Madeline Eiken was a Hackworth Fellow for the 2018-2019 school year. She graduated from Santa Clara University in 2019 where she majored in bioengineering and minored in chemistry. She was awarded the Ethics Center Markkula Prize in June 2019. She currently works at Allosource, a tissue bank in Colorado.
Every drug and medical device must undergo a series of clinical trials in order to be sold to consumers. Clinical trials are an essential step of the research and development process for drug companies. Clinical trials consist of three stages, with an increasing number of patients enrolled in each consecutive phase. The trials are important to determine safety, efficacy, and dosage for the drug prior to making it available to patients. Clinical trials are one of the most expensive steps in pharmaceutical and device development for biomedical companies. Each phase of the trial can cost up to twenty million dollars to run.
Running clinical trials in the United States has difficulties beyond its high cost. It can be challenging to enroll an adequate number of patients into each trial, and the dropout rate can be high, further increasing the cost and time associated with running a clinical trial. Due to these factors, some big drug companies prefer to perform their trials in low or middle income countries, like Russia, China, or India, where it is much cheaper, enrollment rates tend to be higher, and dropout rates tend to be lower. For example, the cost of running a clinical trial in China is one-third of the cost of running a clinical trial in the U.S.
Today, 40 percent of all clinical trials are performed in developing countries, up from 10 percent in the 1990s. Proponents of international trials claim that the relevant ethical standards are equivalent everywhere in the world and that the reduced cost of the trial makes performing trials offshore highly attractive to U.S.-based companies. Additionally, performing studies in several countries around the world can help to ensure that there is a diverse patient population testing the drug. People in low or middle income countries tend to take fewer medications than people in high-income countries, reducing the potential effects of drug-drug interactions.
Despite the claim that universal ethics standards are followed, one of the major ethical considerations in all clinical trials is the concept of informed consent, especially when working offshore. Getting informed consent is absolutely critical for an ethical clinical trial, especially because participants in a clinical trial are exposed to a significant amount of risk often without associated personal benefit. There are several standards that must be met in order to ensure that trial participant informed consent has been achieved. In the case of testing a new potential treatment, patients must have full knowledge of their diagnosis and treatment options. Furthermore, they must understand the potential risks and benefits associated with enrolling in a particular clinical trial and with their other options, including standard treatments or doing nothing. The decision to enroll in a trial cannot be coerced, and must be made with full mental capacity and understanding of risks and benefits.
Which patient populations may not be able to give informed consent? Should these populations be excluded from clinical trials? Why or why not?
Consider this: an American pharmaceutical company we’ll call Rx has chosen to do clinical trials in Russia. They are testing a drug for arthritis that they hope will have fewer side effects than currently available medication. The cost for this offshore trial is much cheaper and there is a much higher rate of enrollment than there would be in the U.S. When Rx investigates the high enrollment rate, it turns out that the majority of patients enrolled in the trial do not have access to medical care, and the trial represents a way for them to get care for a few years for free.
Is the promise of free medical care for participation in a trial inherently coercive? To decrease the potential for unintended coercion, should trials be limited to patients who have ready access to medical care?
Rx also finds that the majority of the patients enrolled in the trial do not have a relevant educational background. Few of the patients have an eighth grade education, and they are not familiar with basic scientific concepts like cells or bacteria. Rx believes that participants have been properly consented because they were given a detailed consent form and they signed it. The consent form outlined the potential risks and benefits associated with the trial and described the mechanism by which the drug works and the duration of the trial. They were also able to ask the researchers running the trial any questions that they had.
What is necessary for a patient to know going into this or any clinical trial? Can we consider it truly “informed” consent if the patient does not understand the science? Do participants need to understand how a drug works in order to consent to taking the drug? What responsibilities do physicians have to ensure that their patients are well-informed?
The final stage of the trial ends successfully after four years in Russia; the new pharmaceutical works. The Rx team returns home. Trial participants stop being provided with the drug for free and lose their access to the medical care that they had enjoyed during the trial. They are not allowed to contact the doctors who took care of them now that the trial is over. The outcomes of the trial are good, and the FDA approves the drug in the U.S. Rx will make the most money by selling to the U.S. market and plans primarily to focus on U.S. advertising and distribution. Given the pricing structure, this new arthritis treatment will likely be too expensive for clinical trial participants to continue their treatment potentially reversing the good progress they had made in combating the pain, joint damage, and disfigurement caused by arthritis.
What, if anything, is owed to the participants of the trial? Is it fair for Rx to cease to provide this successful treatment to those who helped them get it approved for sale?