Helsetilsynet

In a letter of 4 July 2006, the Norwegian Board of Health in Oslo and Akershus requested the Norwegian Board of Health (the central office) to apply for prosecution on the grounds of fabrication and manipulation of research, indicated in the report from the investigative commission appointed by the Rikshospitalet-Radiumhospitalet Medical Center and the University of Oslo. The report was submitted on 30 June 2006.
 
In a letter of 5 July 2006, the Norwegian Board of Health submitted a formal complaint and request for an investigation into a possible criminal offence to the Oslo Police District. The information contained in the report is of a nature that, in the assessment of the Norwegian Board of Health, it indicates a violation of Sections 4 and 16 of the Health Personnel Act, which come under the scope of the penalty provisions in Section 67 of the same Act and Section 48 a of the Penal Code.
 
At the request of the Norwegian Board of Health, the documents that are available in the case that was filed against you by the Norwegian Board of Health in Oslo and Akershus were forwarded to us in a letter of 10 July 2006.
 
In a letter of 15 August 2006, you were notified that the Norwegian Board of Health would review your licence to practice as physician and dentist, and you were requested to provide a statement regarding the case. We received a statement from you and your lawyer Lyngtveit in a letter of 6 September 2006. We have also received a statement from the Rikshospitalet-Radiumhospitalet Medical Center by Stein Vaaler in a letter of 14 September 2006. You provided your comments to his statement in your letter of 5 October 2006.
 
A meeting was held at the offices of the Norwegian Board of Health on 10 October  2006, on which occasion you and your lawyer Lyngtveit were given the opportunity to elaborate on your statement in the case. We received your comments on the minutes of the meeting in your letter of 23 October 2006.

The case as it appears from the case documents

The reason for initiating a supervision case against you was that matters that were clearly inconsistent with the actual circumstances were discovered in the article of which you were the primary author in the October 2005 issue of the internationally respected journal The Lancet. On 12 January  2006 you admitted that you had fabricated some of the data on which the article was based.
 
You appear to have explained to the Investigation Commission that the relevant data are based on a series of data published under the auspices of the Cancer Registry of Norway, the Norwegian Institute of Public Health, and other institutions. The data include data on smoking habits, alcohol consumption and cancer rates. You compiled a list of cancer rates according to age group and periods of time, and then inserted tentative birth dates for fictitious patients. The list was supplemented with fictitious NSAID use, different classes/types, various dosages, various time intervals, to illustrate how various conditions were distributed between the patients and the control group with different risks of developing oral cancer from smoking habits. You have explained that this was originally meant purely as a simulated database. The article presented it as though it consisted of actual patients.
 
On the basis of data from the simulated database, you write in the Lancet article that the cox-2 receptors in the mouth are stimulated in areas of the oral mucosa that are dysplastic. Since NSAIDs inhibit cox-2 activity, the use of NSAIDs can have a beneficial effect on potential cancer development. You write that mortality rates did not decline in spite of this and that the reason for this is the cardiovascular side-effects of NSAIDs. Instead of dying of cancer, some patients risked dying of heart attacks and strokes. Dr. Ernest Hawk of the National Cancer Institute in the USA had already reported this result at a hearing in February 2005. The health authorities in the USA issued a warning against the cardiovascular side-effects of non-selective NSAIDs on 7 April 2005.
 
Rikshospitalet-Radiumhospitalet Medical Center and the University of Oslo appointed an investigation committee with detailed terms of reference on the basis of your admission that you had fabricated the data on which the Lancet article was based. All your scientific work from 1993 to 2006 was investigated. The investigation report states (the following text is translated by Rikshospitalet-Radiumhospitalet Medical Center, and the full report is available in English translation …):

Jon Sudbø began his PhD project in 1993 under the supervision of Albrecht Reith.

The PhD project consists of two separate parts. One part involves theoretical and applied works on tissue architecture in cancerous tumors and normal tissue. The Commission has not found indications of research flaws related to these works.

As reflected in his subsequent research, most of his PhD project involved characterizing the early stages of oral cancer. The research question was whether and, if so, to what extent, different types of classifications of white patches in the oral cavity were indicative of a high risk for developing oral cancer. The doctoral dissertation and related publications give an affirmative response to this question, asserting that a classification based on DNA content can with great accuracy predict the subsequent development of cancer.

First published in the highly respected New England Journal of Medicine in 2001, this sensational finding was based on DNA analyses of 150 patients with leukoplakia (i.e. 'white patches' that may be early stages of oral cancer) in the oral cavity. In 2004, a second article was published in the New England Journal of Medicine, based on further investigations of the same 150 patients. Based on their own investigations and those made by the Cancer Registry of Norway, the Commission's point of departure is that there are serious problems associated with this crucial patient material. For instance, the same patient appears several times. As far as the Commission can determine, the material consists of 141 different patients at the most, since several patients are represented by several tissue samples that collectively add up to 150. Further, the Commission has found that 69 of the 141 patients included in the study should have been excluded because they had been diagnosed with oral cancer before or at the same time as the leukoplakia was diagnosed. For these patients, it was not possible to study the future development of cancer, since they already had cancer. This error alone is so serious that the results and the conclusions are invalid. The Commission has also uncovered several other inconsistencies. For example, the age distribution in the data files is not consistent with the underlying patient material. Further, the Commission has noted that the reported 150 DNA analyses are to some extent repetitions of data from a far smaller number of patients. The reporting on how DNA analyses and the classification of leukoplakia were conducted (by several observers) is also incorrect and misleading.

Consequently, the Commission has determined that the data underlying parts of the PhD project, as well as several other publications, are not sufficiently consistent with the actual facts the Commission has found it reasonable to take into account. The internal affairs investigation conducted by the Cancer Registry of Norway has arrived at the same conclusion.

The Commission is of the opinion that the errors and defects that have been exposed are too numerous, too great and too obvious to be attributed to random errors, incompetence or the like; and that the raw data therefore appear to have been fabricated, manipulated and adapted to the desired findings.
 
To sum up, the investigation report shows that conducting a thorough and verifiable review of the facts of this case has been a very complicated process. However, the Investigation Commission were able to establish with a high degree of certainty that, among the patients identified in your data file, there are at least 69 individuals who should have been excluded because they had oral cancer prior to, or simultaneously with, the dysplasia in question. This conclusion is supported by independent information from several sources.
 
Your statement of 6 September 2006 states: “I admit that the underlying data for the October 2005 Lancet article were based on assumptions and were not the actual data as stated in the article. Similarly, I admitted to the Investigation Commission that our article in the New England Journal of Medicine (NEJM) of 2004 did not necessarily represent complete mortality data as was the impression one might get from reading the article. I regret these matters in the strongest terms.”
 
As regards the data on which your PhD is based, you have stated that you repeatedly asked the Investigation Commission for access to the data lists from the Cancer Registry’s linking in 1996 and 2006, but did not get it. These links would, among other findings, have uncovered inconsistencies in how many patients had cancer before and after the dysplasia was diagnosed. Otherwise, you have no comments regarding this inconsistency.
 
You further state that you are of the opinion that there were 226 patients who where not linked in the Norwegian Cancer Register in 1996, and that the Commission was probably not aware of a large number of tissue blocks stored at the Clinic for Pathology at the Rikshospitalet-Radiumhospitalet Medical Center. You cannot guarantee that the Commission has been given access to all the relevant documents in this case. You maintain that it is speculative to ascribe the inability to reconstruct the total number of analyzed patients to dishonesty.
 
You believe that Tables 2 and 3 in the report are incorrectly presented by the commission. The section at the bottom of page 79 in the report, in which the commission concluded that the lists to which it had access – and which were the basis for your PhD – is incomprehensible to you. You also point to other errors in the report.
 
According to the statement from the Rikshospitalet-Radiumhospitalet Medical Center of 14 September 2006, a ploidity analysis was introduced as a prognostic method to separate leukoplakia with a high potential for malignancy from the others based on your published research results. The Pathology Clinic has established ploidity analysis based on your publication from 2001. As we understand it you were not involved in this routine diagnosis.

The assessment of the Norwegian Board of Health

The Norwegian Board of Health's assessment is that the above-mentioned circumstances are of such a nature that they constitute grounds for revoking your authorization as a physician and dentist in accordance with Section 57, paragraph one of the Norwegian Health Personnel Act, which states that:
 
"The Norwegian Board of Health may revoke an authorisation, licence or certificate of completion of specialist training if the holder is unfit to practice his profession in a responsible manner for reasons of severe mental illness, mental or physical impairment, prolonged absence from the profession, use of alcohol or narcotics or substances with a similar effect, a gross lack of professional insight, irresponsible conduct, gross breach of duty pursuant to this Act or provisions stipulated in accordance with this Act, or due to behaviour considered to be incompatible with professional conduct.”
 
The topic of our assessment is whether you are unsuitable to practice your profession as a physician and dentist because of conduct considered incompatible with such professional practice. In that regard, we refer to the fact that one of the objectives of the authorization scheme is to contribute to instilling trust in health care personnel and the health services. The professions of physician and dentist are professions that require a high degree of general trust. Stringent requirements are placed on the ethical attitudes and conduct of the individual physician and dentist.
 
It is indicated in Proposition to the Odelsting, No. 13 (1998-1999) that there is a need, on a more general basis, for a condition for withdrawal of authorization that can justify the revocation of authorization. In earlier acts relating to physicians and dentists, this condition was formulated as “conduct unbecoming a physician/dentist”. In the Health Personnel Act the condition was changed to “conduct considered incompatible with the practice of his or her profession", in order to relate the condition more closely to the practice of the profession. As a rule, the supervision authorities should not intervene in the case of behaviour which is worthy of criticism, but which has nothing to do with practice of the profession, unless the behaviour is related to very serious matters.
 
According to Section 3 (8) of the Specialized Health Services Act, research is one of the tasks that hospitals must especially carry out. Thus, medical research is a part of the health services and may be part of the practice of the profession as both physician and dentist. Research may, among other things, form the basis for the development of new treatment methods for the benefit of patients. It is therefore critical that research results that are published are founded on data that are correct.
 
The Norwegian Board of Health generally notes that all medical research can have significance in terms of diagnosing and treating patients. This connection is obvious in cases where research is performed on patient samples. The aim of research will  often be to improve diagnosis and treatment. Verifiability and accuracy are absolutely necessary and completely fundamental to all research. To a significant extent, all modern medicine is based on research. The health services and the general public must be able to trust the research results published in internationally renowned journals. According to the assessment of the Norwegian Board of Health, strict requirements must therefore be placed on the conduct of health care personnel in connection with research.
 
The Norwegian Board of Health bases its conclusions on the admitted circumstances. You have admitted that the Lancet article is founded on erroneous data. You used a simulated database, but presented it as actual patient data, and described findings that indicate that the use of NSAIDs may be beneficial in relation to the potential development of cancer. Furthermore, it was indicated that mortality would not decline because NSAIDs would have cardiovascular side-effects. In the assessment of the Norwegian Board of Health, to describe such findings on the basis of false data is an act that is extremely serious and gives evidence of your lack of judgment about the possible consequences for future patients. The Norwegian Board of Health is of the opinion that you have behaved dishonestly in connection with this article. By adhering to improper research practices you have lost trust. Improper research practices will furthermore weaken trust in practice of your profession in general. We find that your actions were a wilful breach of proper research practices, and that you acted in a manner that was scientifically dishonest.
 
The Norwegian Board of Health notes that basing research published in a scientific article in an internationally respected journal on fabricated data is such a severe breach of what is expected of the conduct of a physician/dentist that the Norwegian Board of Health finds that general trust in you as a physician and a dentist has been seriously impaired. This is the case even though it cannot be documented that patients have suffered as a consequence of the Lancet article. In the assessment of the Norwegian Board of Health, such conduct is incompatible with the practice of your profession both as a physician and a dentist.
 
As regards the Investigation Commission’s conclusion regarding your PhD, in which it was maintained that the underlying data seem to have been manipulated and fabricated, you contested that in your statement to the Norwegian Board of Health. However, you did not present more detailed documentation that could confirm your objections. The Norwegian Board of Health has not found it necessary to perform a concrete evaluation of the evidence regarding the matters stated in the investigation report, since the improper research practices in connection with the Lancet article are sufficient to conclude that you have exhibited conduct incompatible with the practice of your profession. However, we note that the matters subject to criticism indicated in the investigative report would further weaken trust in the practice of your profession.

On the basis of what is stated above, the Norwegian Board of Health hereby revokes your authorization as physician and dentist in accordance with Section 57 of the Health Personnel Act.

Pursuant to Section 68 of the Health Personnel Act, this decision may be appealed to the Norwegian Appeals Board for Health Personnel. The time limit for lodging a complaint is three – 3 – weeks from receipt of this letter, in accordance with the enclosed notification. Any complaint must be sent to the Norwegian Board of Health, which will then forward it to the Appeals Board. The application of this decision may only be brought before a court of law after any appeal to the Appeals Board has been exercised, in accordance with Section 71 of the Norwegian Health Personnel Act.
 
Yours sincerely,

Lars E. Hanssen

Sylvi Storaas
Senior Adviser

Cc:
Lawyer, Erling O. Lyngtveit
Norwegian Board of Health in Oslo and Akershus
Rikshospitalet-Radiumhospitalet Medical Center

Executive Officer: Sylvi Storaas
Executive Officer – Health Care Specialist: Senior Adviser, Grethe H. Hoddevik