Clinical trials are the studies that determine if a drug (or medical device or any kind of treatment strategy) is effective and safe. These are the two main reasons to do a clinical trial. Before a medication can be approved for general use it has to be determined that it does what it is supposed to do and that it is safe to use.
Although they can take years to complete, clinical trials are actually the end point of the path a medication takes from discovery to market. Before any drug can be investigated in a clinical trial, it has to be shown to have promise in laboratory and animal studies. Whether a new drug is found in clinical trials to be safe and effective, harmful, or to have no effect, the information is useful to research.
Drug companies play an important role in clinical trials. A trial for a new drug is typically sponsored by the company that created it, but the process is overseen by the Food and Drug Administration (FDA). These trials are expensive, and most often do not lead to a drug that can go to market. Because pharmaceutical companies are driven by profit and shareholders, the influence they have over trials and reported results of those trials is controversial.
Clinical Trials and Funding
Funding, or sponsorship, for clinical trials depends on what is being tested. The National Institutes of Health sponsors many trials that investigate treatment strategies. Examples include investigating the benefits and risks of lowering blood pressure in elderly patients or determining the best age at which to start screening women for breast cancer.
Clinical trials may also be sponsored by other government agencies, by academic institutions like universities, by nonprofit groups, and by private companies. The latter is where drug companies come in. The pay for and sponsor most clinical trials for the drugs they create and hope to bring to market. While in the past, companies would hire research groups to design and run their clinical trials, today it is more common for a pharmaceutical company to run the show. They still may hire researchers, most often from teaching hospitals and medical schools, but they more often dictate how the trial will be designed and how it will run.
In fact, in many cases the sponsoring company takes the collected data, keeps it, and writes up the paper or report on the results. The academic researchers may not even be given access to the data from the trials they are conducting. This is contrary to standard scientific research principles and hinders good research. The academic researchers may even have monetary ties to sponsoring pharmaceutical companies, some serving as paid consultants.
This funding connection and the way that clinical trials are run for drug companies raises eyebrows as it clearly illustrates a conflict of interest. The company sponsoring and running the clinical trial has a lot invested in the experimental drug. They want it to succeed, and that can lead to unethical practices as well as real and dangerous consequences for patients.
Clinical Trial Results Are Not Always Published
Scientific research builds upon the work of previous studies. Even when a study is considered to have failed, such as a drug that was not effective or was not safe, the results are important for informing further research. Unfortunately, pharmaceutical companies don’t always publish results of clinical trials when they are negative because they need positive results for profits. This practice harms patients.
To combat the potential harm to patients when negative results aren’t published, the government set a requirement that all clinical trial results relating to life-threatening and other serious illnesses are reported on a government website. Not all drug companies stick to this rule, though, and results continue to go unpublished.
Unpublished negative results from clinical trials can harm patients because sometimes those results show that a medication causes dangerous side effects. In other cases, the results may show that a drug doesn’t work. FDA approval only requires that one or two trials for a drug prove its effectiveness, even if other trials showed it to be ineffective.
The tendency to publish only positive results in research I called publication bias, and there are few examples of how dangerous this can be for patients than the case of Lorcainide. A clinical trial for this drug, developed to treat heart arrhythmia, showed that it may be harmful. In the 1980 trial, nine patients taking the drug died. Those results were not published until 1993 after more than a decade of doctors unknowingly prescribing this dangerous drug to patients. Thousands of patient deaths can be blamed on this particular case of publication bias.
Pharmaceutical Companies Play Cover Up
Publication bias is often intentional, even if those who fail to publish don’t fully realize the negative impact it could have. An even worse example of what drug companies may do to promote profits is cover up negative results. These results may harm the bottom line, and so they bury them and too often patients suffer the consequences.
Such was the case with Tamiflu, a drug designed to reduce the duration and severity of influenza. What happened with Tamiflu demonstrates how important negative results are, how important it is that the information is available, and how tragic the consequences can be when a drug company tries to hide this kind of information.
Many people have used Tamiflu and have had no serious negative side effects. However, since it came on the market, at least 70 people have died using Tamiflu. In many of these cases, the drug induced a psychotic state, hallucinations, and led people to commit suicide. Although the odds of having that reaction are rare, it is possible and the consequences are tragic.
An investigation by an independent organization looked into Roche, the company that developed Tamiflu, and found troubling evidence of a cover up. Roche sponsored several clinical trials. Some of the results were submitted to the FDA and the drug was approved in 1999. Many of the results, though, including 100,000 pages, were intentionally left out of the report sent to the FDA. These included trials with inconclusive results and evidence that Tamiflu is not very effective.
Roche continues to deny they had any evidence the drug might cause psychotic episodes and suicidal thoughts in patients. However, the fact that 70 or more people have experienced such episodes and the number of trials they conducted makes it seem unlikely that this is true. The company admits that they saw the psychosis in some patients in the trials, but denied that it could have been linked to Tamiflu.
When Clinical Trials Go Wrong
A drug cannot make it to the clinical trial stage until it has been proven safe in animal studies. This does not guarantee that there won’t be issues in humans, but it does rule out potentially dangerous substances and lowers the risk for patients in clinical trials. To further protect patients, the first phase of a trial is small, with just 20 to 50 patients.
There is still always a risk that a patient in a trial will experience negative side effects from a study drug. Both the company sponsoring the trial and the researchers conducting it are responsible for taking care of trial patients and ensuring that the study is conducted as safely as possible. When they don’t take that responsibility seriously, or purposely do things that are unethical, patients can suffer and even die.
An example of such a situation occurred during an AstraZeneca trial conducted at the University of Minnesota. A young man involved in the trial was suffering from bipolar disorder, schizophrenia, and psychosis. He committed suicide and died while taking the trial medication. A doctor involved in the study initially treated the man, Dan Markingson, and declared him unfit to make decisions about his own care. He soon after retracted that and enrolled Markingson in a clinical trial.
Markingson’s mother protested his participation and repeatedly tried to get him out of it. The drug being tested in the trial had so far been found to be ineffective. Reports later showed that Markingson’s condition deteriorated throughout the trial, but the head trial researcher, the doctor who enrolled him, refused to take him out of the study.
After Markingson died, the Institutional Review Board of the University failed to investigate and filed complaints were ignored. Markingson’s mother has tried again and again to get justice, but cover ups have prevented her from doing so. Lawsuits, malpractice suits, and other efforts have been denied.
Evidence shows that there was good reason to investigate. The doctor who enrolled Markingson received money from AstraZeneca to complete the trial. One investigation conducted ten years later concluded that there were serious ethical violations, even if it could not be proven that the trial directly led to the death of the patient.
Clinical trials are important for getting new medications to market, drugs that treat people effectively and save lives. On the other hand, these trials and the way they are conducted leave a lot of room for serious and unethical practices, conflicts of interest, publication bias, and cover ups, all of which have huge potential to hurt people.