Deadly Side Effects New Details Emerge in East German Drug Test Scandal
Part 3: The Role of Doctors
Ulrich Moebius, a doctor who went from being a pharmaceutical manager to a critic of the industry after the Contergan affair, characterizes these tests as a crime. "They could have killed people," he says. Bayer rejects the accusations, saying that East German physicians were the ones who proposed the tests.
Severely depressed East German citizens were also used in drug trials. Instead of treating patients in acute phases with drugs with demonstrated efficacy in treating their disease, Charité doctors used them to test two antidepressants known for their severe side effects, levoprotyline and Ludiomil. The trial was done of behalf of Swiss firm Ciba-Geigy, which is now part of Novartis. Moebius, the co-founder of arznei-telegramm, a German medical journal critical of the pharmaceutical industry, classifies levoprotyline as one of the so-called dirty drugs. The East German tests would not have been possible in Western countries he says.
But the East German clinical investigators running the trial almost never detected problems with the patient trials, either because they could not or would not recognize them. In response to the sudden cardiac death of a patient who had participated in a trial involving Roche's drug carvedilol in 1989, they merely concluded that the patient's death was to be "classified as an event possible within the context of his illness." What exactly happened was never determined.
Could the physicians involved at GDR hospitals have recognized the dangers of the drug trials? Should they have opposed the Socialist Unity Party (SED) officials' deals with the Western pharmaceutical industry, and should they done more to protect the interests of their patients?
Harald Mau developed the pediatric surgery department at Charité, which he headed until 1983. He later become director of pediatric surgery and eventually was named dean of the hospital. Few people are as familiar with Berlin's largest hospital.
The dictatorial system left research directors and medical directors with no alternatives, he says. "One mistake, or one objection, and they would no longer have enjoyed the benefits resulting from the pharmaceutical testing," says Mau, who retired four years ago. Some gave and others took, he explains, and those who didn't participate with sufficient enthusiasm faced the wrath of their colleagues, because their lack of cooperation translated into the loss of benefits for their respective departments.
'It Brings In Hard Currency, So We'll Do It!'
"If we were lucky, the proceeds went directly to the department, and instruments could be purchased. If things didn't go well, the clinic kept the money or it was spent at the Charité level," says Mau. In the context of the competitive socialist system, the hospital administration would announce, at the end of each year, the amount of deutsche marks each department had earned. This meant that doctors who conducted the studies for Western companies were constantly under pressure to acquire hard currency in competition with one another. Mau remembers a sentence often uttered by senior physicians at Charité at the time: "It brings in hard currency, so we'll do it!"
Mau himself conducted clinical trials with antibiotics in his pediatric ward. "Everyone knew that when a new narcotic or a new sedative was coming, we would try it out, all in the context of 'testing,'" says Mau. Hospital staff documented the drugs' effects on patients for the Western pharmaceutical companies. The study protocols clearly defined how often they were to take various readings, including blood pressure and lipid and cholesterol levels.
Everything was done in a strictly hierarchical manner, and providing doctors with insights into the system frowned upon. The medical director at Charité passed on the orders to conduct trials to the clinic directors, who in turn notified the department heads. The drugs were always supplied through the hospital pharmacy, where they were treated like gold. The doctors were told: "We have received a Western drug, and you now have the opportunity to use it." But they were also expected to carefully document everything, which they were told was Charité's contribution in return for receiving the drugs.
The surgeons, neurologists and pediatricians working in the wards were given pills, as if out of thin air, without being told the circumstances under which they had made it across the Berlin Wall. "No one knew what agreements had been signed, and with whom," says Mau.
All of this was kept from patients, who were inadequately informed about the risks and side effects of the drugs being tested on them. A written informed consent was viewed as unnecessary.
Issues related to informed consent were handled by the SED medical officials, in direct coordination with the drug makers. In the case of Hoechst, for example, the company expressly declared in 1989 that it agreed with "information about the drugs remaining with the investigator and not being given to the patient."
This statement appears in the minutes of a meeting between Hoechst managers and an East German representative in Frankfurt on March 6, 1989. "The patient's consent is documented by the signatures of the treating physician and one witness," the document also reads. A comparable approach would have been inconceivable in West Germany. The company did not respond specifically to questions about the case.
Extremely Awkward Insights for Drug Makers
Such insights into their past are extremely awkward for the drug makers, which, following a wave of mergers, have mutated into giant global corporations. They don't coincide with the preferred self-image of an industry that pledges to uphold exemplary ethical standards. "In every clinical trial, the safety of participants is more important than anything else," writes the VFA in a statement. "We are responsible not only to ourselves, but to the entire world," Bayer HealthCare avers in its Global Guidelines.
The companies are especially confident when it comes to one issue: The human trials in East Germany were also done strictly according to protocol. Pfizer, the world's largest pharmaceutical company, which acquired Mack Illertissen, a company that had ordered many clinical trials on the other side of the Berlin Wall, insists that it is "not aware of any information on these issues."
Bayer also believes that everything was done by the book, says a spokesman. "At Bayer, all clinical trials were conducted and still are conducted in accordance with uniform global standards." Officials at Boehringer Ingelheim claim to be aware of only three studies conducted in the former East Germany, even though records indicate that there were at least twice as many.
Even the German government has done little to clear up this particularly dirty chapter of inter-German relations. But this is especially relevant, because the drugs tested in the GDR were later approved by the West German Federal Health Office, which was part of the Health Ministry. "Everyone at the Federal Health Office knew that Western companies were conducting clinical trials in East Germany," says Peter Schönhöfer, who headed the Office's department for post-approval drug safety until 1982. "No one ever asked why or how."
And yet there were high-level political talks on inter-German cooperation in medicine. For instance, records show that when West German Health Minister Rita Süssmuth (CDU) met with her East German counterpart, Mecklinger, she stated in a private conversation that West Germany had a special interest in "cooperation in scientific research."
Klaus Jürgen Henning, who in the 1980s was the spokesman for the Federal Health Office, which reported to Süssmuth, says today that when it came to drug licensing, West German officials had no concerns about studies done at East German hospitals, and that they were treated as the equivalent of West German studies. A spokesperson for Süssmuth says that she "was too unfamiliar with the issue" and that she could provide no "detailed information about trials in the GDR."
Time of the Essence for Researching Trials
The recent debate over the use of forced prison labor in East Germany shows that avoiding and ignoring the mistakes of the past isn't the only approach. In March, the Union of Associations for Victims of Communist Tyranny launched a research project on the issue in March. The effort is funded by furniture retailer IKEA, which had some of its products, including the Billy line of bookshelves, manufactured in East German prisons.
Germany isn't nearly as far along when it comes to addressing the pharmaceutical trials. Volker Hess, a medical historian, is finally interviewing contemporary witnesses at Charité and wants to see the archives completely declassified, so that researchers can identify the perpetrators and the victims. A two- to three-year research project would be needed, says Hess, although, as he notes, the VFA hasn't been willing to provide any funding for the effort yet.
Time is of the essence, because of the risk of important evidence of the human trials being lost. As part of regular housecleaning, Charité is in the process of destroying its files from 1983. In an old warehouse in Berlin's Tempelhof district, forklifts are currently transporting boxes of records to be destroyed.
Translated from the German by Christopher Sultan