Hospital Pharmacist
Vol 9 No 8 p214
September 2002

Fraud and misconduct in research

By Stephen I. Ankier, PhD, FRPharmS

Although the Medicines Act 1968 regulates (inter alia) authority to start a clinical trial, there is no current UK legislation to control the complex processes whereby a trial is designed, conducted, monitored, audited, recorded, analysed and reported. This will change when principles of a new European Union directive on good clinical practice (GCP) in clinical trials are incorporated into UK law by 1 May 2004. Although the directive is mainly concerned with GCP, several of its Articles now under consultation will also impact on directives for good manufacturing practice for medicinal products.

The principles of GCP have for many years remained the scientific and ethical "gold standard" for organising clinical trials in the UK. Nevertheless, there have been a few cases of clinical research fraud or misconduct by investigators, each of which had the potential to pervert the database of acquired knowledge whether or not misdemeanours were due to deliberate fraudulent deception, innocent mistakes or ignorance. Hospital pharmacists often work in a pivotal position to witness and report such events. For example, they may interact with the study sponsor and may also be delegated responsibilities by the investigator or his institution for maintaining records of the delivery, use by each research subject and return to the sponsor of investigative medicinal products (IMPs).

When the EU directive is incorporated into UK law, it is expected that there will be some changes¹ of importance to research sponsors and/or manufacturers of clinical trial materials and these changes may also be significant to many hospital pharmacists. Such changes are likely to include:

• Authorisation by the Medicines Control Agency (MCA) for the manufacture, or importation of IMPs from outside the EU or European Economic Area

• A qualified person with responsibility for the manufacture, release and control of all batches of IMPs in accordance with existing and several expected revisions to current EU guidance on defined standards of GMP

• New mandatory labelling requirements for IMPS

• The appointment of inspectors to assess compliance with GMP, GCP and good laboratory practice at sites involved with clinical trials

• A 60-day time limit for ethics committees (ECs) to make decisions about proposals to perform clinical trials

• The need for MCA authorisation and EC approval for non-therapeutic Phase I clinical pharmacology studies in healthy volunteers

It is a concern that the results of a recent survey² showed that nearly 70 per cent of respondents working in the NHS, hospitals or academia, did not have standard operating procedures (SOPs) to deal with research fraud or misconduct. Therefore, to become compliant with current and developing requirements, it is essential for organisations involved in clinical research to establish and update a comprehensive set of written SOPs for both GMP and GCP which also include policies, guidelines and procedures to manage transgressions. This matter requires urgent attention since the Department of Health's research governance includes the requirement for systems to be put in place to detect and address fraud and other scientific or professional misconduct by their staff.³

Where effective SOPs to deal with research fraud or misconduct are still not available or where existing SOPs remain inadequate, misapplied or are abused, the Public Interest Disclosure Act 1998 (PIDA) protects employees (called whistleblowers) from victimisation should they raise genuine concerns about a category of malpractice specified in the Act. The initial disclosure, whether or not it is correct or confidential, should normally be made to a manager, a director or the employer within the whistleblower's own workplace to resolve any problems within that organisation. For a hospital pharmacist, disclosure may be directly to the sponsoring department. To qualify as a "protected disclosure" under the Act, the disclosure of any alleged malpractice must be made in good faith. Victimisation (ie, suffering a "detriment" or "dismissal") is recognised under the PIDA which also provides legal recourse for the genuine whistleblower who is victimised.

Procedures should ensure that, in the early stages of an internal investigation of an alleged misdemeanour, the main concerns are to verify the facts, to alleviate the whistleblower's fear of being victimised while also ensuring that the accused party is not automatically stigmatised as a miscreant.⁴ Examples of research malpractice involving a breach of GMP or GCP, which could come to the attention of an hospital pharmacist, might be tampering with trial medication, sealed randomisation labels or envelopes or discovering that subjects were being included in a clinical trial without their consent or for which regulatory approval or EC approval had not been obtained.

The lack of a detailed knowledge of GMP and GCP militates against a witness of a malpractice from voicing concerns as also might an individuals' conflicting self-interests and the lack of a whistleblower's personal assertiveness. Such factors can not be regulated for by law. Hence, it is important to change the ethos of organisations where research is performed so that the genuine whistleblower is regarded as a concerned witness of a possible malpractice who wishes to promote the integrity of research as well as their own organisation's accountability and continued good reputation.

Guidance about how pharmacists should deal with the specific issue of research malpractice is awaited from the Royal Pharmaceutical Society as are details of expected new legal provisions. However, when the directive is fully incorporated into UK law, the continuing professional status of hospital pharmacists will depend on them becoming adept practitioners of both GCP and applicable Articles impacting on GMP. Moreover, there is a continuing need for comprehensive working SOPs to manage research projects which also specify applicable procedures whenever malpractice is suspected, detected or proven. The PIDA remains available as current legislation for use whenever managerial and organisational systems have failed.