In September 1994 a major international pharmaceutical company commenced a randomised multinational multicentre comparative Phase IV clinical trial on the effects of a new formulation of an established medicine on high risk patients with hypertension. The company arranged that the UK component of this trial should be supervised by a contract research organisation. The study divided patients into two treatment groups in a randomised double blind fashion involving treatment for a total of three years.12
One of the investigators chosen was a GP whose surgery was located in a rural village. He had previously conducted research for the contract research organisation and other companies, and was considered an experienced investigator. He signed the protocol, the investigators' agreement and the financial agreement. Monitoring visits were subsequently conducted by clinical research associates from the contract research organisation, but they experienced considerable difficulty in arranging the necessary visits with the doctor.When eventually a visit took place certain discrepancies were noted. These included the presence of trial medication for several patients, which was purported to have been dispensed, entries included in the clinical report forms for dates when the doctor was allegedly on holiday, and the absence of any correlation between the NHS notes for three patients and their purported clinical trial record forms.
A further monitoring visit three weeks later confirmed that medication reported in the record forms for certain patients as having been supplied had not been dispensed, as the drugs were still present, unopened, at the surgery premises. The irregularities noted on these two monitoring visits were reported to the sponsoring company. After some difficulty in arranging a confirmed date, in part attributable to the doctor's purported vacation in Italy, when he was in fact at home, an audit visit was made. A subsequent audit visit was made one month later and both audits revealed more discrepancies. Over and above the irregularities noted by the clinical trial monitor, it now appeared that certain original NHS notes had been removed and replaced with study specific information only.
The company concluded that a number of issues had not been satisfactorily explained, and that it was not possible to know to what extent the patients identified by the doctor in this clinical trial had participated. The case was then referred to the ABPI for comment, and thence to MedicoLegal Investigations. Certain further investigations were therefore conducted, and the services of a handwriting analyst were engaged. The evidence from the handwriting analyst, Mr MG Hall, concluded that the signatures of 17 patients on the consent forms and of 17 witnesses, also on the consent forms, were similar to the handwriting of the doctor. Five patients were interviewed, and they confirmed that they had not been asked to take part in this study, that the signatures on the consent forms were not theirs, and therefore forgeries, and some of the witnesses' signatures were also forgeries.
The case was referred to the General Medical Council, but was never heard because the doctor died before any hearing could take place. The circumstances of his death may be relevant to his involvement in not only this study but also a large number of other studies where irregularities were subsequently discovered, including the falsification of trial results and the forging of patient signatures in over 150 patient consent forms.The doctor was aware that this incriminating evidence, which had been hidden away, had been found and that these several further cases were also under forensic investigation. However, all these investigations came to an abrupt halt when the doctor was found dead in the bottom of his swimming pool. The post-mortem report indicated that the doctor had drowned and the coroner returned an open verdict.
The other doctor who died was a partner in a general practice in the Cotswolds. The question of fraud as far as he was concerned first came to light when he admitted to one of his partners that he was suicidal, and that one of the reasons why was that he had fabricated some of the data for a number of clinical trials in which he was involved as an investigator. Professional help was provided for the doctor, but despite this, and being rested from work, some weeks later he committed suicide.
Several features came to light after his death. Firstly, the triggering factor to his admitting to fraud to his partners was probably that he had been found out by at least one of the companies sponsoring a study. This occurred when the chairman of the local research ethics committee discovered that the doctor had sent to this company an approval letter, purporting to come from the committee, which was forged. No submission for this trial had ever been received, let alone considered, by the committee and clearly no letter of approval could possibly have been issued.
The magnitude of his fraudulent activities did not become apparent to anyone until after his death. His former partners needed to ensure that any patients who had been involved in his research activities, whether fraudulent or not, were adequately safeguarded. This proved to be exceedingly difficult, as the doctor had seemingly generated medical records solely for the purposes of source document verification, which he showed to the various clinical trial monitors, but had not indicated anything about clinical trial involvement in the main practice records, which were computerised. Virtually none of the patients, who were ostensibly subjects in these various clinical trials, were aware of their so-called involvement, but neither did most of them receive any study medication. The consent forms were either forged or signed at the doctor's behest for other purposes. Most of the trial supplies were disposed of down the toilet, but the doctor went to sufficient trouble to make it appear that drug reconciliation was reasonable. He arranged for visits from clinical trial monitors always to be held after surgery hours when no patients would be present, nor any other members of the practice partnership or staff. Apparently he kept his partners aware of his interest in research by doing the occasional study authentically, but kept them in the dark about most of his study activities, including those he had fabricated, and consequently kept for himself the payments he subsequently received.
Several observations arise from this case. As an aside, it can be noted that the forging of research ethics committee approval is not unique, as the experience of Blunt referred to elsewhere in this book (Chapter 13) confirms. The pharmaceutical companies concerned were identified only after a considerable amount of detective work, and were dismayed that they themselves had not detected anything suspicious that required further investigation. However, the doctor had clearly gone to considerable lengths to conceal what he was doing, and in my experience fraudsters such as he are classic confidence tricksters, appearing to their patients, their partners and colleagues, and the sponsors of research to be totally beyond reproach. Because all the correspondence between the doctor and the sponsoring companies or contract research organisations had used his home address, and because the trial agreements had been solely between the doctor and the sponsoring company, his partners were quite unaware of the extent of his involvement in clinical trials. If they had been, they might have had a controlling influence, although they might have been surprised that the local research ethics committee was seemingly allowing him to do so much research at the same time - unaware that he was bypassing such approval by forging it.
It should therefore be an accepted policy, enshrined in company standard operating procedures, that agreements involving general practitioner investigators should include a signed statement from or on behalf of any other partners that the practice as a whole is satisfied with the arrangements made for the conduct of that particular study at that particular site. Correspondence should ideally be addressed to the investigator at the practice premises, and monitoring visits should always be made on the actual site where the patient-subjects are being seen. The same principles apply to hospital-based studies, where it should go without saying that an agreement must be signed by the relevant authorities as well as by the investigator.
Was this article helpful?
Do You Suffer From High Blood Pressure? Do You Feel Like This Silent Killer Might Be Stalking You? Have you been diagnosed or pre-hypertension and hypertension? Then JOIN THE CROWD Nearly 1 in 3 adults in the United States suffer from High Blood Pressure and only 1 in 3 adults are actually aware that they have it.