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Big Pharma’s Role in Clinical Trials

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Pharmaceutical companies are the top sponsors of clinical trials, the best process for determining the safety and efficacy of drugs. Big Pharma funded clinical trials frequently result in publication bias, buried results and misleading information.

The pharmaceutical industry is the biggest funder of clinical trials in the U.S., but there is little financial incentive for Big Pharma to be honest about trial results.

In the multi-billion dollar industry, companies face pressures from shareholders looking for returns on investments, competitors racing to be the first to develop new treatments, and astronomical costs for researching and developing products.

The clinical trial process is the leading tool for evidence-based research to prove the safety and efficacy of treatments. It’s also an enormously expensive process. It costs millions of dollars to research and develop new treatments.  The industry spends more than $30 billion every year on drug development.

The low success rate of developmental drugs makes things more complicated. An estimated 30 percent of drugs don’t make it out of development to the first phase of clinical trials, and only 20 percent of those drugs make it to the first trial phase.

When all of the factors come together, the system creates an environment in which researchers misrepresent findings, design biased studies and put money ahead of patient safety.

Making matters worse, the medical community desperately relies on Big Pharma to fund trials searching for cures to hard-to-treat diseases and conditions. Unfortunately, there isn’t enough private or government funding available to develop drugs that the public needs without money from the industry.

Big Pharma funds 60 percent of all clinical trials, and it takes advantage of its power to persuade researchers and influence institutions.  The result is an under-informed and misinformed medical community giving advice to patients with false or incomplete data. The byproducts of industry cover-ups are scores of deaths and millions of dollars in industry profits.

How Publication Bias Kills People

Publication bias is one of the top obstacles to safety facing the healthcare industry and evidence-based medicine. The term refers to the phenomenon in which studies with positive results have a higher chance of being published than those with negative results.

Since 1948, researchers completed an estimated one million clinical trials, but they reported only half of those results. The numbers do not account for clinical trials that were terminated before they were completed.

There are a number of reasons why publication bias occurs.

  • Researchers publish positive findings more often than negative findings as a result of human bias. Scholars want their work to contribute to medical advancement and not deter it.
  • Researchers do not want to put the time and energy into writing studies about negative results.
  • Journals seek positive results and publish them more quickly to increase publicity.
  • Trial sponsors want to publish positive results to increase profit.

Publication bias endangers the public because clinical trial results that indicate a drug is dangerous or ineffective are withheld from the medical community. Doctors rely on published studies to make medical decisions. Without proper knowledge, or with incomplete information, doctors can unknowingly prescribe dangerous treatments to patients.

A perfect example is the history of the antiarrhythmic drug Lorcainide. Antiarrhythmic drugs suppress abnormal heart rhythms. In an early clinical trial in 1980, nine times as many patients died on Lorcainide than they did on a placebo – a harmless pill with no active ingredients. The manufacturer stopped the drug’s development for commercial reasons, and the researchers never published the study.

Other companies developed similar antiarrhythmic drugs, and doctors prescribed them to patients after heart attacks. Throughout the 80s, an estimated 20,000 to 75,000 people died every year from Lorcainide. In 1993, the researchers published the study results, and the drug was removed from the market. If the researchers published the study sooner, thousands of lives might have been saved.

The danger that publication bias presents to medical safety is clear, but it also threatens the foundation of clinical trials. Participants trust that the risks they subject themselves to during trials are for the advancement of medicine. When researchers do not publish the results of the trial, they break the trust they had with their participants because no advancement occurs.

Valuable resources are lost when scholars unknowingly duplicate trials. Researchers studying a treatment do not always know if that treatment has been studied before. They sometimes waste time and money repeating studies that were never published.

Of course, one solution to the problem would be to require researchers to publish the results of every trial. However, the Pharmaceutical Research and Manufacturers of America (PhRMA) refused to agree to publish every trial, and the industry rejected guidelines to reduce publication bias.

Realizing the need for better publication practices, the federal government mandated that trials regarding serious or life-threatening diseases be published on ClinicalTrials.gov, the government’s clinical trial database. However, studies indicate researchers don’t adhere to the mandate.

Publication bias includes unintentional biases among researchers and journal publishers, but some pharmaceutical companies intentionally mislead the medical world.

Big Pharma’s Clinical Trial Cover-Ups

Big Pharma has a long history of hiding negative clinical trial results. Unfortunately, lawsuits and whistleblowers rarely uncover results in time to prevent harmful consequences from occurring.

Cochrane Collaboration Reveals Tamiflu Trials

Governments spent billions of dollars stockpiling the influenza drug Tamiflu (oseltamivir) to protect against a major flu outbreak.

However, rare reports of suicidal thoughts and actions in children using Tamiflu raised concern. The Cochrane Collaboration, a nonprofit organization based in London that reviews health care information, began an investigation into the drug’s clinical trial results.

The organization requested the results of an estimated 36 trials involving Tamiflu, but the drug’s manufacturer only agreed to provide 10. After five years of negotiations and Freedom of Information Act requests, Cochrane finally received access to more than 70 studies and 100,000 pages of unpublished reports.

Cochrane discovered many of the trials produced negative or inconclusive results. Cochrane concluded that Tamiflu only shortened symptoms of influenza by one day and it did not prevent hospitalizations or complications from influenza.

Big Pharma Designed Atypical Trials for Success

Big Pharma can also skew trial results by designing them in certain ways that make them look successful.

The American Journal of Psychiatry found that 90 percent of 32 clinical trials for atypical antipsychotics resulted in positive findings for the companies that sponsored them. The analysis found companies designed trials to be favorable by slanting dosages of a competing drug or standard treatment. The researchers gave participants doses of competing drugs that were  too low or too high to be effective.

A former editor of the British Medical Journal, Richard Smith, wrote, “The companies seem to get the results they want not by fiddling the results, which would be far too crude and possibly detectable by peer review, but rather by asking the right questions.”

Manufacturer AstraZeneca possesses one of the worst reputations for skewing trial results. Dr. Melissa DelBello led one of the most influential studies financed by AstraZeneca on atypical antipsychotics.

Of the 30 adolescents diagnosed with bipolar disorder in DelBello’s study, 15 took the anti-seizure drug Depakote. The other 15 took Seroquel and Depakote. Only eight of the participants taking Seroquel finished the trial. DelBello originally stated the study was inconclusive, but she and her team later published the study claiming a combination of Seroquel and Depakote was more effective than Depakote alone.

The study led to a recommendation by an advisory board that atypical antipsychotics be a first-choice treatment in children with bipolar disorder. Three out of the four doctors on the panel received funding from pharmaceutical companies that manufacture atypicals. DelBello also received money from Big Pharma, about $238,000 from AstraZeneca during a three-year period.

Internal documents produced in one court case revealed damning information against AstraZeneca. A company sales representative stated: “Thus far, we have buried trials 15, 31, 56. The larger issue is how do we face the outside world when they begin to criticize us for suppressing data.”

The company paid $647 million in lawsuit settlements for failing to inform the public of Seroquel’s side effects.

GSK’s Concealment of Paxil Trials

In another example of trial data concealment, the U.S. Department of Justice accused GlaxoSmithKline of reporting false data from one clinical trial and hiding the data from two other trials involving the antidepressant Paxil.

One leaked company document stated, “it would be commercially unacceptable to include a statement that efficacy had not been demonstrated,” in one of the trials. The company falsely reported trial results, claiming Paxil was effective at treating children with depression. GSK eventually settled the claims for $3 billion, along with other claims for illegally marketing various drugs.

Pharmaceutical companies harm the public when they hide or misrepresent clinical trial data. Unethical behavior during clinical trials can also harm participants.

The University of Minnesota and Dan Markingson

The case of Dan Markingson and the University of Minnesota is one of the most-covered cases of a death during a Big Pharma clinical trial.

Markingson’s mother, Mary Weiss, aggressively protested her son’s involvement in a clinical trial funded by AstraZeneca at the university for more than a year. Her son eventually committed suicide during the trial despite Weiss’s attempts to have him seek other treatment options.

The author of a series of articles covering the event, Minnesota bioethics professor Carl Elliott, wrote: “The danger lies not just in the particular circumstances that led to Dan’s death, but in a system of clinical research that has been thoroughly co-opted by market forces, so that many studies have become little more than covert instruments for promoting drugs.”

The story began when Weiss went to visit her son in California. He moved west after graduating from the University of Michigan. She found her son had changed his last name to Markingson, was paranoid and suffering from delusions. She called police, but they did not find sufficient evidence to commit him to a mental institution.

Months later, Weiss convinced Markingson to move back home to Minnesota. He became increasingly violent and threatened to kill people, including Weiss. She called police, and he was taken to the University of Minnesota Academic Health Center. There, Dr. Stephen Olson treated him with Risperdal for bipolar disorder and schizophrenia. Olson recommended he be committed involuntarily to a mental institution because he “lacked the capacity to make decisions regarding such treatment.” Another doctor came to the same conclusion.

Then Olson had a change of heart on Markingson’s mental capacity. A week after saying he wasn’t capable of making decisions on his own, Olson enrolled Markingson in a clinical trial called the CAFE study. As part of the enrollment, Markingson consented – or made a decision on his own – to participate.

The trial required Markingson remain on a test drug, later revealed as Seroquel, even if it didn’t work. Researchers designed the study to support the efficacy of Seroquel. Only 119 of the original 400 participants finished the study, making findings statistically insignificant.

Weiss protested her son’s participation in the study, asking Olson to remove him. Olson refused. Throughout the study, Weiss and social workers reported Markingson’s condition was worsening, but Olson did not respond. Instead, the researcher recommended extending Dan’s stay of commitment, conveniently just long enough to complete the trial.

Weiss sent multiple letters to Olson and the chair of the psychiatry department, Dr. Charles Schulz, raising concern about Markingson’s condition. Despite his mother’s efforts to have him seek non-experimental treatment, Dan Markingson committed suicide during the clinical trial.

A massive cover-up followed.

The university’s Institutional Review Board (IRB), which is meant to protect participants, never formally investigated Markingson’s death. The IRB’s website stated its purpose was to “protect the rights and welfare of human research subjects.” However, IRB officials testified its purpose was not to protect participants, but to make sure researchers had a plan to protect participants.

One top IRB official, Richard Bianco, claimed there was no evidence of misconduct in the Markingson case. He later admitted that the 8,000 human studies at Minnesota were worth about $15 million. The psychiatry department made more than $15,000 for every participant who completed the CAFE study, giving it a financial incentive to keep participants in the trial despite risks. The department made more than $300,000 from the CAFE study.

Weiss filed an ethical complaint against Olson, but an independent expert dismissed it. A later investigation revealed the independent expert had numerous conflicts of interest, including serving on the IRB during Markingson’s trial and accepting money from AstraZeneca in the past. He made more than $83,000 from AstraZeneca in one year alone.

Most of Weiss’s attempts at seeking justice for Markingson’s death failed.

  • An FDA report exonerated the university from any guilt involving Markingson’s death.
  • Weiss filed a lawsuit against Minnesota, Olson and Schultz. The judge dismissed it, stating the IRB had a discretionary approval function which protected it from liability.
  • Weiss filed a lawsuit against AstraZeneca. The judge dismissed it, stating the company was not obliged to put the participant’s interests ahead of the company’s interests.
  • Weiss filed a malpractice suit against Olson, but the parties settled the suit for $75,000. Weiss claimed the settlement wasn’t enough to cover the costs she incurred while trying to take the case to trial.

The trials did reveal disturbing evidence of the researchers’ links to Big Pharma. Olson made about $240,000 from pharmaceutical companies during a six-year span, and about $149,000 of that came from AstraZeneca. Schulz made more than $500,000 from pharmaceutical companies and about $112,000 from AstraZeneca.

More than 10 years after the CAFE study, the legislative auditor of the state of Minnesota investigated deaths during clinical trials at the University of Minnesota.

The investigation report stated: “While we think it is impossible to make a causal connection between Markingson’s death and his participation in the drug study, we concluded that the case involves serious ethical issues and numerous conflicts of interest.”

Markingson’s case is just one personification of the obvious conflict of interest for-profit companies possess when funding studies to prove the safety and efficacy of their products. The suspected depth of corruption into academia – including university leadership, department chairs and individual researchers – is extremely alarming.

Clinical trials are the best scientific method for establishing the safety and efficacy of medical treatments. Researchers complete thousands of ethical, unbiased studies that advance medical knowledge and save lives every year. Big Pharma funds some of those trials. But the corruption of other studies taints the efforts of unbiased researchers seeking medical advancement.

When a for-profit, multi-billion dollar industry is in charge of products meant for public safety, someone is bound to get hurt.

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