Conflicting Health Ministry Reports Accuse, Absolve Teva in Patient Experiments

An internal report contradicts the findings of a ministry panel of inquiry, which determined there was no scientific basis for tests done on multiple sclerosis patients at Ichilov

Teva Pharmaceuticals and Ichilov Hospital were recently absolved of charges earlier attributed to them by a Health Ministry commission of inquiry. The report absolving them, released by ministry ombudsman Prof. Haim Hershko, was in fact forwarded to the ministry's director general some 18 months ago, but its existence only recently came to light.

In July 2006, trials began in six countries (including Israel ) on Copaxone - Teva's leading drug for the treatment of multiple sclerosis. In Israel, tests were conducted on 13 multiple sclerosis patients in the neurology department of Tel Aviv's Ichilov Hospital.

Three months after that study at Ichilov began, Prof. Michal Schwartz, a scientist at the Weizmann Institute of Science who was engaged in preliminary studies with mice, contacted Teva with a warning. The dosages of the drug being administered to multiple sclerosis patients (a double daily dose ) may be harmful, she told them. In May 2007, Schwartz again warned Teva executives of the dangers she perceived.

Later on, her findings were sent to the director of the multiple sclerosis clinic of Ichilov, Dr. Vivian Drori, who had enlisted and treated the patients being used in the trials. At this stage, the option of sending the patients a letter in which they would be updated on medical developments was considered, but at Ichilov and Teva it was decided that such a letter would not be sent.

After about a month, the story was disclosed in the media and created a stir. The Health Ministry began investigating complaints filed by the patients who'd participated in the tests, who claimed the information about previous studies using mice had been concealed from them. After the story was exposed, four Israeli patients stopped their treatment with Copaxone.

The original commission of inquiry, headed by the president of the bioethics committee at Hadassah Hospital, Prof. Jacques Michel, wrote in its report that it had not been presented with convincing proof of Copaxone's effectiveness during the trial stage on animals, which preceded the trials conducted on human patients.

"The multiple sclerosis patients participating in the study are at risk. Apart from the possibility that the experimental treatment will hasten the progress of their disease, there is the possibility that their quality of life will be worsened as well," the inquiry panel wrote. The report indeed states that no damages to the participants of the Copaxone tests were indicated, but the committee also determined that it is not possible to ascertain whether or not the drug had harmed patients, as there was no follow up conducted of their condition after a year.

"There was no clear scientific or safety basis for conducting the trial, and the consent form was formulated in a vague fashion," the report stated. The committee also criticized Dr. Drori's handling of the trials, stating she acted "as one whose first obligation is to the company conducting the trials, and not the participants in it."

Teva was also criticized by the panel and it was further determined that the company could have conducted its tests on humans using smaller doses than what was actually decided on.

Report, counter report

The inquiry committee's report was signed in April 2009 and sent to the Health Ministry's ombudsman for review. A month later appeals of the findings were submitted to the ministry as well. It recently came to light that, in an unusual step, the ombudsman decided to form a new team, which he would head, and to write an additional report rejecting the accusations against Teva and Ichilov.

That team's report, sent to the Health Ministry director general in June 2009, just two months after the original report, stated "there are weak points that severely undermine the conclusions and recommendations of the inquiry committee." The new team criticized the previous panel, which did not note in its findings that the drug trials had received approval in Europe. According to the new team, the original commission of inquiry "sharply criticized the scientific and safety basis of the study, but ignored important data that supported its planning."

The two reports were brought to the attention of the director general of the Health Ministry at the time, Dr. Avi Yisraeli, but in a closed process, without the ministry declaring which set of findings it supports.

This past January, three patients who had participated in the study sued Teva, Ichilov Hospital and Health Ministry officials. Evidence in the case is currently being submitted by all parties, with a hearing set in another week and a half in the Petah Tikvah District Court. Hershko's report was included among the documents submitted by Teva.

The chairman of the original commission of inquiry approached the Health Ministry's current director general, Dr. Roni Gamzu, requested that an investigation be conducted to determine how the second report was leaked to Teva. He claims that it is an internal report, intended solely for the previous director general. Gamzu made it clear that he cannot discuss the matter due to a conflict of interests: Until recently he served as deputy director of Ichilov Hospital.

"The fact that Teva is trying to use a document that should not have ever been in its possession is a very serious matter," says Michel. "The transfer of the document is contrary to arrangements made with the Health Ministry's director general at the time."

The attorney representing the patients filing suit, Ahuva Ticho, recently contacted the ministry, requesting that Hershko's actions be investigated. "As far as we are concerned, the problem is that the commission of inquiry did its job, gathered testimony from the people involved and issued a grounded and signed report. But the Ministry of Health's ombudsman is portraying himself as an investigative body and issued a report that contradicts the original panel's findings - without gathering testimony and without any legal basis," says Ticho.

A comprehensive hearing

The ministry issued the following response: "In the wake of the reports submitted to the [former] Ministry of Health director general, Prof. Yisraeli conducted a comprehensive hearing on the treatment of multiple sclerosis patients. Yisraeli instructed the relevant health officials to [stay within the limits of] the authorities they are granted regarding clinical trials."

It was further stated that "Teva and the Ichilov Hospital administration were asked to convey to the participants in the trials, or to their families, the results of the study. Teva was also asked to convey to the Health Ministry any information it possessed regarding suits or investigations in the other countries participating in the tests. The lead investigator provided explanations regarding her actions at every stage of the study, including the delay in forwarding the information to the patients. All the directives were carried out."

Teva and Ichilov Hospital officials opted not to comment on the matter.