discovery of fire some 400,000 years ago . Humanity would have remained in the dark , living in caves , eating raw meat , and hoping not to be eaten . And why ? Because humanity would not have been able to prospectively investigate the interest of fire according to the so-called good practices , as established by CRAs . If humanity had been able to prospectively investigate the role of fire according to modern research criteria , the conclusion of the phase I trial would have been that fire is too toxic because of too many AEs and SAEs , such as grade 3 “ meat overcooking ,” grade 4 “ burns ,” and grade 5 “ cave fire .”
Today , the question of interest is no longer whether clinical research should continue on its path of administrative absurdity , but how to stop this madness without harming the quality of scientific data . The pharmaceutical industry needs to engage properly with the regulators and stop interpreting what they believe is expected of them . Those of us who still run academic studies within the same regulatory frameworks know full well that most of what is being asked for in the name of quality and safety is not required .
The CRAs have created a lucrative industry for themselves and needlessly generate work that only serves to perpetuate their existence with no tangible benefit to the patient . In the medical world , we are mandated to produce evidence before we can change practice ; we would like to see any evidence that clinical research is safer today than it was 10 years ago .
We believe that the time has come for academic societies ( such as the American Society of Hematology , the American Society of Clinical Oncology , the European Society for Medical Oncology , and the European Hematology Association ) and cooperative groups involved in clinical research to challenge this pernicious culture and produce recommendations for good practice . This needs to be done in concert with the regulators , but the interpretation of safety and quality should not rest with those at arm ’ s length from the patient or the drug company , and whose business depends on generating paperwork to justify spiralling costs .
It is our duty as both clinicians and citizens to reverse this trend and bring common sense back to research . Ultimately , it is the patient who will miss out on innovation if this continues . ●
Have a comment about an article ? Let us know what you think ; we welcome your feedback . Email the editor at ACNEditor @ hematology . org .
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