In 1990 and early 1991 a pharmaceutical company undertook a multicentre Phase II/III clinical trial, intended as a pivotal registration study, for the treatment of perennial allergic rhinoconjunctivitis.The trial was conducted to standards of Good Clinical Research Practice, and included an assessment of haematology and biochemistry; patients were required to complete diary cards.10
The company recruited a number of general practitioners to conduct this study including a Dr P Daengsvang of Liverpool. Dr Daengsvang had previously participated in another study carried out by the company, and his conduct of this previous study had been satisfactory. He was approached again by the company and asked if he would be interested in taking part in this new study, and, having studied the protocol, he signed an agreement to follow the procedures outlined in the protocol. He also signed a financial agreement and was visited by the clinical trial monitor and given supplies of documents and trial medication for him to recruit 15 patients.
Dr Daengsvang recruited patients so quickly that he requested, and was granted, facilities to recruit an additional 10 patients. Within 10 weeks he had recruited a total of 20 patients, and was eventually visited again by the clinical trial monitor to collect the completed case record forms and residual trial material. The company review of the returned record forms raised suspicion because of the uncommon cleanliness of the patient diaries and the "perfection" of the study data. A comparison was made with the progress and results in the other centres taking part in the study.
From a site audit conducted at Dr Daengsvang's surgery and the comparative review, conclusions were reached as noted in Table 5.1.
Table 5.1 Conclusions from site audit and comparative review.
1. Number of patients enrolled, and eligibility
No. enrolled No. eligible after run-in Other centres 148 112
Dr Daengsvang 20 20
It is highly unlikely that this difference is due to chance (P = 0.008)
2. Patients completing one month's treatment
No. eligible No. completed
Other centres 112 83
Dr Daengsvang 20 20
It is highly unlikely that this difference is due to chance (P = 0.007)
3. Change in haemoglobin from entry to the end of the study
Change of < 2g/dl Change of > 2g/dl Other centres 83 1
Dr Daengsvang 14 6
It is highly unlikely that this difference is due to chance (P < 0.001)
The company next submitted photocopies of the consent forms allegedly signed by the 20 patients recruited by Dr Daengsvang, and 19 original patient diaries to the Division of Questioned Documents of the Laboratory of the Government Chemist. The conclusions were:
• The patient entries on a number of diaries were probably written by one person.
• The entries were unlikely to have been written on a daily basis.
• The authentic writing of Dr Daengsvang shows similarities with the patient entries in 16 of the diaries.
The audit at Dr Daengsvang's surgery yielded the following relevant details:
• The NHS records of at least four patients indicated that they had been seen by the doctor on the alleged study dates but for reasons not related to the study.
• For one study patient the NHS record date of birth had been altered from 1914 to 1974. However, the recorded medical history and living circumstances corresponded to a patient aged 76, not a patient aged 16.
The case was considered at length, and it was concluded that Dr Daengsvang violated the protocol for this trial:
• by using real patients as phantom subjects in the trial, possibly requiring some of them to have unnecessary blood tests;
• by using post-treatment blood samples taken from different subjects than at entry to the study;
• by tampering with NHS records so as to provide spurious source document verification;
• by completing some of the patient diaries himself; and
• by generating false data on certain case report forms, and in so doing demonstrated serious professional misconduct, justifying referral to the General Medical Council.
At a hearing before the Professional Conduct Committee, heard in his absence, Dr Daengsvang was found guilty of serious professional misconduct, and his name was erased from the Medical Register.
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