Clinical research is fundamental to the advancement of medical practice and improving the outcomes for our patients. This is without question, but evidence based medicine requires the generation of evidence and it is the process behind this that has evolved to a place where it may become self-defeating.

Year after year, clinical research teams and investigating physicians are subjected to an exponential growth in the administrative burden, paperwork, and regulation associated with clinical trials. The fault for this increase in bureaucracy is caused at all levels. The law has not appreciably changed since 2001, but those administering it or working within it are producing increasing bureaucratic demands. The universal explanation for this ever-increasing workload is that it represents “good clinical practice” (GCP) and is there to support the safety of the patient and the integrity of the research. It is impossible to disagree with those aims, however this deluge of bureaucracy is in danger of having the opposite effect. We are inundated with multiple amendments, many of which are of no clinical relevance, receive information on side effects that have been known about for many years, or SUSARs (Suspected Unexpected Serious Adverse Reactions) that are neither serious or unexpected, as well as countless clinically insignificant queries. All of these have to be acknowledged through online, password protected systems which are different for different trials and can mean having to do this multiple times if you are running multiple studies with the same drug.

Many of these trials are run by Contract Research Organisations (CRO’s) who work as intermediaries between the drug companies and the researchers and have created an industry that has developed many of these processes.  More often than not the representatives of these companies have little knowledge about the pathology or clinical features of the disease in question, which in itself leads to endless unnecessary questions and further paperwork when they come to sites to monitor patients within trials. These processes take up an inordinate amount of time and in some way help explain the exponential rising cost of clinical trials and in part the rising price of new drugs.

One unintended side effect of both uncontrolled bureaucracy and the increasing cost of clinical trials will be the rapid disappearance of independent academic clinical research or the ability of new investigators to be able to engage in clinical research.

This opinion piece has been signed by almost 1000 senior researchers in haematology from across Europe. Most have been involved with clinical research for years and are fortunate in having research teams around them that help with this ever-increasing workload, but for new investigators without any infrastructure to support them clinical research has become too time consuming and challenging to engage with.

But where are the regulators in this process? Unfortunately, they have set the tone through their own inspection processes that are used as a validation by the drug companies and CRO’s for the bureaucratic systems that we now have. The justification is always that this is about patient safety. However, many of us believe research is less safe today as the deluge of unimportant information that follows the opening of a trial means that the truly important signals are lost and the length and language used in consent forms mean that patients no longer truly understand what they are getting involved with. Where is the “good clinical practice” in asking a patient to re-consent to a trial (often multiple times) to acknowledge new side effects in a drug that they never received, or to re-consent to having fewer investigations and this continues even after they are no longer on the study. Consent forms are dozens of pages long, often confuse patients, and on occasions can scare them. The impact of this goes un-recognised, but any challenge to this process is regarded as tantamount to serious professional misconduct. This is setting a tone that many investigators are no longer willing to tolerate.

The declaration of Helsinki and ICH-GCP are there to provide a framework to ensure the quality integrity and safety of all research. These principles are fundamental and beyond question. They  have not changed, however the processes used to ensure compliance to these principles have been allowed to run out of control and are in danger of defeating their purpose. We believe it is time for our health authorities to urgently review the whole system in order to truly ensure patient safety and medical progress. This review should involve the pharmaceutical companies, independent research organisations, charitable organisations that fund research, clinical teams running studies and most importantly actual patients.  We feel a new framework is required that changes the way research is administered to rebalance the system away from an industry that has created most of it back to a focus on the patient and those with the primary responsibility of looking after them.

 

Simon Rule, Professor of haematology, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK

Competing interests: None declared

 

 

Steven LeGouill, Professor of haematology, University of Nantes, Nantes, France

Competing interests: None declared