Report from the Investigation Commission appointed by Rikshospitalet – Radiumhospitalet mc and the University of Oslo January 18, 2006

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5.3 In particular about the NCI application and Lancet article

During the period 2000-2001 Jon Sudbø and Albrecht Reith as mentioned got the idea for a new and larger study. Also this study was related to the prevention of oral cancer, but this time it was to be a prospective study in which they were to follow patients forward in time. The study was named PROTOCOL, which stands for Prospective randomized trial on preventing oral carcinomas from oral leukoplakia.

In 2000/2001 Jon Sudbø prepared a protocol. Following internal discussions at the Radiumhospitalet it was suggested that the protocol should be translated into English, as the potential was considered to be big, and that it ought to be an international study. Jon Sudbø translated the protocol himself in the summer 2001.

At the same time Sudbø and Reith applied for support to the project from Health and Rehabilitation via the Cancer Society. They were granted funds for the years 2002 until December 31, 2005.

In 2002-2003, Jon Sudbø and Albrecht Reith were fairly often in the USA for seminars and the like. In that connection they came into contact with Scott Lippmann and the professional community relating to MD Anderson, as well as Andrew Dannenberg of Weill Medical College at Cornell University. This contact gradually developed into a professional collaboration. This collaboration resulted in agreement to apply to National Cancer Institute (NCI) for funds for a large study. Sudbø’s PROTOCOL study was to be included as an element in this study. The application was submitted to NCI in the summer of 2003.

Jon Sudbø has stated that at the same time, that is in the beginning of 2003, he started working on the data list which later on was to form the basis for the article in The Lancet, which has a certain connection to the NCI study by a preliminary version of these data being included in the application according to Lippmann, but without having a central role. Jon Sudbø has stated to the Commission that the basis for this data list is a series of data published under the auspices of the Cancer Registry and the Norwegian Institute of Public Health, among other institutions. These are data relating to tobacco habits, cancer and other relevant factors.

Thus, he made a table of cancer incidents in various age groups and various periods of time, and then entered tentative dates of birth for fictitious patients. In other words, the list is based on qualified guesswork. The list was supplemented by fictitious use of NSAID, various types, various doses, various time intervals, such that one could see how various factors were distributed on patients and the control group, with different risk of getting oral cancer based on smoking habits. Sudbø has stated that this originally was meant as a pure simulation data base – i.e. fictitious number experiments. Nothing has come to light to indicate that other persons knew about this.

The further time and sequence of events are somewhat unclear to the Commission. However, the Commission has had access to the comprehensive correspondence that took place between Jon Sudbø and the bio statistician at the MD Anderson, J. Jack Lee. This correspondence documents in detail how Jon Sudbø managed to produce the fabricated data file which forms the basis for the Lancet article. The communication between Sudbø and Lee per email with data files attached, shows how Jon Sudbø first sent a fictitious data file to J. Jack Lee.

The Commission will not discuss this in detail, but would emphasize that the common theme in the correspondence is that J. Jack Lee points out errors, defects and inconsistent factors in the file he had received. Then Jon Sudbø accounts for how he will have these regrettable errors corrected, errors which according to Sudbø must be based on misunderstandings and other unfortunate circumstances. According to Sudbø’s accounts per email to Lee, the correction of errors was made in cooperation with qualified specialists and institutions. An email of January 29, 2005 states, for example:

“I checked also with the health survey people, who scrambled on Saturday. The confirmed alcohol was not a selection criterion for the original search.”
Jon Sudbø writes in an e-mail of March 29, 2005 to Jack Lee:

”Albrecht and I will be in meetings with CONOR (Cohort of Norway), the consortium which administers

the databases of the health surveys. We need to make sure we have documented all there is to document

regarding these surveys and how they are linked to other population based disease registries.”

Another example of Sudbø demonstrating his will to work day and night with this project and his access to not only competent specialists but also to the registers in Norway is in an email dated June 6, 2005, in which he writes to Scott Lippman, J. Jack Lee and Andrew Dannenberg:
“Please find attached clean copies of the NSAID paper, cover letter and responses. Jon Mork and I spent

most of the weekend at the Cancer registry, checking the number of cases with cancers in different

locations of the oral cavity. We have also had a meeting to go over the final drafts

of the paper, responses and cover letter.”

An e-mail of September 30, 2005 states:

“Tonight, I have gone through and discussed the commentators viewpoints and the responses from Jack,

with epidemiologists at the Cancer Registry. They ([N.N.], lead epidemiologist on Jon Morks 2001 NEJM

paper, and [N.N.] also epidemiologist at the Cancer Registry and on the Mork 2001 paper) found the

responses to the point, and well placed. In other circumstances, this should get us on dry land with respect

to acceptance.”

It must be noted that the Commission is of the opinion that it is not likely that these meetings took place, or that Sudbø or any of the mentioned persons had such access to the Cancer Registry and such information.

The application to NCI was granted in March 2004, and the total grant was for approximately NOK 70 million. However, the project is mainly an American project directed by Scott Lippmann and MD Anderson. Jon Sudbø’s PROTOCOL project only got a small part of this grant. According to Sudbø, at least NOK 16.5 million was to be transferred to the Radiumhospitalet in the course of a five years’ period. He refers to the Norwegian project being one of four projects included in the total application (a so-called Program Project Grant).

In the summer and autumn of 2004, an application was made to the Regional Committee for Medical Research Ethics South Norway (REC-South) and the Data Inspectorate for approval of the PROTOCOL study. The study was approved on August 13, 2005 and October 19, 2004, respectively.

The PROTOCOL study was opened for inclusion of patients in December 2005. When it became known through media that the Lancet article probably was based on fabricated research data, this study was stopped for an indefinite period of time. No patients had then been randomized (included) in the study, but five patients had been through introductory interviews. One patient had according to Sudbø been subject to a surgical biopsy for assessment with a view to randomizing in the study.

The Commission has reviewed the NCI application and the material delivered by Jon Sudbø. The application is based on Sudbø’s raw material, which partly consists of fabricated data. There is nothing to indicate that any of the collaboration partners knew of or had any suspicion about this. Jon Sudbø also gives the impression that he can supply data and analyses, which, at least in retrospect, it is relatively obvious that he would not have been able to supply. He also states that he has received public permissions which are obviously fictitious. In this connection, the Commission refers in particular to page 130 of the application, where a series of essential points appear as pure fiction [the Commission’s running commentaries are included in square brackets]:

Accrual Infrastructure, Feasibility

Project 1 leader Dr. Sudbo and Core C Co-Leader Dr. Reith built over a 10-year period the infrastructure

that will support clinical Project 1 and its translational interactions with PO1 colleagues at M.D. Anderson

and Weill Medical College of Cornell University (Dr. Dannenberg).

1993-4: Access to biopsy specimens from all Norwegian pathological departments approved by

the Norwegian Cancer Registry (Kreftregisteret), Norwegian Data Protection Agency

(Datatilsynet), Norwegian Department of Health and Social Security (Sosial- og

helsedepartementet). [This appears in all essentials as pure fiction, cf section 4.2.]

May 1995: Access to Norwegian Cancer-Registry data for evaluating follow-up of 150 patients

with oral white patches. [The date should have been from the beginning of 1996, and the material referred to is partly manipulated and fabricated, cf section 4.2.7].

• ...

January 1997: Access to this information granted by the Regional Ethical Committee (Regional

Etisk Komité), Norwegian Data Protection Agency (Datatilsynet), and the Internal Advisory Board

at the Norwegian Radium Hospital (NRH). [All this is incorrect, cf 4.2.4]

January 1998: Permission from the Norwegian Data Protection Agency (Datatilsynet) to do

telephone interviews to get additional epidemiological information regarding smoking and alcohol

habits and comorbidity from persons in the study. [Incorrect, cf 4.2.4]

• ...

February 2003: Epidemiological data on NSAID effects obtained from The Norwegian Cancer

Registry and National Health Survey Project. [This is pure fiction.]

In this context should be noted that in the application, Jon Sudbø demonstrates that he has a full overview of the formal procedures which apply to this type of medical research projects.

While the raw data gradually took form through the cooperation with an obviously unsuspecting J. Jack Lee, Jon Sudbø started work on the article which subsequently was published in The Lancet. A draft article was first sent to New England Journal of Medicine, which rejected it twice. The Commission has not been given access to the referee opinions. The article was then finally published in The Lancet in October 2005, after having been through a so-called fast-track referee system. It is worth noting that one of the professional colleagues, who reviewed the article, was highly negative to its publication.

The main results that were subsequently published in the Lancet article44 are to be found in a power point presentation by Dr. Ernest Hawk of National Cancer Institute in the USA from a FDA hearing in the middle of February 2005.

On April 7, 2005, American health authorities (FDA) warned against cardiovascular side effects of non-selective NSAIDs. European health authorities were more reserved, and the Commission does not know of any changes to the guidelines having been made. According to the press, the Norwegian Medicines’

Agency is giving priority to the case, but as far as the Commission knows no changes have been made to the Norwegian guidelines.

On April 7, Aftenposten [a major Norwegian daily newspaper] spent half its first page to report that Ibux (ibuprofen) could lead to heart disease. On May 3, Jon Sudbø is supposed to have stated to Adresseavisen45 [another Norwegian daily newspaper] that he “had to triple check the data because he could not believe they were correct. But they are water tight.” Jon Sudbø is unable to understand this press coverage.

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