1 Nimmo WS, ed. Joint consensus conference on misconduct in biomedical research. Proc R Coll Physicians Edinb 2000;30(Suppl. 7).
2 Kevles DJ. The Baltimore case:a trial of politics, science, and character. New'York: Norton, 1987.
3 Medawar P. Advice to a young scientist. Cambridge: Harper and Row, 1979.
4 Broad W,Wade N. Betrayers of the truth. New York: Simon and Schuster, 1982.
5 Kohn A. False prophets. Oxford: Blackwell, 1986.
6 Association of American Medical Colleges. The maintenance of high ethical standards in the conduct of research. Washington DC: AAMC, 1982.
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5: Counteracting research misconduct: a decade of British pharmaceutical industry action
This book deals in depth with the subject of fraud and misconduct in the context of biomedical research as a whole.This specific chapter deals with the role and experience of the pharmaceutical industry in the UK, now over a period of over 10 years, in preventing, detecting, investigating, and prosecuting such fraud and misconduct. It stands as a stark contrast to the inactivity seen outside the industry and outside the UK.
The welfare of patients is fundamental to the practice of medicine.That there are so many effective treatments available for the cure or control of so many diseases is largely the outcome of decades of research, stretching throughout the second half of the 20th century. Much research must continue, both to improve upon existing treatments and to master diseases including the cancers, psychoses, dementia, and many others, which are currently untreatable successfully. Clinical research therefore remains essential, including genetic and biotechnological research, with the recognition that the interests of patient-subjects involved in such research must be safeguarded. The Declaration of Helsinki sets out the principles of such safeguards, and its regular revision by the World Medical Association emphasises its paramount importance.1
Fraud in clinical research can be defined as "the generation of false data with the intent to deceive". This definition includes all of the components of fraud: the making-up of information that does not exist, and intending to do so flagrantly in order to deceive others into believing that the information is true. Exploitation in the context of clinical research is one of the greatest potential hazards to the welfare of individual patients and, indeed, to society as a whole. Such exploitation is rare, though quantifying its actual likelihood remains difficult. There is enough published evidence to confirm that fraud in clinical research is ever-present.2
Fraud in any context is deplorable, but if it is primarily prescription, tax, or financial fraud then the only party at risk is the one who loses money - and this may be the Government or, ultimately, the taxpayer. Research fraud distorts the database on which many decisions may be made, possibly adversely affecting thousands of others. Clinical research fraud is potentially even more dangerous: if licensing decisions regarding medicines were to be made based on efficacy and safety data that are false, the result could be disastrous. Furthermore, individual patients may be the unwitting victims, believing that the unexpectedly frequent and intensive care that they are receiving - including numerous blood tests, ECGs and other investigations - demonstrate dedication on the part of the doctor, whereas they are being flagrantly exploited without them realising it. The importance of the roles of both the clinical trial monitor and the independent auditor in this regard cannot be overemphasised. Nevertheless they are inadequate by themselves: when a fraudster is determined to cheat and to cover his tracks, auditors are hoodwinked into believing that all is well.
Ideally, fraud should not occur - but we do not live in an ideal world; agreed high standards must be set for clinical research, to which all interested parties should adhere. However, procedures must also be in place if misconduct is suspected despite the existence of these standards. Within the pharmaceutical industry, the standards needed for the conduct of clinical research already exist, and have been adopted by all the regulatory bodies who license medicines, international pharmaceutical companies and contract research organisations. Both the European Commission (CPMP) Good Clinical Practice (GCP) guidelines3 and the requirements of the FDA came first, but GCP guidelines, adopted under the International Conference on Harmonisation (ICH) process,4 now take precedence, globally. The Step 5 stage having been reached, there is now global guidance - which means that there are now global standards - that have been adopted by the three major sectors of Europe, the USA, and Japan. A European Commission directive on clinical research will soon be operative throughout Europe, once individual member states have adopted it, thus giving the force of law to the ICH GCP agreement. Although the standards referred to above are therefore in place, there is no such harmonisation when it comes to dealing with fraud and misconduct in the context of clinical research. Indeed, even within Europe there is as yet no agreed attitude towards tackling the problem.
Fraud is much less common than carelessness, although, as indicated above, its incidence is difficult to quantify. Lock has referred to the various estimates that been made5 but, based on the work on cases of fraud in which I have been involved during the last 10 years, my personal belief is that it is at least 1%. If we accept this figure of 1%, this means that, in the UK where I am based, maybe 30 studies are being conducted at any one time that could be fraudulent. Extrapolating this to the rest of the world - and there is no evidence that the incidence of fraud in clinical research differs across Europe or North America (although we are more open in dealing with it in the UK) - then there may be between 125 and 150 clinical trials being conducted, now, where some of the data being generated are fraudulent, where investigators are making up some of the data to be submitted to a company and - worst of all - may be exploiting their patients in the process. But, whatever its incidence, this unacceptable aspect of clinical research must be tackled if we are to achieve and maintain confidence in scientific integrity and in the clinical research process.
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