Are Clinical Trials Safe?

Clinical trials have been an important method for testing potential treatments for a long time. If you have a disease with no known cure, or conventional treatments don’t work for you, perhaps you’ve considered, or tried, a clinical trial. But are clinical trials safe? Does the US government protect us against harm from clinical trials? Should we consider a trial for ourselves or a loved one? 

The first clinical trial in medicine.

Clinical trials have a long history – longer than most realize.

In the early 1700s, a few doctors thought that citrus fruits might cure scurvy, a common scourge for sailors, but not all doctors agreed. So in 1747, Dr. James Lind decided to methodically test the theory, leading the first controlled clinical trial in medicine.

He divided a group of 12 sailors with scurvy into 6 groups of 2 men each. After only 6 days, the 2 men who ate citrus fruits showed miraculous improvements. Unfortunately for Lind and for sailors at the time, it took almost 50 years before others recognized the merits of his discovery.

How many clinical trials are run each year?

The number of clinical trials has skyrocketed in recent years. In fact, the annual number of registered clinical trials registered with The International Clinical Trials Registry Platform increased from 3,294 in 2004 to 23,384 in 2013.

Furthermore, ClinicalTrials.gov currently lists a total of 353,722 studies with locations in all 50 States and in 216 countries. According to the site, on October 5, 2020, there were 18,260 clinical trials in the US actively recruiting participants.

What kinds of things do researchers study?

Clinical trials aim to determine if a treatment is safe and effective. Although many of us think of testing medications when we think about clinical trials, in actuality there are 4 main categories of treatments (also called interventions) studied in clinical trials:

• Drug or biologic
• Behavioral
• Surgical procedure
• Medical device

What are the benefits of clinical trials?

Without clinical trials, it would be impossible for scientists to know if a potential treatment is safe and effective. These trials are a critical part of medicine. We all benefit from the knowledge learned during trials.

For patients who participate, clinical trials provide access to a new treatment before it’s available to other patients, as well as other benefits.

It’s not overstated to say that clinical trials can literally save a patient’s life when all other treatments have failed. But clinical trials can pose dangers to participants as well since not all clinical trials are safe.

How do researchers keep clinical trial participants safe?

Federal laws require all clinical researchers to follow strict rules with a plan to keep every participant safe.

To make sure researchers embark on safe, well-designed studies, an IRB (Institutional Review Board) at each study site must approve proposed studies. After the IRB approves a trial, the team of doctors, scientists and lay people regularly review each study and its results.

Additionally, many sites have a Data and Safety Monitoring Board that closely supervises trials. These independent groups of experts look at the results as the study progresses. If they find that a treatment is not working, or is causing harm, they can stop the trial immediately.

And, on top of these safety precautions taken at each trial site, the FDA has the authority to enforce the law. In the past few years, the FDA disqualified some researchers for falsifying data and for other noncompliance issues. Some of the violations were so egregious, the researchers are in jail.

And, the FDA has halted trial enrollment until the IRBs fix procedural issues. However, 3rd-party investigations into FDA oversight discovered a sometimes-lax approach by the FDA when it comes to enforcing the law. (Read more on the FDA’s lax oversight below.)

Potential clinical trial safety issues.

Importantly, every treatment, even the older reliable ones, carry a degree of risk.

But, because clinical trials generally involve untested treatments, participants may suffer from side effects, ranging from mild to serious. Examples of possible side effects include pain, rashes, numbness, fatigue, pneumonia, colitis, diarrhea, and hepatitis.

In the worst-case scenarios, patients die. For example, the deaths of 44 patients were associated with experimental treatments received during clinical trials for breast cancer. Another study found that hundreds of cancer patients died from side effects related to clinical trials evaluating immunotherapy.

On the other hand, a trial’s treatment might not work at all, or may be no better than the standard, existing treatment. In most trials, a group of patients receive the experimental treatment, while others receive either a standard or a placebo (fake) treatment.

In some cases, a patient’s conditions may not improve, or may even worsen as time passes without an effective treatment.

For more information on trial safety, visit the Clara website.

Does the FDA ensure clinical trials are safe for patients?

The Food and Drug Administration oversees most clinical research in the US as well as overseeing some research conducted elsewhere for the US market. They are responsible for making sure clinical trials don’t harm patients and provide quality, trustworthy data. Currently, the FDA has 102 inspectors who:

• Respond to whistleblower complaints of dangerous operations.
• Conduct routine visits to trial sites.
• Review records of trial sites.

Although the FDA can require a violator to clean up serious transgressions and can even disqualify a scientist from clinical research, they often fail in their oversight.

Science investigates FDA inspection results.

The results of an investigation conducted by Science revealed a disturbing lack of oversight by the FDA. Data from the past 11 years (2009 – 2019) found the FDA’s oversight was often light-handed, slow-moving, and secretive.

The investigation found that it was unusual for inspectors to demand corrections when they found dangerous or unlawful clinical trial practices, even when finding signs of patient harm and/or corrupted data.

Furthermore, in the rare cases where the FDA notified researchers about evidence showing the researchers broke the law, the FDA often neglected to make sure the researchers fixed the problems. Finally, Science found that the FDA frequently closed cases based on unverified claims by the accused researchers.

Oversight is getting worse.

According to the Science investigation, the lack of FDA oversight appears to be worsening. For instance, the FDA issued 99 “warning letters” for serious transgressions during Obama’s first 3 years in office, yet they issued only 36 in Obama’s last 3 years.

Moreover, they issued just 12 warnings during the first 3 years of Trump’s term. This reduction in enforcement clearly puts participating patients at risk and raises questions about the validity of the reported findings.

An example of FDA failing to stop unsafe clinical trials.

Over a 10 year period, the FDA repeatedly cited osteopath Michael Harris, the Chief Medical Officer at Aspen Clinical Research, for egregious errors in clinical trials he oversaw. During this time, FDA inspectors discovered a wide range of problems at the company.

For example, the inspectors found:

• Serious lapses in the informed consent process for trial volunteers.
• Medical assessments made by unqualified staff.
• Failure to properly report abnormal lab test results.
• Failure to disclose that trial participants were taking opioid, antidepressant, or antipsychotic drugs – which could skew results and/or pose safety concerns.

Furthermore, the FDA said Aspen’s “records were disorganized, contradictory, and sometimes backdated in a way that begs the question of the authenticity and veracity of data collected.”

Additionally, Science obtained FDA documents that stated Aspen had “serious, ongoing deviations” which might constitute “fraud, scientific misconduct” and posed “significant human subject protection violations”.

In response to these findings, FDA inspectors repeatedly told Harris he could face fines, permanent disqualification from clinical research in the US, as well as legal prosecution.

However, the problems at Aspen continued, including new issues found during inspections in 2014, 2015, and 2019. Each time the FDA identified misconduct, Harris admitted some transgressions, strenuously disputed others, and promised to improve.

Despite these repeated, serious offenses, the FDA never formally sanctioned Harris or pursued other penalties. Nor did the FDA notify the public or tell trial participants they may have been in danger.

Moreover, the FDA never told the companies sponsoring these trials their data may be erroneous.

Perhaps most disturbing, Aspen continues to conduct clinical trials today.

My son Zach’s clinical trial journey.

When Zach was diagnosed with a diffuse intrinsic pontine glioma (a terminal pediatric brain tumor), no effective treatment existed. He immediately began a course of radiation and entered a clinical trial for a chemotherapy medication used for lung cancer.

The radiation and medication kept the tumor at bay for 1.5 years. Although the side effects of the medication increased each month, Zach was able to function like a normal teenager. We were thrilled this clinical trial extended his life beyond the 4-6 week survival prognosis given at his diagnosis.

However, the first medication stopped working and he was quickly removed from the trial. After several anxious months with no treatment, he enrolled in a new chemotherapy trial.

Although the new chemotherapy led to minor improvements, it also caused brain swelling, a deadly side effect. To combat the swelling, Zach’s doctor put him on a high dose of a steroid, which controlled the swelling.

But the steroid led to a fatty tissue deposit in his spine, which soon caused Zach to struggle with walking and standing.

A third clinical trial to treat side effects from the second trial.

We were desperate to get him off the steroid, so we felt lucky to get him into a clinical trial for an alternative medication for brain swelling. We knew that Zach would either receive the new medication or a higher dose of the steroid.

Feeling like we had no choice, we hoped for the best. Tragically, it soon became evident that Zach received the additional steroid. As each week passed, he lost more and more mobility.

We pulled him off the trial, but the damage was done. Now completely paralyzed from the steroid, he developed a deep vein thrombosis which ultimately led to his death from respiratory failure.

Looking back on the decisions we made to enroll him in 3 clinical trials, we know we did what we thought best at the time, with the information we had, in an attempt to extend his life.

The chemotherapy trials kept him alive for over 2 years – each of those days a cherished gift that would not have been possible without the clinical trials. However, the steroid trial hastened his death.

Still, we feel fortunate that we had the opportunity to enroll Zach in these trials.

Considering a trial?

Before signing the informed consent, make sure you know all the details of the study, including potential risks and side effects. Importantly, realize the signed consent does not obligate you to continue participating. You can leave a trial at any time, for any reason.

Additionally, I suggest you consider the American Cancer Society’s list of questions to ask yourself before choosing to enroll in a clinical trial:

• Why do I want to take part in a clinical trial?
• What are my goals and what do I expect if I decide to take part? How realistic are these?
• Have I looked at my other options?
• How sure are my doctors about my future if I decide to take part (or not take part) in this clinical trial?
• Do I have all the information I need to make an informed decision?
• Have I weighed the benefits against the risks?
• Have I thought about other factors, such as travel, time, and money?

Finally, a patient’s condition and prognosis are important when deciding if a clinical trial is the right choice.

If you, or a loved one, have life-threatening cancer that isn’t responding to available treatments, enrolling in a clinical trial can be an easy choice. But, if you’re thinking about enrolling in a clinical trial for a non-life-threatening condition, such as for pain or migraines, weigh all of your options carefully before deciding.

To learn more, read: What You Need to Know About Clinical Trials Before You Sign the Dotted Line.