MedicoLegal Investigations Ltd.

Eight years of battling by MLI

Dealing with the biggest conman we have ever met has been a massive struggle, not just for MLI, but for everyone concerned with the attempt to get justice in this case. What started as suspicion of dishonesty by Sharma within the former company Sanofi Synthelabo led to MLI involvement in 2000. There were no doubts, something serious was happening but it was impossible to identify causes because issues within so-called ‘Investigator Initiated’ studies were not accessible. The investigator owned the data and no one other than him had information about the patients in these dubious studies.

MLI was instructed by Sanofi Synthelabo when Dr Cathy Baxter, then Medical Adviser and Dr Sue Griffith, Medical Director, expressed deep concern to the Board of the company. It was agreed that we should seek cooperation from the Institute of Psychiatry (IOP), a ‘centre of excellence’ at Kings College, London. We wrote a straightforward introductory letter to Professor Robin Murray seeking a meeting. The letter was very carefully worded and emphasis was given to the fact that Dr Sharma must be regarded as innocent of any impropriety until proven otherwise. A meeting took place a few days later when four other members of the Institute were present. Once again we stressed that Dr Sharma must be regarded as innocent, as in our letter, and we explained the nature of our investigation. Professor Murray asked, “Off the record, what is the worst case scenario for the Institute?” Dr Wells told him that in all our investigations we go back over a number of years if we find evidence of serious misconduct. He went on to explain that in almost all of our cases additional wrong-doing had been unearthed but at no time did either of us accuse Dr Sharma of any wrong-doing because, at that stage, we had no clear evidence. After the meeting which was rather unproductive, we wrote expressing thanks for seeing us. Yet again, we included in the letter that Dr Sharma must be regarded as innocent of any impropriety until proven otherwise. It was as if a sixth sense was telling me there was trouble ahead.

I then received a telephone call from Kings from someone telling me he had been asked to conduct an internal investigation at the IOP. He sought information from me as to what he should be seeking. I told him I was unable to assist him because I was not in a position to share information with him for fear of contaminating any evidence later.

An extraordinary letter to MLI from Dr Lynn Carlisle, Institute Secretary, and dated 19th April 2001 referred to our 'unsolicited approach' and ‘serious allegations’ against Sharma. She wrote that an internal investigation had been completed and that Sharma had been completely exonerated from any wrong-doing. She continued by stating, “You should be aware that the outcome of our investigation and Dr Sharma’s exoneration has been circulated widely both within and beyond the Institute especially to the pharmaceutical companies that Dr Sharma has been associated with”.

The next bombshell to hit MLI was a letter from Peter Carter-Ruck, solicitors, indicating defamation proceedings against us in the High Court. We then became aware that the Institute had produced notes of our initial meeting and given them to Dr Sharma. These notes, if believed, would have constituted defamation as we were recorded as having said that Sharma had been dishonest for many years. ‘Inaccurate’ is probably the most generous way to describe those notes which, significantly, were signed and dated two weeks after the meeting.

Fortunately MLI had professional indemnity insurance for such an event and our insurers provided for us the finest legal brains at Wiggin & Co, Cheltenham. They instructed Adrienne Page QC and Matthew Nicklin of Counsel. It was a formidable team, but expensive. As time passed we realised that there was a possibility that the million pound cover we had might run out. If that happened, we were warned, we could lose our homes.

The High Court case against us was a major ‘own goal’ by Sharma who had to produce documents and explanations to support his case. This gave us missing pieces to the massive jigsaw puzzle we were trying to assemble. When the case collapsed and MLI’s integrity was restored to the full, doors began to open and evidence sufficient to trigger General Medical Council proceedings eventually came our way. Sharma’s case was destroyed; Peter Carter-Ruck withdrew their support to Sharma on their no-win-no-fee basis. He was left to face GMC proceedings. At that time he was represented by solicitors acting for his medical defence body. However, for reasons unknown to us they too ceased to act for him long before his case was called.

Having submitted our case to the General Medical Council we were in the hands of Field, Fisher Waterhouse (FFW), solicitors in the City of London. It was whilst working with them for six years in the 1990’s (following a CID career in the Metropolitan Police) that I learnt about the GMC process, the Medical Act and the peculiarities of the health sector. There was a time when we could have worked alongside them in putting together the final stages of the case. This is eminently sensible because we know the shortcuts and pitfalls, but in this case we were considered ‘persona non grata’ and there was no communication between us at their request. They were fearful of being accused of having us influence their process and therefore damaging the case. Now there are excellent lawyers at FFW and I cannot fault their integrity or ability. However they are not detectives and therefore cannot be expected to investigate professionally any more than a GP can expect to offer brain surgery at his local practice! A lawyer will ask a pharmaceutical company to send all documentation relevant to a case and then in his/her office plough through thousands of documents most of which are irrelevant. A detective will go to a pharmaceutical company, carry out an interview and ask for documents that are referred to in that interview. He will then return to his office with what he needs. Documents that are used will be served on the defence at the appropriate time as well as a further list of unused documents – the ones that we took possession of but were not, in our later view, relevant. This is the disclosure process and the lawyers create for themselves huge piles of unused material to be served on the defence. This is costly and very time consuming.

Our case was being finalised by FFW for almost five years before reaching a hearing. I consider that to be totally unacceptable. I believe that when a case is as serious as this one there should be a fast-track system. The Panel eventually adjudicating in this case deemed it so serious that they not only struck off Sharma but ordered his immediate suspension from the Medical Register during the appeal period. They used the strongest sanction available to them – for the protection of patients. But he had been working for eight years after he was first identified as troublesome; at what risk to patients we cannot know.

More worrying still is that if there was no MLI no one would have taken this case on board. We asked the GMC to take it on in 2001 because of the enormity of it and the difficulties encountered at that stage. I think it was probably a failure to understand by an administrator that led to their declining to take it on board. I had had the same experience in 1997 when I went to them with the basics of a case in the Professor Southall saga. I also asked them to delegate their powers to MLI to demand information under the year 2000 extension to the Medical Act but this was also refused. It is not a police matter; the UK licensing authority, the MHRA, will not investigate suspicion and no lawyer in the country would have unearthed what we found. It so happens that with past experience we have learned to understand malpractice in research and for some extraordinary reason there’s no one else in Europe doing what MLI does.

I am very proud of the MLI team that stood firm in this case despite the most enormous pressure to crack. Bullying will never stop us and if we believe there are patients being exploited (it is usually the vulnerable ones) we will leave no stone unturned to identify serious misconduct or fraud. Some of the US and UK pharmaceutical companies regarded Sharma as a most valuable ‘world opinion leader’ and for them, his credibility far exceeded ours even though we have a proven track record. Lack of support thankfully did not apply to Sanofi Synthelabo or Novartis. Both companies made it absolutely clear that patient safety is a priority and their support for MLI was unlimited. It was truly refreshing but it would have been so easy for them to step aside once we had been (wrongly) accused of defamation.

Peter Jay

The Investigation

‘Daunting’ was the first thought I had when I saw the boxes and piles of paper that made up the evidence against Dr Tonmoy Sharma. My first task on joining MLI Ltd in the Spring of 2002 was to use this vast amount of paper to prepare the case for submission to the General Medical Council (GMC).

Peter and Jonathan Jay had taken statements from many people; Medical Advisers and Directors in several pharmaceutical companies, Monitors and Auditors, Sharma’s co-workers and co-investigators, and other experts in the disease areas covered by Sharma’s research. There were papers from Sharma’s employers, from an American university, and from Chairmen of Ethics Committees (EC). The sheer volume of paper was incredible, and my job was to review it all and write a report bringing all areas together into a logical and coherent document that would lead the assessors at the GMC to an understanding of the amazing and tortuous deceits that he had committed. Many events had taken place concurrently, so even getting the papers into a logical order was far from straightforward.

But the only way to achieve what we wanted was to tackle the papers one by one, taking copious notes for myself, and making sure that all the papers were clearly marked and identified so that I could come back to them easily later. Slowly, with much cross-reference from file to file, a story emerged. That story was a shocking one, detailing one man’s abuse of the drug research process and his exploitation of vulnerable patients, spread over many years. He claimed to be an expert in clinical research, yet wrote to one company that he did not need Ethics Committee approval for a particular study because it was very similar to one he’d done the year before, and as that study did have EC approval, he could just transfer it across. His arrogance was apparent in every document I read, and every sheet of paper shouted to me of abuse of patients, most of whom in Sharma’s studies had acute schizophrenia and so were in a poor position to stand up for their own rights.

Gradually the summary needed for submission to the GMC came together. It ran to 13 pages, a number that was clearly going to be unlucky for somebody. There were several areas covered; the lack of relevant EC approval in more than one study, exploitation of employees and other research staff, a set of case record forms given to Sharma by one company for their study but photocopied and used by him in a study paid for by another company, several incidences of financial impropriety, and even an episode where a medical charity was misled.

So the submission was made to the GMC, and the long wait began.

Dr Jane Barrett

Industry View

This decision by the GMC represents the culmination of many years of collaborative effort by individuals, companies, the ABPI and not least MLI to bring the details of this complex case together and have it finally heard in the appropriate forum. Despite many obstructions along the way it is testament to the diligence of MLI that this case has now been heard and has finally reached a successful conclusion.

Dr Cathy Baxter, former Medical Adviser, Sanofi

In-House Training

If you are unable to subscribe, why not have our team visit your company for a full day’s training on Research Fraud Awareness and Interview Technique. By having it in-house, entire QA departments and teams of CRAs can receive up-to-date training on all aspects of research fraud awareness.

Annual Subscription And In-House Training Courses

Don’t lose vital time and data through clinical trial fraud or misconduct: Make MLI part of your GCP procedures

Research fraud and misconduct can seriously affect the outcome of your clinical development programme. Identifying possible research fraud and then knowing how to investigate it are challenges for all pharmaceutical physicians and their colleagues who are involved in clinical research.
MLI has long sought to train the pharmaceutical industry and the NHS in the identification and investigation of research fraud and misconduct. Our organisation can only exist with the ongoing support of industry - the next time your clinical development programme is in jeopardy because an investigator is not performing appropriately you will want to turn to MLI for advice and assistance. We can only offer that help and assistance if we have your support.

There are two ways in which your company can support MLI.

Annual Subscriptions In-House Training Courses

Annual Subscription

For a small annual subscription payment, companies can have peace of mind knowing that when misconduct surfaces, MLI will be available for that necessary support and advice. GCP procedures are tightening especially now with the EU Directive in place. Companies that subscribe will receive benefits such as reduced rates for investigations, free attendance at for-cause audits and cost reduction for training courses.

In-House Training Courses

Now is a good time to ensure that your staff are ahead of European inspectors. All clinical research personnel should be regularly updated and trained in critical aspects of good clinical practice. MLI will organise tailored in-house courses for your teams during your annual GCP training. Delegates will also be taught investigative skills to help with interviews particularly at for-cause audits.

Approximate timings

09:15 Registration

09:30 - 10:15 Background to Research Fraud/Taking Action EEC Directive Considerations — Dr Jane Barrett

The history of fraud in clinical research, the impact of company SOPs and EC directive are all
discussed.

10:30 - 11:30 The Investigation Process/Case Studies/Learning from the past - Peter Jay

This session provides an insight into the means of detecting fraud and the process of prosecution in UK and abroad. Patient’s reactions to exploitation and the consequences of failing to react to suspicion.

11:30 - 12:45 Introduction to Interview Technique - Jonathan Jay

An interview technique which has been developed for CRAs and Auditors to use at monitoring visits and audits. An interactive session designed to highlight individual weaknesses and to boost confidence.

13:30 - 17:00 Clinical Research Fraud Exercise & Suspect Interview Technique Training —Jonathan Jay

This session is role play orientated. Delegates are placed in teams and are given a fraud exercise to investigate. Trial documentation is available to find hidden fraud/misconduct. Examples are taken from previous cases. Delegates are taught an investigative interview technique to help them in preparation for an interview of Dr Mendacious at the end of the training day. Teams are de-briefed at the end and are given the opportunity to ask questions.

MLI needs your support in making the United Kingdom the safest place in the world to conduct clinical research

Statutory Requirement to Report all Serious Breaches to MHRA

In August 2006, Regulation 29A of the Medicines for Human Use (Clinical Trials) Regulations 2004 was amended by Statutory Instrument 2006/1928 to require the notification of serious breaches of GCP or trial protocol. On 23rd February 2007 the MHRA published guidance on this amendment (www.mhra.gov.uk).

One of the purposes of the guidance was to provide advice on what should and what should not be classified as a serious breach and therefore what must be reported. The responsibility for notifying the MHRA lies with the sponsor but where a sponsor has delegated responsibility to a CRO then the latter should comply. Notification should occur within 7 days of the sponsor becoming aware of the breach and that is when the clock starts not necessarily when the breach occurred.

Investigation of the breach may occur in parallel with the 7 day period or after it but it is that time limit that is paramount. Occasionally, investigation will be required prior to informing the MHRA to ascertain whether the breach is serious. Once that decision has been reached then the clock starts. A template form for reporting breaches is attached to the guidance along with some worked examples.

What is likely to be considered serious? Where the safety or physical or mental integrity of the subject(s) of the trial or the scientific value of the trial is significantly affected.

Not all cases of confirmed clinical trial misconduct have to be reported but the MHRA encourages it on a voluntary basis. If the breach has occurred outside the UK but the trial has UK sites then this should be reported to MHRA.

The MHRA may take a number of actions when receiving such reports. They include acknowledgement and no immediate action, if appropriate action has already been taken by the sponsor, a request for more information or investigation by the sponsor or referral to a professional body e.g. the GMC.

Where does MLI fit into this new process? The sponsor might wish an independent organisation to investigate the issue either on their own behalf or having been invited to further investigate by the MHRA. MLI is also expert at preparing evidence for professional bodies particularly the GMC—remember of 27 completed cases referred to the GMC by MLI, 26 were found guilty of serious professional misconduct.

Key learning: Sponsors now have a statutory duty to report all serious breaches of GCP to the MHRA

Dr Richard Tiner