Fraud and Misconduct

Fraud is often coupled with misconduct and the two are certainly related; fraud by definition is misconduct, but not all misconduct is fraud. Fraud always contains intent whilst misconduct covers a wide range of activities, from carelessness, right through to deliberate deception.

The word misconduct is used differently in English. Therefore, there are different definitions. According to the UK Medical Research Council and the Wellcome Foundation, misconduct is defined as:

Alternatively, the Joint Consensus Conference, Edinburgh, (1999) defined it as:

In contrast, a definition of clinical research fraud is clearer:

Sponsors of clinical trials and doctors participating in clinical trials (investigators) put a lot of emphasis on planning, performing and evaluating clinical trials. This is to ensure that the trial results in:

• Trustworthy data.
• Clear results and treatment recommendations.
  

The data are generated by the investigators who enrol the participants into the trial they perform the measurements and observations. Findings are documented in Case Report Forms (CRFs) prepared by the sponsor. The Good Clinical Practice (GCP) standard defines the conditions that sponsors and investigators have to apply to ensure good quality data. Auditing the trial performance at the investigator’s site ensures that the trial is carried out properly. However, some investigators may decide to falsify or even invent data.

This topic explains the following:

• The difference between ‘misconduct’ and ‘fraud’ – examples are provided.
• Ways to prevent, detect and handle fraud and misconduct. 

The conduct of most clinical research is honest and adheres to ethical principles. Occasionally the sponsor or organiser of a clinical research project may be faced with data which are questionable, such data may or may not be fraudulent.

Fraud should not occur at all. However, we do not live in an ideal world… Crimes do happen everywhere. The following three examples of fraud from different regions in the world demonstrate what happens when fraud is committed.

Between 2004 and 2005, Professor Woo-Suk Hwang, a highly regarded, highly funded South Korean researcher at Seoul National University, achieved international fame for his work on embryonic stem cells and the promises his findings offered. Considered a national hero, he had surprised the world with his report of creating 11 patient specific stem cell lines. His reputation was quickly destroyed, however, and his research activities were halted when his success in somatic cell nuclear transfer (SCNT – a method of ‘cloning’) became mired in scandal, particularly when it emerged that many of his data on SCNT were made up. He lost his university position and his two important papers on embryonic stem cell research had to be retracted from the journal ‘Science’.

Read more about the case here: Wikipedia and here.

 

Several ethics violations were committed by his team members during the course of their research. In 2009, Hwang was convicted of misusing research funds and illegally buying human eggs for his research. Among many transgressions was the dubious manner in which the team persuaded women to donate their eggs for their SCNT research. Investigations revealed that many of the women who provided eggs had not given valid, informed consent, and nearly 75% of them reported that they were given cash or offered various financial incentives.

Some of the women who provided eggs were infertile patients who had agreed to donate any excess eggs following their fertility treatment. What they weren’t told, however, was that their eggs were initially assigned a quality grade, and the higher marked eggs were set aside for research while the lower graded ones were used for their treatment. Others who agreed to donate for the cause of research alone were not fully informed of the potential risks and harms involved in the egg donation process or the nature of the research for which their eggs would be used.

Concerns about probable coercion later surfaced when it became clear that at least two of the egg donors were junior members of Hwang’s research team. One, a PhD student, was listed as a co¬author of the 2004 Science paper. The other, apparently reluctant, was escorted to the donor clinic by Hwang himself. Given the precarious position in which they presumably found themselves, the reported pressure to donate seems obvious.

The other chief concern raised by the method of gaining eggs was the payment that many of the women received. Some eggs were purchased directly, while in other cases women received compensation in the form of discounted fertility treatment. Though the concerns of egg trafficking – i.e. that women will be unduly pressured to donate despite the inherent risks are well agreed upon, there is no international consensus on the acceptability of selling eggs. There were no legal restrictions in place at the time of Hwang’s actions.

The large number of eggs Hwang used in his SCNT experiments was staggering. The Ministry of Health and Welfare reported that Hwang acquired 2,221 eggs from 119 women while the Prosecutors’ Office reported that 2,236 eggs were acquired from 122 women. Additionally, there were eggs that were retrieved from excised ovaries. The total number of eggs purchased or traded was 1,649, approximately 75% of the total number of eggs the Hwang lab used for research.

Tackling research misconduct

• Prevention.
  
• Detection.
  
• Investigation.
  
• Prosecution.
  

For research involving clinical trials, standards were set in the ICH Good Clinical Practice (GCP) guidelines.

In Europe, these standards are set in the EC Directives on Clinical Trials (2001/20/EC)* and on Good Clinical Practice (GCP) (2005/28/EC), which encompass ICH¬GCP. These are now enacted throughout Europe. All Clinical trials guidelines, guidance documents and underlying legislation can be found in Volume 10 of the publication "The rules governing medicinal products in the European Union". Link to the publication: EudraLex - Volume 10 (europa.eu)

Misconduct and fraud destroy the trust of the public in clinical research and harms the patients treated on the basis of invented or unreliable study results. Therefore, misconduct and fraud must be prevented if ever possible. If it happens, it needs to be detected, carefully investigated and rigorously prosecuted where appropriate.

Unintentional misconduct can be best prevented by training people and explaining to them why it is so important that they adhere to the quality standards for the conduct of clinical trials.

The prevention of misconduct must come first. But, if misconduct or fraud occurs despite the setting of these standards and training in their operation, then corrective procedures must be in place.

When misconduct is detected:

In clinical trials misconduct and fraud are often identified by monitors checking the case report forms (CRFs) and trial performance at the sites. These people are called ‘Clinical Research Associates’ (CRAs). But also the ‘Auditors’ sent to the sites by the sponsors to check the overall study performance and the GCP Inspectors sent by the competent authorities detect these problems. Sometimes suspicious data only become obvious once the statistician checks the overall set of data and detects special ‘patterns’, less variability or lack of outliers.

An important source of fraud and misconduct detection are collaborators and team members. This might be a very difficult situation for them as they may have to blame a colleague, friend or boss of having done something wrong. It is important that these ‘whistle blowers’ receive the required attention and protection.

In an ideal situation, misbehaviour or errors are detected by the researcher himself. People should be encouraged to announce their mistakes. They will only do so if they work in an environment where people are not punished for their mistakes. Instead the reason(s) for the misconduct should be detected and the team should work together to prevent this from happening again.