tipology:editorial

numero rivista e pagine: HSR Proceedings in Intensive Care and Cardiovascular Anesthesia 2010; 2(2): 77-79
PDF version

Ethics and methodology, not bureaucracy

Authors: G. Landoni*, A. Zangrillo

Department of Anesthesia and Intensive Care, UniversitÓ Vita-Salute San Raffaele, Milan, Italy

Corresponding author: * Corresponding author:
Giovanni Landoni, M.D.
Department of Cardiothoracic Anaesthesia and Intensive Care,
UniversitÓ Vita-Salute San Raffaele
Via Olgettina, 60 - 20132 Milan, Italy
E-mail: landoni.giovanni@hsr.it

We have a dream that within ten years, patients admitted to teaching hospitals will long to be enrolled in “researcher driven”*randomized clinical trials. Patients will be fully aware of the reduced complication rates and the improved outcomes that occur in patients involved in randomized clinical trials, the so-called “Hawthorne effect”.
We have a dreamthat within ten years scientists will not have to spend months waiting for ethics committee approval and will not have to raise thousands of Euros in funds to carry out their research. On the contrary, they will have a 50% salary increase as they are spending their creative and enthusiastic energies to perform clinical trials (at present, hospitals receive several thousand Euros from the Ministry of Health for each published article, yet the clinical scientist generally knows nothing about it).
Although both “company driven” and “researcher driven” research are important and useful, the differences are striking. Unfortunately, patients, medical doctors and legislators do not seem to be fully aware of these differences. One reason for this might be the influence of international insurance, pharmaceutical and quality-control lobbies.
Today, a clinical scientist who wants to compare two forms of treatment that have routinely been used in clinical practice for around 20 years, two slightly different dosages of the same drug, or use a safe drug at a lower dosage with slightly different indications is obliged to:
1) prepare hundreds of pages of documentation (most of the time not in English, but in a language not generally used by the scientific community);
2) wait from six to twelve months for ethics committee approval (which at times never arrives);
3) pay a Contract Research Organization (CRO) for the quality monitoring of the study;
4) pay a CRO for the pharmacovigilance of the study (even if the drug has been used in clinical practice for 20 years on millions of patients);
5) pay specific insurance for all patients enrolled in the study

Considering that it can take from one to two years to receive a grant (from its ideation to its funding) and that protocol approval takes a year, we are generally forced to observe our ideas while they agonize under the weight of bureaucracy and fundraising requirements.
We have a dream that within ten years the same clinical scientist will have his idea approved by an ethics commission made up of peers and patients after only a few weeks and will randomize hundreds of patients in just a few days using established multicenter networks without costs or bureaucracy. In Italy, for example, we have more than 100 cardiac surgery centers that perform around 40,000 cardiac surgery operations every year. It would be simple and cheap to compare inotropic or vasoconstrictor agents in perioperative cardiac failure; to identify if the widespread use of diuretics in the management of acute renal failure is useful, useless, or dangerous, to compare anesthesia techniques and drugs, or investigate preventive measures or curative drugs for the prevention or treatment of cardiological, nephrological, or neurological complications. We would need networking, a simple national web-based database and regular meetings (either online or in person).
In intensive care the situation is almost grotesque. Most patients are unconscious and therefore cannot provide written informed consent, which means they cannot benefit from inclusion in researcher driven randomized clinical trials according to the interpretation of many ethics committees. As a result, critically ill patients have no evidence-based medicine guidelines to support the life-saving treatment they are receiving.
Hospitals that carry out clinical research perform better than those that do not. Patients (and Patients’ Associations) should ask to become involved in “researcher driven” trials. They should go to those hospitals where “researcher driven” trials are performed and ask to be enrolled in ongoing trials. In fact, patients enrolled in “researcher driven” clinical trials have improved outcomes, irrespective of the assigned treatment or control. This so-called “Hawthorne effect” can be explained, in part, by the superior knowledge and skill of the medical doctors/departments where research is performed and by the additional attention that all the medical and nursing staff dedicates to these patients. “Research driven” trials should involve every patient that is admitted to a high-standard hospital. There is so much to discover and each patient should be studied and benefit from inclusion in randomized protocols.
Two factors limit this extraordinary opportunity: bureaucracy and ignorance. International and European laws in this field are excellent where “company driven” trials are concerned, but limit “researcher driven” trials and thus, indirectly, kill thousands of patients every year. 
Of course, clinical research has to be studied at Universities and Master Courses and clinical scientists need to possess strong methodology and should receive incentives to disclose any conflict of interest. What we all need is Ethics and Methodology, not Bureaucracy. Our dream is to reach this objective within 10 years. We believe we can do it and we are certain that all of our patients will benefit greatly from it.

*For this editorial the following definitions will be used: "company driven" trials include phase I,II (III) trials on new drugs with safety issues and economical implications; "researcher driven" trials include phase (III) IV trials on "old" drugs ("generics") or techniques used in various combinations, or for new indications with no safety issues or economical implications. The clinical has no conflict of interest with the drug company. Patient management is carried out using the best available treatment, the only difference being randomization to treatment or control; "in between" trials include phase (II) III (IV) trials that resemble "the researcher driven" type, but are actually "company driven"