How whistleblowing cost one doctor £550000

BMJ 2002; 324 doi: (Published 25 May 2002) Cite this as: BMJ 2002;324:1240

Koos Stiekema, who delayed a clinical trial by revealing his worries about it to three ethics committees, tells Tony Sheldon how he thinks whistleblowers should be protected

Dutch former medical researcher Dr Koos Stiekema is convinced of the “potentially disastrous” effects for doctors working in industry after a court's decision to award huge damages against him for whistleblowing.

Dr Stiekema left the pharmaceutical company Organon after a dispute over the design of the PENTUA (pentasaccharide in unstable angina) study into the efficacy of a new anticoagulant, pentasaccharide. He then laid his serious concerns for the lives of the trial patients before the three independent medical ethics committees that were overseeing the study.

His actions led to a claim against him for a three month delay to the study, estimated at more than Embedded Image900000 (£550000; $827000). Despite facing financial ruin, he maintains: “Doctors employed by the pharmaceutical industry are obliged to do their utmost to reduce as much as possible any risk for patients participating in clinical trials.”

If a doctor is convinced that serious concerns cannot be conveyed internally, then Dr Stiekema sees “no other way” than informing independent medical ethics committees. “Whistleblowers should first of all be the company's doctors. They have to have the faces and families of patients in mind and should really ask themselves: ‘What if the subject was my wife or child?‘”

Last December a court in Amsterdam accepted Organon's claim that Dr Stiekema had not fulfilled his obligations to confidentiality laid out in his employment contract and had, by informing the medical ethics committees of his concerns, caused “considerable financial disadvantage.”

The court ruled that his professional responsibilities did not give him a free hand to act, and it did not accept that there was no other option at that moment. Indeed it accepted that Organon had sufficient facts to be satisfied that it had fulfilled its obligations as a pharmaceutical company with regard to the professional and scientific differences concerning the PENTUA study. An appeal is now set to begin next week that will raise the issue of whether such whistleblowing can be justified on medical, moral, and legal grounds.

Professor Mike Greaves, chairman of the haemostasis and thrombosis task force of the British Society of Haematology, said in an interview with the Dutch radio station VPRO after the court's decision that Dr Stiekema's serious objections were well argued. He said that there were enormous consequences if doctors were unable to make public their ethical objections without suffering a financial burden.

Dr Stiekema, 53, who now works in Mozambique as an internist at the Maputo Central Hospital, joined Organon in 1982, rising to become a medical research manager. He was responsible for the international study into the optimal dose of pentasaccharide for preventing heart attacks or death in patients with severe unstable angina.

After serious disagreements with the company about the design of the study (see box), Dr Stiekema felt he could not take responsibility for the new design and asked to be given other work.

Organon could not find him alternative work, so he was put on paid leave while an arbitration committee was set up to consider his concerns.

However, Dr Stiekema could not agree with Organon's plans for arbitration. This involved the company appointing two arbiters and he only one. A majority would then decide the issue. He was also concerned that both Organon's arbiters had links with the company and, he felt, “could not be guaranteed to give an entirely independent view.”

Relations worsened and Organon began legal proceedings to annul his employment contract. In May 1999 a court agreed to the annulment but awarded Dr Stiekema damages of approximately Embedded Image350000. Within days of the judges' decision to annul his employment contract, he wrote to three independent medical ethics committees in France, Germany, and the United Kingdom that were overseeing the study.

Dr Stiekema argues: “All the facts, such as animal and human research data, should have been and probably were already in the medical ethics committees' possession. But they often do not have sufficient expertise to interpret all data supplied or to spot the risks, especially if the data concern entirely new chemical entities, as was the case with pentasaccharide.”

The PENTUA studies went ahead and the results were presented at a congress in the United States last year. There had been no surplus deaths, and researchers concluded that the dose had been correct.

Dr Stiekema is concerned that doctors are now under increasing pressure to accelerate clinical research, as pharmaceutical companies have “thousands of exciting new chemical entities on their shelves.”

He hopes that the debate in the Netherlands arising from his case could produce some benefits. He would like to see medical ethics committees being obliged to keep confidential information received from whistleblowers. Pharmaceutical companies in turn should be obliged to inform these external committees about all issues relating to the safety of trial patients.

Professor Andre Broekmans, Organon's director of pharmaceutical policy, said: “Stiekema had the means to raise this issue within the company but he did not exploit them to the full extent.

“Independent scientific steering committees, international experts in the field of cardiology and thrombosis, and medical ethics committees in the countries concerned accepted that Organon's position was right and ethical. In our view the scientific discussion is closed. He had an opinion but he could not get any backing for it. The study protocol was adapted to ensure patients were intensely monitored.”

What the argument was about

The dispute between Dr Stiekema and Organon was over the design of the PENTUA (pentasaccharide in unstable angina) study into the efficacy of a new anticoagulant, pentasaccharide, and the optimal dose.

Dr Stiekema proposed a “stepwise” design for the study, with two phases. In the first phase, doses of 12 mg, 8 mg, and 4 mg would be tried. In the second phase a dose lower than 4 mg would be given, provided that, at interim analysis, the 4 mg dose in the first phase had not proved ineffective. But some people in the company wanted to include a dose of 2.5 mg from the outset.

Data available at the time led Dr Stiekema to conclude that doses of less than 4 mg were unlikely to be effective. He accepts that his stepwise design would have been more cumbersome and time consuming than a one phase design.

“The core of my objection to embarking from the outset on a dose as low as 2.5 mg was that in my opinion a sponsor is obliged to do all in its power to avoid risks, certainly if these are in the magnitude of death or heart attack.

“I never said that doses lower than 4 mg could with certainty not be efficient. I even included in my original design a dose as low as 2 mg, but this was only to be embarked on if the efficacy of the drug at a higher level had indeed been shown.”

However, in November 1998 Organon concluded from its expert advice that embarking on a study using a dose of 2.5 mg was responsible.

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Whistleblower Koos Stiekema

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