Clinical trials have a bias problem.

Most participants of clinical trials–which lay the foundation for drugs approvals–skew heavily white and male. It’s an important concern: clinical trials help formalize the safety and efficacy of a drug, along with its dosage. In plain terms, they lay the groundwork for physicians prescribing a pill to their patients. But if racially and ethnically diverse populations aren’t included in these studies, we can’t know whether the same treatment, at the same dosage, will work in all populations. We also won’t know if some side effects emerge in one group or another.

Take a dosing example: if the drug dosage is tested using males, who on average tend to have a higher body weight than females, the same dosage could be too much for women resulting in over-medication.

It’s an unresolved problem when it comes to epilepsy. In addition to differences in average body weight, women and men have different hormone levels that could influence seizure control. When it comes to complications of anti-seizure medication interacting with additional drugs, such as hormonal birth control, the problem gets more difficult.

Part of the reason drug efficacy and side effects have been difficult to suss out for different gender and ethical groups is that clinical trials are expensive to run, and often are able to only recruit a certain amount of people. However, once the drug is approved, feedback from patients in far larger numbers then become a precious resource to further fine-tune prescriptions–both in terms of the type of drug and its dosage.

A key point is for a sufficient number of people to report their medication adherence and side effects. With sufficient case studies, these real-world data, or “real-world evidence,” can further guide doctors to prescribe medication tailored to their patient.

What are clinical trials?

In short, a clinical trial is a multi-stage process to ensure a new drug is both safe and efficient at a particular dose or a handful of different doses. Normally, these trials come in three phases:

• Phase 0 (not often): People are given a drug candidate to see how it’s processed in the body, and affects the body. These trials are very small, with usually about 10 to 15 people.
• Phase 1: This stage tries to identify the best dosage of a drug candidate that is safe. Generally, healthy volunteers test the drug candidate in increasing dosage. As the drug’s dosage increases, side effects also often become more profound. This stage identifies drug candidates that are effective at a dose that doesn’t have intolerable side effects.
• Phase 2: This stage asks if a drug works. The drug is tested in a small number of people with epilepsy. Sometimes new combinations of drugs are tested. Here, participants are closely monitored to see if a drug works, compared to a placebo–often a sugar pill–or the current standard-of-care drug. If the drug candidate works to help control seizures, it is then moved onto the next phase.
• Phase 3: the big one. This drug trial enrolls more patients, and often are randomized. This means that any patient could receive either the treatment or a control group by chance. Single-blinded trials mean that the patient doesn’t know if he or she is receiving the treatment or placebo. Double-blinded means that neither doctor nor patient knows who’s getting what treatment. This makes it more objective to judge if a drug is working or not, because it roots out expectations and bias.

What happens after clinical trials?

When you take a drug, it goes to the liver where it is “metabolized”–that is, some are broken down–and both the broken-down bits and the whole medication may go into the brain. Different livers have different abilities to break down a given medication. This is often seen in how men and women can process the same drug slightly differently. This variability is normal to all of us, and illustrates how we are all unique.

However, it does pose a problem to how much of a medication you should take. Because of biological differences, a drug and dosage that’s been clinically tested in men may be too much for women, or have unexpected side effects. Similarly, a drug may also interact differently with genetic backgrounds. When it comes to seizures, which are highly variable and individualized to begin with, optimizing medication to for any given person–or “personalized treatment”– becomes more complicated.

This is where after-market reports can help. If everyone who is taking a medication to control their seizure can report how well the drug works and what the side effects are, we can begin to build a database to better understand how anti-seizure medication works for different sorts of people. For example, scientists may be able to tease out a better dosage to prescribe to a gender, an age bracket, or someone with epilepsy and other conditions or comorbidities. Data from actual people with epilepsy in the real world, or “real-life evidence,” form the foundation of stratifying and personalizing medicine.

But to get there, we need to be able to capture those data without bringing extra stress into the lives of people with epilepsy or their caregivers. With nEureka® for Epilepsy, patients can easily log their basic physiology, medication and side effects. When given consent, the data is then anonymized into a central database in the cloud. These datasets are critical for epileptologists and scientists to mine for further insights.

With nEureka®, we hope to one day solve the gender and racial bias issue in clinical trials–instead bringing personalized treatment to you, no matter who you are.

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