9 Dreadful Clinical Experiments That Failed
9 Dysfunctional And Terrible Clinical Trials. 9 Horrifically Botched Clinical Trials.
1. THE THALIDOMIDE TRAGEDY: LESSONS FOR DRUG SAFETY AND REGULATION
In a post-war era when sleeplessness was prevalent, thalidomide was marketed to a world hooked on tranquilizers and sleeping pills. At the time, one out of seven Americans took them regularly. The demand for sedatives was even higher in some European markets, and the presumed safety of thalidomide, the only non-barbiturate sedative known at the time, gave the drug massive appeal. Sadly, tragedy followed its release, catalyzing the beginnings of the rigorous drug approval and monitoring systems in place at the United States Food and Drug Administration (FDA) today.
Thalidomide first entered the German market in 1957 as an over-the-counter remedy, based on the maker’s safety claims. They advertised their product as “completely safe” for everyone, including mother and child, “even during pregnancy,” as its developers “could not find a dose high enough to kill a rat.” By 1960, thalidomide was marketed in 46 countries, with sales nearly matching those of aspirin.
Around this time, Australian obstetrician Dr. William McBride discovered that the drug also alleviated morning sickness. He started recommending this off-label use of the drug to his pregnant patients, setting a worldwide trend. Prescribing drugs for off-label purposes, or purposes other than those for which the drug was approved, is still a common practice in many countries today, including the U.S. In many cases, these off-label prescriptions are very effective, such as prescribing depression medication to treat chronic pain.
However, this practice can also lead to a more prevalent occurrence of unanticipated, and often serious, adverse drug reactions. In 1961, McBride began to associate this so-called harmless compound with severe birth defects in the babies he delivered. The drug interfered with the babies' normal development, causing many of them to be born with phocomelia, resulting in shortened, absent, or flipper-like limbs. A German newspaper soon reported 161 babies were adversely affected by thalidomide, leading the makers of the drug—who had ignored reports of the birth defects associated with the it—to finally stop distribution within Germany. Other countries followed suit and, by March of 1962, the drug was banned in most countries where it was previously sold.
In July of 1962, president John F. Kennedy and the American press began praising their heroine, FDA inspector Frances Kelsey, who prevented the drug’s approval within the United States despite pressure from the pharmaceutical company and FDA supervisors. Kelsey felt the application for thalidomide contained incomplete and insufficient data on its safety and effectiveness. Among her concerns was the lack of data indicating whether the drug could cross the placenta, which provides nourishment to a developing fetus.
She was also concerned that there were not yet any results available from U.S. clinical trials of the drug. Even if these data where available, however, they may not have been entirely reliable. At the time, clinical trials did not require FDA approval, nor were they subject to oversight. The “clinical trials” of thalidomide involved distributing more than two and a half million tablets of thalidomide to approximately 20,000 patients across the nation—approximately 3,760 women of childbearing age, at least 207 of whom were pregnant. More than one thousand physicians participated in these trials, but few tracked their patients after dispensing the drug.
The tragedy surrounding thalidomide and Kelsey’s wise refusal to approve the drug helped motivate profound changes in the FDA. By passing the Kefauver-Harris Drug Amendments Act in 1962, legislators tightened restrictions surrounding the surveillance and approval process for drugs to be sold in the U.S., requiring that manufacturers prove they are both safe and effective before they are marketed. Now, drug approval can take between eight and twelve years, involving animal testing and tightly regulated human clinical trials.
Despite its harmful side effects, thalidomide is FDA-approved for two uses today—the treatment of inflammation associated with Hansen’s disease (leprosy) and as a chemotherapeutic agent for patients with multiple myeloma, purposes for which it was originally prescribed off-label. Because of its known adverse effects on fetal development, the dispensing of thalidomide is regulated by the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.) program. The S.T.E.P.S. program, designed by Celgene pharmaceuticals and carried out in pharmacies where thalidomide prescriptions are filled, educates all patients who receive thalidomide about potential risks associated with the drug.
Thalidomide has also been associated with a higher occurrence blood clots and nerve and blood disorders. Northwestern University’s pharmacovigiliance team, Research on Adverse Drug Events And Reports (RADAR), has launched a joint project with the Walgreens pharmacy at Northwestern Memorial Hospital so that these side effects may be understood and monitored, like those affecting fetal development. RADAR, led by Dr. Charles Bennett of the Feinberg School of Medicine, combines the expertise of clinicians, academics, pharmacists, and statisticians to monitor and disseminate information about adverse drug reactions to cancer drugs.
Their project tracks the number of patients who get a blood clot after receiving thalidomide, whether or not the patient received an anticoagulant drug, which are used to help prevent clotting, and if so, which drug was used. Tracking this information will help researchers better identify the incidence and prevention of thalidomide-associated blood clots, allowing the drug to continue to serve as an effective therapy for many patients.
2. The soldier who unknowingly took part in a nerve gas test which killed him
In 1953, a young RAF airman, Ronald Maddison, died after being exposed to sarin at Porton Down in Wiltshire.
In the study, Maddison was told he was helping to find a cure for the common cold. He was offered 15 shillings and a three-day leave pass. He planned to use the money to purchase an engagement ring for his girlfriend, Mary Pyle.
Once in the facility, he was exposed to 200 milligrams of sarin nerve gas which was dropped onto a piece of uniform material wrapped around his arm. Within twenty minutes, he began to sweat and complained that he did not feel well. He soon slumped over the table. A few moments later, he complained of deafness and started gasping for breath and convulsing. He was taken to a nearby medical facility, where doctors attempted to resuscitate him before injecting adrenaline into his heart. Nothing worked.Less than 45 minutes after being exposed to the poison, he was pronounced dead.
3. Florida Clinic Blinds Three Patients in Botched ‘Clinical Trial’
An unproven stem cell therapy conducted by a Florida clinic has blinded three patients in an apparent clinical trial gone horribly wrong. The incident showcases the extent to which unscrupulous clinics will take advantage of desperate patients—and how the lack of government oversight contributes to the problem.
As reported in the New England Journal of Medicine, the clinical trial—if it can be called that—involved three women between the ages of 72 and 88 who were suffering from macular degeneration, a common progressive disease of the retina that leads to loss of vision. The women, all of whom were experiencing various degrees of vision loss, sought the help of a Florida clinic, which claimed to be testing a stem cell procedure designed to treat macular degeneration. Sometime in 2015, a week after stem cells were injected into their eyes, the women became blind. Two years later, doctors say there’s virtually no chance the women’s vision will be restored.
The authors of the new report, ophthalmologists Jeffrey Goldberg from Stanford University School of Medicine and Thomas Albini from the University of Miami, said the unfortunate incident serves as “a call to awareness for patients, physicians and regulatory agencies of the risks of this kind of minimally regulated, patient-funded research.”
Stem cells are undifferentiated cells that haven’t quite decided what they want to be when they grow up. Under the right conditions, these immature cells can be transformed into virtually any kind of cell found in the body, which is why they’ve proven useful in regenerative medicine.
Eventually, scientists hope to be able to use stem cells to regenerate damaged tissue and organs—and possibly even repair the effects of macular degeneration—but we’re not there yet. The only truly effective clinical application of stem cells to date has been in bone marrow transplants, in which stem cells extracted from a donor’s bone marrow are used to produce a fresh blood system for patients suffering from blood disorders such as leukemia. A recent study showed that there are nearly 600 clinics peddling unproven stem-cell procedures in the United States for a wide range of conditions, including arthritis, autism, cerebral palsy, stroke, muscular dystrophy, and cancer.
As noted in the NEJM report, two of the three patients learned about the stem cell trial for macular degeneration on ClinicalTrials.gov, a registry run by the US National Library of Medicine. The listings on this site aren’t fully scrutinized for scientific efficacy. The patients were reportedly under the assumption that they were participating in a bonafide clinical trial, but the consent form and other materials made no mention of a trial. Tellingly, each patient had to pay $5,000 for the procedure. This is highly unorthodox for a clinical trial, and it should have been cause for alarm. “I’m not aware of any legitimate research, at least in ophthalmology, that is patient-funded,” Albini said in a statement.
The NEJM study didn’t identify the Florida clinic responsible, but (conveniently) the authors provided the name of the trial: “Study to assess the safety and effects of cells injected intravitreal in dry macular.” A quick Google search calls the trial up, along with the name of the company responsible: Bioheart Inc., otherwise known as US Stem Cell. As the ClinicalTrials.gov page indicates, the study “has been withdrawn prior to enrollment.” According to Goldberg and Albini, the company is no longer performing the procedure, but it is still seeing patients.
The trial itself was a joke, lacking in all the components of a properly designed test. It wasn’t based on prior laboratory experiments, no control group was assigned, no data was collected, and no plans were made for follow-ups.
During the procedure, the patients had some of their fat cells (i.e. adipose tissue) removed, along with a standard blood withdrawal. The fat tissues were then processed with an enzyme to draw out stem cells. Once plasma was isolated from the blood and added to the stem cells, the mixture was injected into both eyes of each patient—yes, both eyes. Again, another serious clinical no-no; normally, only one eye would be injected for an experimental procedure like this in the event that something should go wrong. The entire procedure lasted less than an hour.
A week later, all three women were blind. As noted in the NEJM report, the blindness was accompanied by detached retinas and hemorrhaging.
The patients’ severe visual loss after the injection was associated with ocular hypertension, hemorrhagic retinopathy, vitreous hemorrhage, combined traction and rhegmatogenous retinal detachment, and lens dislocation. After one year, the patients’ visual acuity ranged from 20/200 to no light perception.
Goldberg and Albini say the preparation of the stem cells was likely shoddy, and the injections may have been contaminated. Once in the eye, the stem cells could have changed into myofibroblasts, a type of cell associated with scarring.
The Florida clinic, it would appear, was appealing to the desperation of their patients, while taking advantage of a regulatory loophole. As the authors write in their report:
Adipose tissue–derived “stem cells” have been increasingly used by “stem-cell clinics” because of the relative ease of obtaining and preparing these cells. Many of the clinics that provide these stem-cell therapies have done so under the auspices of patient-funded, institutional review board–approved research, and the research is listed on ClinicalTrials.gov without an investigational new drug filing with the FDA.
At the time, the procedure was not subject to FDA approval because the cells weren’t transferred between patients, and because the cells were considered “minimally processed.” The FDA has since revised its requirements, and it now needs approval for these types of procedures. In addition to updating its regulations, the FDA is also clamping down on stem cell clinics.
That’s obviously a good thing, but it’s a little too late for the women involved. This incident shows what happens when regulations and oversight are weak, and how shady companies will take risks with their patients’ health. Certainly food for thought as Trump and his cronies start to recreate the FDA in their own image.
Update: We reached out to US Stem Cell Clinic for comment and they responded with this statement:
Founded in 1999, U.S Stem Cell, Inc. has been committed to the research and development of effective cell technologies to treat patients with a variety of diseases and injuries. Since 2001, our clinics have successfully conducted more than 7,000 stem cell procedures with less than 0.01% adverse reactions reported. We are unable to comment further on specific cases due to patient confidentiality or legal confidentiality obligations. Neither US Stem Cell nor US Stem Cell Clinic currently treats eye patients.
4. Pfizer pays out to Nigerian families of meningitis drug trial victims
The parents of four Nigerian children who died of meningitis have become the first winners of a 15-year legal battle against Pfizer over a fiercely controversial drug trial.
The world's biggest research-based pharmaceutical company announced on Thursday that it had made payments of $175,000 (£108,000) to each family. More such compensation settlements are expected to follow.
Pfizer was sued after 11 children died in a clinical trial when the northern state of Kano was hit by Africa's worst ever meningitis epidemic in 1996. A hundred children were given an experimental oral antibiotic called Trovan, while a further hundred received ceftriaxone, the "gold-standard" treatment of modern medicine.
Five children died on Trovan and six on ceftriaxone. But later it was claimed that Pfizer did not have proper consent from parents to use an experimental drug on their children and questions were raised over the documentation of the trial.
Legal action filed against the company alleged that some received a dose lower than recommended, leaving many children with brain damage, paralysis or slurred speech.
US-based Pfizer had argued that meningitis and not its antibiotic had led to the deaths of 11 children and harm to dozens of others. But in 2009 it reached a tentative out-of-court settlement with the Kano state government worth $75m.
The families of four of the children each collected cheques for $175,000 from a compensation trust fund, after submitting DNA samples to show that the dead were their offspring.
The compensation was the first given out by the Healthcare/Meningitis Trust Fund. The decision over who is compensated and for how much is being managed by an independent board of trustees in Kano, not by the government or Pfizer, the company has said. "We are pleased that these four individuals, the first group of qualified claimants of the Healthcare/Meningitis Trust Fund, have received compensation," said a spokesman.
"This is the first step in a multiphase review process by which the independent board of trustees that manages the funds will deliver payments to all other claimants.
"We thank them for their commitment and dedication to seeing this process through in the most timely and transparent way possible."
But one parent who lost a daughter said the process was still dogged by local factionalism and he had no idea when he would receive money.
"I talked to my attorney this week," said the man, who did not wish to be named for legal reasons. "They are still in contact with Pfizer as to when I will get paid. We are just crossing our fingers."
He added: "We are fed up with this case. Our children are dead and some are maimed. We want to end this matter now, but some people are being opportunist for riches."
Pfizer said in February it had settled all outstanding lawsuits involving accusations that it tested the experimental antibiotic Trovan on children.
The pharmaceutical giant also agreed to sponsor health projects in Kano as well as creating a fund of $35m to compensate those affected.
But last year a US diplomatic cable uncovered by WikiLeaks revealed that Pfizer hired investigators to look for evidence of corruption against the Nigerian attorney general in an effort to persuade him to drop the legal action.
The cable reported a meeting between Pfizer's country manager, Enrico Liggeri, and US officials at the Abuja embassy on 9 April 2009. It stated: "According to Liggeri, Pfizer had hired investigators to uncover corruption links to federal attorney general Michael Aondoakaa to expose him and put pressure on him to drop the federal cases.
He said Pfizer's investigators were passing this information to local media."
There is no suggestion that the attorney general was swayed by the pressure. Pfizer, for its part, issued a statement at the time saying it had acted properly while negotiating its 2009 settlement with the government. "Although Pfizer has not seen any documents from the US embassy in Nigeria regarding the federal government cases," it said, "any notion that the company hired investigators in connection to the former attorney general is simply preposterous."
Pfizer had planned to sell Trovan in the US and Europe after the trials on African children. However, its licence was withdrawn in Europe because of concern over liver toxicity.
5. FDA suspends Juno clinical trial after 2 patient deaths
The Food and Drug Administration has suspended a clinical trial of a Juno Therapeutics treatment after two patients in the trial died last week.
The most likely factor behind the deaths was the addition of another cancer-fighting drug to the treatment regimen, Juno CEO Hans Bishop said in a conference call Thursday to discuss the suspension.
The FDA placed the so-called clinical hold on the trial on Wednesday, and Juno (Nasdaq: JUNO) disclosed it Thursday.
The trial suspension is a setback for the company, which is promoting its cancer therapies as next-generation treatments in the war on cancer.
“The hold will likely impact our ability to achieve our goal of getting approval of JCAR015 as early as 2017,” Bishop said, referring to FDA approval of the therapy.
The suspended trial is a Phase II, or mid-stage, clinical trial of Juno immunotherapy treatment JCAR015 in adult patients with with relapsed or refractory B cell acute lymphoblastic leukemia, known as r/r ALL.
Juno didn’t immediately respond to questions about what hospital the trial was held at or where the deaths occurred. Juno therapies have been used in trials at Memorial Sloan-Kettering in New York, as well as Seattle Children’s and the Fred Hutchinson Cancer Research Center in Seattle.
Juno said it has proposed to the FDA continuing the trial without using the cancer drug fludarabine that it had added to the pre-conditioning regimen. Instead it will use only cyclophosphamide in that regimen.
The company plans to submit to the FDA this week the documentation that the drug agency has requested, which includes a revised patient informed consent form, a revised investigator brochure, a revised trial protocol and a copy of the Juno presentation made to the agency Wednesday.
“The FDA have told us they will review these documents on an expedited basis,” Bishop said.
There was a death in the trial in May from the same condition, cerebral edema – a swelling in the brain that is the result of excessive fluid – that killed the two patients last week. Juno had decided at the time that death was due to a confluence of factors.
Juno issued its press release just after the close of the stock markets. It had finished the day up 2.2 percent at $40.82, but it was down more than 27 percent at one point in after-hours trading.
6. The 18-year-old victim of a gene therapy clinical trial that went wrong
18-year-old Jesse Gelsinger had a condition called ornithine transcarbamylase deficiency (OTC), but it was under control through a combination of diet and medication. He lacked a functional enzyme involved in breaking down ammonia, a waste product of protein metabolism that becomes toxic when its levels become too high. The disease is fatal in infants, but he had not inherited it. It was, for him, the result of a spontaneous genetic mutation after conception and was not as severe.
The otherwise healthy teen joined a clinical trial at the University of Pennsylvania aimed at developing a treatment for infants born with the disease. It was there he was injected with an adenoviral vector carrying a corrected gene to test the safety of the procedure. Four days later he passed away, after having suffered a massive immune response triggered by the use of the viral vector used to transport the gene into his cells, leading to multiple organ failure and brain death.
His 1999 death has since slowed progress in gene therapy for any condition.
7. 'IT WAS LIKE A HORROR MOVIE' Human guinea pigs disfigured by ‘Elephant Man drug trial’ tell of limb loss horror
SIX men who suffered horrific side effects in a drugs trial that went wrong a decade ago have spoken out in a new documentary.
In March 2006 eight men volunteered to try a new drug that researchers hoped would manipulate the immune system and significantly improve cancer treatment.
Instead, after taking the TGN1412 drug, six men were left writhing and screaming in agony as their organs started to fail, their heads began to swell which led many to vomiting in the hospital ward.
Several of them also had to have different parts of their body amputated at Northwick Park Hospital, London, during the testing phase which was soon dubbed the ‘Elephant Man’ drug trials.
Ryan Wilson, who was 21 when the trial started, had to spend four months in hospital during which his fingers and sections of his feet were amputated.
8. University of Minnesota Blasted for Deadly Clinical Trial
It’s not easy to cover up the circumstances around the violent death of a research subject in a botched university drug study. It’s even harder when the mutilated corpse of the subject is discovered in a blood-soaked bathroom in the middle of the night, the head almost completely severed from the body. Yet my employer, the University of Minnesota, managed to do just that for nearly eleven years, until two weeks ago, when the state’s Legislative Auditor delivered the results of an eight-month investigation into the case. The Auditor’s blistering report included evidence of coercion, conflicts of interest, a deeply flawed research oversight system and a series of false and misleading statements by university officials designed to prevent external scrutiny.
This story began in 2003, when Dr. Stephen Olson, a psychiatrist at the University of Minnesota used the threat of involuntary commitment to coerce a psychotic young man named Dan Markingson into the so-called “CAFÉ” study: an AstraZeneca-funded trial of antipsychotic drugs aimed at patients experiencing their first psychotic episode. His mother, Mary Weiss, objected to her son’s enrollment and tried desperately for months to get Dan out of the study, warning Olson and his co-investigator, Charles Schulz, that her son’s condition was deteriorating and that he was in danger of committing suicide. Her warnings were consistently ignored. On May 8, 2004, five months into the CAFÉ study, Dan died after trying to decapitate himself with a box-cutter.
The university managed to keep Dan’s violent death out of the public eye until 2008, when the scandal was reported by Paul Tosto and Jeremy Olson in the St. Paul Pioneer Press. When that report was ignored by university officials, I wrote about the case for Mother Jones. The study sponsor, AstraZeneca was in the process of settling a half-billion dollar federal fraud investigation, in which unsealed documents suggested that AstraZeneca was rigging, spinning and burying studies in order to market their antipsychotic drug, Seroquel. Some of those studies appeared to lead to the University of Minnesota. Specifically, they led to Charles Schulz, the Chair of the Department of Psychiatry and a well-compensated AstraZeneca consultant.
“Thus far, we have buried trials 15, 31, 56 and are considering COSTAR,” an AstraZeneca official wrote in 1999. “The larger issue is how do we face the outside world when they begin to criticize us for suppressing data.” As it turned out, the outside world would be brutally critical. In Mother Jones, I wrote about the role Schulz played in the self-described “smoke and mirrors job” that AstraZeneca performed on Study 15, a notorious trial that cast serious doubt on the efficacy of Seroquel and linked it to weight gain and diabetes. A year later, Andy Mannix of City Pages did the same with Schulz and the burial of Study 41, which showed an extended-release version of Seroquel to be no better than placebo.
The AstraZeneca study in which Dan Markingson died appeared to be little better. Psychiatric experts I spoke to called it a “non-study” with “very little value.” It appeared to be designed not to produce scientifically valid results, but rather to generate a positive marketing message for AstraZeneca. “It looks like an entirely marketing-driven exercise,” one expert said. This revelation raised a profoundly disturbing ethical question. As I wrote in 2010:
But what if a research study is not really aimed at producing genuine scientific knowledge at all? The documents emerging in litigation suggest that pharmaceutical companies are designing, analyzing, and publishing trials primarily as a way of positioning their drugs in the marketplace. This raises a question unconsidered in any current code of research ethics. How much risk to human subjects is justified in a study whose principal aim is to “generate commercially attractive messages”?
In the years since my article in Mother Jones appeared, University of Minnesota officials have consistently refused to look into the case or even discuss it. Instead, they have defended themselves by claiming that the case had been reviewed by a long list of internal and external bodies, all of which had exonerated the university. While this defense worked for years, it was almost completely untrue. According to the Legislative Auditor’s report, university officials “dismissed the need for further consideration for the Markingson case by making misleading statements about past reviews.” The report noted that this “insular and inaccurate response has seriously harmed the University of Minnesota’s credibility and reputation.”
In fact, the university’s credibility and reputation were already reeling. In February, an external review requested by the Faculty Senate blasted the university’s research protection system, writing that its failures and deficiencies raise “profound questions” about its ability to review studies adequately. The review described a “culture of fear” in the Department of Psychiatry, where panelists heard “stories of intimidation by researchers and fear of retaliation should staff voice opposition to practices that were of concern.” So damning was the external review that the consumer rights group Public Citizen immediately called for a federal investigation.
If anyone in the university administration has been chastened, they have not spoken up. At first President Eric Kaler tried to minimize the fallout, saying that was “particularly gratified — but not surprised” that the university’s hand-picked review panel had found “no legal or compliance violations.” That did not play well. So three weeks later, when the Legislative Auditor presented him with hard evidence of deliberate wrongdoing, Kaler responded by disputing the report, issuing a series of half-hearted apologies to Dan’s mother, Mary Weiss, and finally, with a straight face, claiming that no previous review had alerted the university to ethical breaches in the case.
In fact, to be unaware of these ethical breaches would have meant spending the past four years in a sound-proof bunker. The Markingson case has generated international condemnation. Hundreds of academic experts have called publicly for an investigation, including the editor of The Lancet and three former editors of The New England Journal of Medicine. The controversy has been reported by journals ranging from Science to the Medical Journal of Australia. A former governor of Minnesota, Arne Carlson, has become deeply involved in the case and met with Kaler personally to express his concern. Only a year ago, to mark the tenth anniversary of Dan Markingson’s death, activists interrupted a meeting of the Board of Regents to present Kaler with funeral flowers. University of Minnesota bioethicist Leigh Turner proceeded to lambaste the Board for its willful blindness. And now, four years into his administration, Kaler is shocked, shocked to discover that research misconduct is taking place.
Kaler and his management team have proposed a series of uncontroversial “initiatives” and “action plans” designed to deflect criticism. Last week, the Regents unanimously approved these plans at a public meeting that combined the best elements of a Soviet propaganda display and an amateur puppet show. One after one, the Regents affirmed their trust in President Kaler as a “president of great integrity” and their patriotic belief that medical research saves lives. If any of the Regents appreciated the gravity of the situation, they disguised it well. Faced with an eleven year cover-up, a mutilated corpse and a mother whose life has been utterly destroyed, Regent Linda Cohen responded by saying, “I am really proud of this university.”
The university’s only substantive concession has been to suspend new enrollment in psychiatric drug studies until the university can hire an “independent,” for-profit Institutional Review Board to review them. President Kaler has taken no action against the two psychiatrists most responsible for the debacle, Dr. Stephen Olson and his department chair, Dr. Charles Schulz. Nor has he done anything to make amends for the mistreatment of a second mentally ill subject whose experience at the hands of university psychiatrists was alarmingly similar to that of Dan Markingson. The university completed an internal investigation of that case nearly six months ago, but it is still refusing to make that investigation public.
Amid all the frenzy that has come with the Legislative Auditor’s report, a striking omission has gone largely unnoticed. The Legislative Auditor did not actually answer the question that he was asked. He was asked to investigate how many research subjects had died or been seriously injured in psychiatric research studies at the University of Minnesota, and what the circumstances were that led to those deaths and injuries. But the report he returned dealt only with a single case: that of Dan Markingson. The report did not explain why this larger question was left unanswered.
Of course, university leaders would like for everyone to forget the question was ever asked. They claim to be cleaning up the mess described in the report while pretending not to notice that their cover-up was the object of the report’s most scathing criticism. Yet without knowing how many deaths, injuries and coerced enrollments there have been, it will be impossible to move forward–not least because it will be impossible to know how far the cover-up extends.
9. French drug trial scandal: 'dogs died in pre-clinical test'
A drug that left one person dead and four others with suspected brain damage in a controlled trial had killed several dogs in a previous test, it has been claimed.
However, the laboratory involved and France’s drug safety agency say details of earlier testing of the molecule cannot be published because of industrial secrecy.
Le Figaro said it had information suggesting a pre-clinical trial of the drug had left “a number” of dogs dead and others with neurological damage.
When news of the incident was revealed, Marisol Touraine, the French health minister, said 108 people had taken part in the trial for Portuguese pharmaceutical company Bial at a French clinic in January. Ninety of them were given varying doses of the drug while the rest took a placebo.
Six male patients aged 28 to 49, who were in good health, were given the highest dose and fell ill.
One was declared brain-dead and died days after being given the drug. Four others were taken to hospital where neurological specialists discovered they had suffered “unusual” lesions to the “base of the cranium”. These had caused brain damage resulting in coordination and movement problems that specialists suggested could be irreversible.
The state prosecutor has opened an inquiry into how the trial was carried out. A preliminary report absolved Biotrial, Bial and the French drug safety agency Agence Nationale de Sécurité du Médicament (ANSM), which approved the trial, of wrongdoing.
Bial has published the protocol for the administration of the drug but refuses to divulge more information on pre-clinical trials.
François Peaucelle, director of Biotrial, said the death of the dogs was not significant. “The conclusions of this study were sufficiently clear and clean to rule out any particular ambiguity about proceeding with human tests,” Peaucelle told BFMTV.
Dominique Martin, director of ANSM, told Le Figaro: “We have given all information that we can, but there is an industrial property question here.”
Touraine has promised complete transparency on the study, which she said was a phase one clinical trial, in which healthy volunteers take the medication to “evaluate the safety of its use, tolerance and pharmacological profile of the molecule”.
Medical trials typically have three phases to assess a new drug or device for safety and effectiveness. Phase one entails a small group of volunteers and focuses only on safety. Phase two and three are progressively larger trials to assess the drug’s effectiveness, although safety remains paramount.
Testing had already been carried out on animals, including chimpanzees, starting in July, Touraine said in January.
Prof Stephen Senn, an expert in statistical methods used in drug testing for the NHS and head of the Luxembourg-based Clinical and Epidemiological Investigation Center, said the drug trial accident was “extremely worrying”.
He said hiding behind industrial secrets legislation was “not acceptable”.
“The principle behind industrial secrets is relevant, but it has to come after the general interest … we cannot accept that it’s more important to keep industrial secrets than to avoid further serious problems for patients taking part in other clinical trials. It’s important that results can be discussed by everyone,” Senn told Le Figaro.
1. THE THALIDOMIDE TRAGEDY: LESSONS FOR DRUG SAFETY AND REGULATION
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Thalidomide first entered the German market in 1957 as an over-the-counter remedy, based on the maker’s safety claims. They advertised their product as “completely safe” for everyone, including mother and child, “even during pregnancy,” as its developers “could not find a dose high enough to kill a rat.” By 1960, thalidomide was marketed in 46 countries, with sales nearly matching those of aspirin.
Around this time, Australian obstetrician Dr. William McBride discovered that the drug also alleviated morning sickness. He started recommending this off-label use of the drug to his pregnant patients, setting a worldwide trend. Prescribing drugs for off-label purposes, or purposes other than those for which the drug was approved, is still a common practice in many countries today, including the U.S. In many cases, these off-label prescriptions are very effective, such as prescribing depression medication to treat chronic pain.
However, this practice can also lead to a more prevalent occurrence of unanticipated, and often serious, adverse drug reactions. In 1961, McBride began to associate this so-called harmless compound with severe birth defects in the babies he delivered. The drug interfered with the babies' normal development, causing many of them to be born with phocomelia, resulting in shortened, absent, or flipper-like limbs. A German newspaper soon reported 161 babies were adversely affected by thalidomide, leading the makers of the drug—who had ignored reports of the birth defects associated with the it—to finally stop distribution within Germany. Other countries followed suit and, by March of 1962, the drug was banned in most countries where it was previously sold.
In July of 1962, president John F. Kennedy and the American press began praising their heroine, FDA inspector Frances Kelsey, who prevented the drug’s approval within the United States despite pressure from the pharmaceutical company and FDA supervisors. Kelsey felt the application for thalidomide contained incomplete and insufficient data on its safety and effectiveness. Among her concerns was the lack of data indicating whether the drug could cross the placenta, which provides nourishment to a developing fetus.
She was also concerned that there were not yet any results available from U.S. clinical trials of the drug. Even if these data where available, however, they may not have been entirely reliable. At the time, clinical trials did not require FDA approval, nor were they subject to oversight. The “clinical trials” of thalidomide involved distributing more than two and a half million tablets of thalidomide to approximately 20,000 patients across the nation—approximately 3,760 women of childbearing age, at least 207 of whom were pregnant. More than one thousand physicians participated in these trials, but few tracked their patients after dispensing the drug.
The tragedy surrounding thalidomide and Kelsey’s wise refusal to approve the drug helped motivate profound changes in the FDA. By passing the Kefauver-Harris Drug Amendments Act in 1962, legislators tightened restrictions surrounding the surveillance and approval process for drugs to be sold in the U.S., requiring that manufacturers prove they are both safe and effective before they are marketed. Now, drug approval can take between eight and twelve years, involving animal testing and tightly regulated human clinical trials.
Despite its harmful side effects, thalidomide is FDA-approved for two uses today—the treatment of inflammation associated with Hansen’s disease (leprosy) and as a chemotherapeutic agent for patients with multiple myeloma, purposes for which it was originally prescribed off-label. Because of its known adverse effects on fetal development, the dispensing of thalidomide is regulated by the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.) program. The S.T.E.P.S. program, designed by Celgene pharmaceuticals and carried out in pharmacies where thalidomide prescriptions are filled, educates all patients who receive thalidomide about potential risks associated with the drug.
Thalidomide has also been associated with a higher occurrence blood clots and nerve and blood disorders. Northwestern University’s pharmacovigiliance team, Research on Adverse Drug Events And Reports (RADAR), has launched a joint project with the Walgreens pharmacy at Northwestern Memorial Hospital so that these side effects may be understood and monitored, like those affecting fetal development. RADAR, led by Dr. Charles Bennett of the Feinberg School of Medicine, combines the expertise of clinicians, academics, pharmacists, and statisticians to monitor and disseminate information about adverse drug reactions to cancer drugs.
Their project tracks the number of patients who get a blood clot after receiving thalidomide, whether or not the patient received an anticoagulant drug, which are used to help prevent clotting, and if so, which drug was used. Tracking this information will help researchers better identify the incidence and prevention of thalidomide-associated blood clots, allowing the drug to continue to serve as an effective therapy for many patients.
2. The soldier who unknowingly took part in a nerve gas test which killed him
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In the study, Maddison was told he was helping to find a cure for the common cold. He was offered 15 shillings and a three-day leave pass. He planned to use the money to purchase an engagement ring for his girlfriend, Mary Pyle.
Once in the facility, he was exposed to 200 milligrams of sarin nerve gas which was dropped onto a piece of uniform material wrapped around his arm. Within twenty minutes, he began to sweat and complained that he did not feel well. He soon slumped over the table. A few moments later, he complained of deafness and started gasping for breath and convulsing. He was taken to a nearby medical facility, where doctors attempted to resuscitate him before injecting adrenaline into his heart. Nothing worked.Less than 45 minutes after being exposed to the poison, he was pronounced dead.
3. Florida Clinic Blinds Three Patients in Botched ‘Clinical Trial’
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As reported in the New England Journal of Medicine, the clinical trial—if it can be called that—involved three women between the ages of 72 and 88 who were suffering from macular degeneration, a common progressive disease of the retina that leads to loss of vision. The women, all of whom were experiencing various degrees of vision loss, sought the help of a Florida clinic, which claimed to be testing a stem cell procedure designed to treat macular degeneration. Sometime in 2015, a week after stem cells were injected into their eyes, the women became blind. Two years later, doctors say there’s virtually no chance the women’s vision will be restored.
The authors of the new report, ophthalmologists Jeffrey Goldberg from Stanford University School of Medicine and Thomas Albini from the University of Miami, said the unfortunate incident serves as “a call to awareness for patients, physicians and regulatory agencies of the risks of this kind of minimally regulated, patient-funded research.”
Stem cells are undifferentiated cells that haven’t quite decided what they want to be when they grow up. Under the right conditions, these immature cells can be transformed into virtually any kind of cell found in the body, which is why they’ve proven useful in regenerative medicine.
Eventually, scientists hope to be able to use stem cells to regenerate damaged tissue and organs—and possibly even repair the effects of macular degeneration—but we’re not there yet. The only truly effective clinical application of stem cells to date has been in bone marrow transplants, in which stem cells extracted from a donor’s bone marrow are used to produce a fresh blood system for patients suffering from blood disorders such as leukemia. A recent study showed that there are nearly 600 clinics peddling unproven stem-cell procedures in the United States for a wide range of conditions, including arthritis, autism, cerebral palsy, stroke, muscular dystrophy, and cancer.
As noted in the NEJM report, two of the three patients learned about the stem cell trial for macular degeneration on ClinicalTrials.gov, a registry run by the US National Library of Medicine. The listings on this site aren’t fully scrutinized for scientific efficacy. The patients were reportedly under the assumption that they were participating in a bonafide clinical trial, but the consent form and other materials made no mention of a trial. Tellingly, each patient had to pay $5,000 for the procedure. This is highly unorthodox for a clinical trial, and it should have been cause for alarm. “I’m not aware of any legitimate research, at least in ophthalmology, that is patient-funded,” Albini said in a statement.
The NEJM study didn’t identify the Florida clinic responsible, but (conveniently) the authors provided the name of the trial: “Study to assess the safety and effects of cells injected intravitreal in dry macular.” A quick Google search calls the trial up, along with the name of the company responsible: Bioheart Inc., otherwise known as US Stem Cell. As the ClinicalTrials.gov page indicates, the study “has been withdrawn prior to enrollment.” According to Goldberg and Albini, the company is no longer performing the procedure, but it is still seeing patients.
The trial itself was a joke, lacking in all the components of a properly designed test. It wasn’t based on prior laboratory experiments, no control group was assigned, no data was collected, and no plans were made for follow-ups.
During the procedure, the patients had some of their fat cells (i.e. adipose tissue) removed, along with a standard blood withdrawal. The fat tissues were then processed with an enzyme to draw out stem cells. Once plasma was isolated from the blood and added to the stem cells, the mixture was injected into both eyes of each patient—yes, both eyes. Again, another serious clinical no-no; normally, only one eye would be injected for an experimental procedure like this in the event that something should go wrong. The entire procedure lasted less than an hour.
A week later, all three women were blind. As noted in the NEJM report, the blindness was accompanied by detached retinas and hemorrhaging.
The patients’ severe visual loss after the injection was associated with ocular hypertension, hemorrhagic retinopathy, vitreous hemorrhage, combined traction and rhegmatogenous retinal detachment, and lens dislocation. After one year, the patients’ visual acuity ranged from 20/200 to no light perception.
Goldberg and Albini say the preparation of the stem cells was likely shoddy, and the injections may have been contaminated. Once in the eye, the stem cells could have changed into myofibroblasts, a type of cell associated with scarring.
The Florida clinic, it would appear, was appealing to the desperation of their patients, while taking advantage of a regulatory loophole. As the authors write in their report:
Adipose tissue–derived “stem cells” have been increasingly used by “stem-cell clinics” because of the relative ease of obtaining and preparing these cells. Many of the clinics that provide these stem-cell therapies have done so under the auspices of patient-funded, institutional review board–approved research, and the research is listed on ClinicalTrials.gov without an investigational new drug filing with the FDA.
At the time, the procedure was not subject to FDA approval because the cells weren’t transferred between patients, and because the cells were considered “minimally processed.” The FDA has since revised its requirements, and it now needs approval for these types of procedures. In addition to updating its regulations, the FDA is also clamping down on stem cell clinics.
That’s obviously a good thing, but it’s a little too late for the women involved. This incident shows what happens when regulations and oversight are weak, and how shady companies will take risks with their patients’ health. Certainly food for thought as Trump and his cronies start to recreate the FDA in their own image.
Update: We reached out to US Stem Cell Clinic for comment and they responded with this statement:
Founded in 1999, U.S Stem Cell, Inc. has been committed to the research and development of effective cell technologies to treat patients with a variety of diseases and injuries. Since 2001, our clinics have successfully conducted more than 7,000 stem cell procedures with less than 0.01% adverse reactions reported. We are unable to comment further on specific cases due to patient confidentiality or legal confidentiality obligations. Neither US Stem Cell nor US Stem Cell Clinic currently treats eye patients.
4. Pfizer pays out to Nigerian families of meningitis drug trial victims
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The world's biggest research-based pharmaceutical company announced on Thursday that it had made payments of $175,000 (£108,000) to each family. More such compensation settlements are expected to follow.
Pfizer was sued after 11 children died in a clinical trial when the northern state of Kano was hit by Africa's worst ever meningitis epidemic in 1996. A hundred children were given an experimental oral antibiotic called Trovan, while a further hundred received ceftriaxone, the "gold-standard" treatment of modern medicine.
Five children died on Trovan and six on ceftriaxone. But later it was claimed that Pfizer did not have proper consent from parents to use an experimental drug on their children and questions were raised over the documentation of the trial.
Legal action filed against the company alleged that some received a dose lower than recommended, leaving many children with brain damage, paralysis or slurred speech.
US-based Pfizer had argued that meningitis and not its antibiotic had led to the deaths of 11 children and harm to dozens of others. But in 2009 it reached a tentative out-of-court settlement with the Kano state government worth $75m.
The families of four of the children each collected cheques for $175,000 from a compensation trust fund, after submitting DNA samples to show that the dead were their offspring.
The compensation was the first given out by the Healthcare/Meningitis Trust Fund. The decision over who is compensated and for how much is being managed by an independent board of trustees in Kano, not by the government or Pfizer, the company has said. "We are pleased that these four individuals, the first group of qualified claimants of the Healthcare/Meningitis Trust Fund, have received compensation," said a spokesman.
"This is the first step in a multiphase review process by which the independent board of trustees that manages the funds will deliver payments to all other claimants.
"We thank them for their commitment and dedication to seeing this process through in the most timely and transparent way possible."
But one parent who lost a daughter said the process was still dogged by local factionalism and he had no idea when he would receive money.
"I talked to my attorney this week," said the man, who did not wish to be named for legal reasons. "They are still in contact with Pfizer as to when I will get paid. We are just crossing our fingers."
He added: "We are fed up with this case. Our children are dead and some are maimed. We want to end this matter now, but some people are being opportunist for riches."
Pfizer said in February it had settled all outstanding lawsuits involving accusations that it tested the experimental antibiotic Trovan on children.
The pharmaceutical giant also agreed to sponsor health projects in Kano as well as creating a fund of $35m to compensate those affected.
But last year a US diplomatic cable uncovered by WikiLeaks revealed that Pfizer hired investigators to look for evidence of corruption against the Nigerian attorney general in an effort to persuade him to drop the legal action.
The cable reported a meeting between Pfizer's country manager, Enrico Liggeri, and US officials at the Abuja embassy on 9 April 2009. It stated: "According to Liggeri, Pfizer had hired investigators to uncover corruption links to federal attorney general Michael Aondoakaa to expose him and put pressure on him to drop the federal cases.
He said Pfizer's investigators were passing this information to local media."
There is no suggestion that the attorney general was swayed by the pressure. Pfizer, for its part, issued a statement at the time saying it had acted properly while negotiating its 2009 settlement with the government. "Although Pfizer has not seen any documents from the US embassy in Nigeria regarding the federal government cases," it said, "any notion that the company hired investigators in connection to the former attorney general is simply preposterous."
Pfizer had planned to sell Trovan in the US and Europe after the trials on African children. However, its licence was withdrawn in Europe because of concern over liver toxicity.
5. FDA suspends Juno clinical trial after 2 patient deaths
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The most likely factor behind the deaths was the addition of another cancer-fighting drug to the treatment regimen, Juno CEO Hans Bishop said in a conference call Thursday to discuss the suspension.
The FDA placed the so-called clinical hold on the trial on Wednesday, and Juno (Nasdaq: JUNO) disclosed it Thursday.
The trial suspension is a setback for the company, which is promoting its cancer therapies as next-generation treatments in the war on cancer.
“The hold will likely impact our ability to achieve our goal of getting approval of JCAR015 as early as 2017,” Bishop said, referring to FDA approval of the therapy.
The suspended trial is a Phase II, or mid-stage, clinical trial of Juno immunotherapy treatment JCAR015 in adult patients with with relapsed or refractory B cell acute lymphoblastic leukemia, known as r/r ALL.
Juno didn’t immediately respond to questions about what hospital the trial was held at or where the deaths occurred. Juno therapies have been used in trials at Memorial Sloan-Kettering in New York, as well as Seattle Children’s and the Fred Hutchinson Cancer Research Center in Seattle.
Juno said it has proposed to the FDA continuing the trial without using the cancer drug fludarabine that it had added to the pre-conditioning regimen. Instead it will use only cyclophosphamide in that regimen.
The company plans to submit to the FDA this week the documentation that the drug agency has requested, which includes a revised patient informed consent form, a revised investigator brochure, a revised trial protocol and a copy of the Juno presentation made to the agency Wednesday.
“The FDA have told us they will review these documents on an expedited basis,” Bishop said.
There was a death in the trial in May from the same condition, cerebral edema – a swelling in the brain that is the result of excessive fluid – that killed the two patients last week. Juno had decided at the time that death was due to a confluence of factors.
Juno issued its press release just after the close of the stock markets. It had finished the day up 2.2 percent at $40.82, but it was down more than 27 percent at one point in after-hours trading.
6. The 18-year-old victim of a gene therapy clinical trial that went wrong
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The otherwise healthy teen joined a clinical trial at the University of Pennsylvania aimed at developing a treatment for infants born with the disease. It was there he was injected with an adenoviral vector carrying a corrected gene to test the safety of the procedure. Four days later he passed away, after having suffered a massive immune response triggered by the use of the viral vector used to transport the gene into his cells, leading to multiple organ failure and brain death.
His 1999 death has since slowed progress in gene therapy for any condition.
7. 'IT WAS LIKE A HORROR MOVIE' Human guinea pigs disfigured by ‘Elephant Man drug trial’ tell of limb loss horror
SIX men who suffered horrific side effects in a drugs trial that went wrong a decade ago have spoken out in a new documentary.
In March 2006 eight men volunteered to try a new drug that researchers hoped would manipulate the immune system and significantly improve cancer treatment.
Instead, after taking the TGN1412 drug, six men were left writhing and screaming in agony as their organs started to fail, their heads began to swell which led many to vomiting in the hospital ward.
Several of them also had to have different parts of their body amputated at Northwick Park Hospital, London, during the testing phase which was soon dubbed the ‘Elephant Man’ drug trials.
Ryan Wilson, who was 21 when the trial started, had to spend four months in hospital during which his fingers and sections of his feet were amputated.
8. University of Minnesota Blasted for Deadly Clinical Trial
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This story began in 2003, when Dr. Stephen Olson, a psychiatrist at the University of Minnesota used the threat of involuntary commitment to coerce a psychotic young man named Dan Markingson into the so-called “CAFÉ” study: an AstraZeneca-funded trial of antipsychotic drugs aimed at patients experiencing their first psychotic episode. His mother, Mary Weiss, objected to her son’s enrollment and tried desperately for months to get Dan out of the study, warning Olson and his co-investigator, Charles Schulz, that her son’s condition was deteriorating and that he was in danger of committing suicide. Her warnings were consistently ignored. On May 8, 2004, five months into the CAFÉ study, Dan died after trying to decapitate himself with a box-cutter.
The university managed to keep Dan’s violent death out of the public eye until 2008, when the scandal was reported by Paul Tosto and Jeremy Olson in the St. Paul Pioneer Press. When that report was ignored by university officials, I wrote about the case for Mother Jones. The study sponsor, AstraZeneca was in the process of settling a half-billion dollar federal fraud investigation, in which unsealed documents suggested that AstraZeneca was rigging, spinning and burying studies in order to market their antipsychotic drug, Seroquel. Some of those studies appeared to lead to the University of Minnesota. Specifically, they led to Charles Schulz, the Chair of the Department of Psychiatry and a well-compensated AstraZeneca consultant.
“Thus far, we have buried trials 15, 31, 56 and are considering COSTAR,” an AstraZeneca official wrote in 1999. “The larger issue is how do we face the outside world when they begin to criticize us for suppressing data.” As it turned out, the outside world would be brutally critical. In Mother Jones, I wrote about the role Schulz played in the self-described “smoke and mirrors job” that AstraZeneca performed on Study 15, a notorious trial that cast serious doubt on the efficacy of Seroquel and linked it to weight gain and diabetes. A year later, Andy Mannix of City Pages did the same with Schulz and the burial of Study 41, which showed an extended-release version of Seroquel to be no better than placebo.
The AstraZeneca study in which Dan Markingson died appeared to be little better. Psychiatric experts I spoke to called it a “non-study” with “very little value.” It appeared to be designed not to produce scientifically valid results, but rather to generate a positive marketing message for AstraZeneca. “It looks like an entirely marketing-driven exercise,” one expert said. This revelation raised a profoundly disturbing ethical question. As I wrote in 2010:
But what if a research study is not really aimed at producing genuine scientific knowledge at all? The documents emerging in litigation suggest that pharmaceutical companies are designing, analyzing, and publishing trials primarily as a way of positioning their drugs in the marketplace. This raises a question unconsidered in any current code of research ethics. How much risk to human subjects is justified in a study whose principal aim is to “generate commercially attractive messages”?
In the years since my article in Mother Jones appeared, University of Minnesota officials have consistently refused to look into the case or even discuss it. Instead, they have defended themselves by claiming that the case had been reviewed by a long list of internal and external bodies, all of which had exonerated the university. While this defense worked for years, it was almost completely untrue. According to the Legislative Auditor’s report, university officials “dismissed the need for further consideration for the Markingson case by making misleading statements about past reviews.” The report noted that this “insular and inaccurate response has seriously harmed the University of Minnesota’s credibility and reputation.”
In fact, the university’s credibility and reputation were already reeling. In February, an external review requested by the Faculty Senate blasted the university’s research protection system, writing that its failures and deficiencies raise “profound questions” about its ability to review studies adequately. The review described a “culture of fear” in the Department of Psychiatry, where panelists heard “stories of intimidation by researchers and fear of retaliation should staff voice opposition to practices that were of concern.” So damning was the external review that the consumer rights group Public Citizen immediately called for a federal investigation.
If anyone in the university administration has been chastened, they have not spoken up. At first President Eric Kaler tried to minimize the fallout, saying that was “particularly gratified — but not surprised” that the university’s hand-picked review panel had found “no legal or compliance violations.” That did not play well. So three weeks later, when the Legislative Auditor presented him with hard evidence of deliberate wrongdoing, Kaler responded by disputing the report, issuing a series of half-hearted apologies to Dan’s mother, Mary Weiss, and finally, with a straight face, claiming that no previous review had alerted the university to ethical breaches in the case.
In fact, to be unaware of these ethical breaches would have meant spending the past four years in a sound-proof bunker. The Markingson case has generated international condemnation. Hundreds of academic experts have called publicly for an investigation, including the editor of The Lancet and three former editors of The New England Journal of Medicine. The controversy has been reported by journals ranging from Science to the Medical Journal of Australia. A former governor of Minnesota, Arne Carlson, has become deeply involved in the case and met with Kaler personally to express his concern. Only a year ago, to mark the tenth anniversary of Dan Markingson’s death, activists interrupted a meeting of the Board of Regents to present Kaler with funeral flowers. University of Minnesota bioethicist Leigh Turner proceeded to lambaste the Board for its willful blindness. And now, four years into his administration, Kaler is shocked, shocked to discover that research misconduct is taking place.
Kaler and his management team have proposed a series of uncontroversial “initiatives” and “action plans” designed to deflect criticism. Last week, the Regents unanimously approved these plans at a public meeting that combined the best elements of a Soviet propaganda display and an amateur puppet show. One after one, the Regents affirmed their trust in President Kaler as a “president of great integrity” and their patriotic belief that medical research saves lives. If any of the Regents appreciated the gravity of the situation, they disguised it well. Faced with an eleven year cover-up, a mutilated corpse and a mother whose life has been utterly destroyed, Regent Linda Cohen responded by saying, “I am really proud of this university.”
The university’s only substantive concession has been to suspend new enrollment in psychiatric drug studies until the university can hire an “independent,” for-profit Institutional Review Board to review them. President Kaler has taken no action against the two psychiatrists most responsible for the debacle, Dr. Stephen Olson and his department chair, Dr. Charles Schulz. Nor has he done anything to make amends for the mistreatment of a second mentally ill subject whose experience at the hands of university psychiatrists was alarmingly similar to that of Dan Markingson. The university completed an internal investigation of that case nearly six months ago, but it is still refusing to make that investigation public.
Amid all the frenzy that has come with the Legislative Auditor’s report, a striking omission has gone largely unnoticed. The Legislative Auditor did not actually answer the question that he was asked. He was asked to investigate how many research subjects had died or been seriously injured in psychiatric research studies at the University of Minnesota, and what the circumstances were that led to those deaths and injuries. But the report he returned dealt only with a single case: that of Dan Markingson. The report did not explain why this larger question was left unanswered.
Of course, university leaders would like for everyone to forget the question was ever asked. They claim to be cleaning up the mess described in the report while pretending not to notice that their cover-up was the object of the report’s most scathing criticism. Yet without knowing how many deaths, injuries and coerced enrollments there have been, it will be impossible to move forward–not least because it will be impossible to know how far the cover-up extends.
9. French drug trial scandal: 'dogs died in pre-clinical test'
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However, the laboratory involved and France’s drug safety agency say details of earlier testing of the molecule cannot be published because of industrial secrecy.
Le Figaro said it had information suggesting a pre-clinical trial of the drug had left “a number” of dogs dead and others with neurological damage.
When news of the incident was revealed, Marisol Touraine, the French health minister, said 108 people had taken part in the trial for Portuguese pharmaceutical company Bial at a French clinic in January. Ninety of them were given varying doses of the drug while the rest took a placebo.
Six male patients aged 28 to 49, who were in good health, were given the highest dose and fell ill.
One was declared brain-dead and died days after being given the drug. Four others were taken to hospital where neurological specialists discovered they had suffered “unusual” lesions to the “base of the cranium”. These had caused brain damage resulting in coordination and movement problems that specialists suggested could be irreversible.
The state prosecutor has opened an inquiry into how the trial was carried out. A preliminary report absolved Biotrial, Bial and the French drug safety agency Agence Nationale de Sécurité du Médicament (ANSM), which approved the trial, of wrongdoing.
Bial has published the protocol for the administration of the drug but refuses to divulge more information on pre-clinical trials.
François Peaucelle, director of Biotrial, said the death of the dogs was not significant. “The conclusions of this study were sufficiently clear and clean to rule out any particular ambiguity about proceeding with human tests,” Peaucelle told BFMTV.
Dominique Martin, director of ANSM, told Le Figaro: “We have given all information that we can, but there is an industrial property question here.”
Touraine has promised complete transparency on the study, which she said was a phase one clinical trial, in which healthy volunteers take the medication to “evaluate the safety of its use, tolerance and pharmacological profile of the molecule”.
Medical trials typically have three phases to assess a new drug or device for safety and effectiveness. Phase one entails a small group of volunteers and focuses only on safety. Phase two and three are progressively larger trials to assess the drug’s effectiveness, although safety remains paramount.
Testing had already been carried out on animals, including chimpanzees, starting in July, Touraine said in January.
Prof Stephen Senn, an expert in statistical methods used in drug testing for the NHS and head of the Luxembourg-based Clinical and Epidemiological Investigation Center, said the drug trial accident was “extremely worrying”.
He said hiding behind industrial secrets legislation was “not acceptable”.
“The principle behind industrial secrets is relevant, but it has to come after the general interest … we cannot accept that it’s more important to keep industrial secrets than to avoid further serious problems for patients taking part in other clinical trials. It’s important that results can be discussed by everyone,” Senn told Le Figaro.
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