Imagine you are writing a recipe — it would be important to make sure that your recipe includes all the necessary information so that any cook could follow your instructions and get the same result as you every single time. If that level of reproducibility is important when an author is writing a cookbook, then elements such as a tightly controlled environment and accurate measurements are even more critical in designing a scientific or clinical research study.
When I worked in the lab, I wanted to be sure that I had done my experiment enough times under very controlled conditions to ensure that I could predict what would happen. I would figure out how many times I needed to repeat an experiment to make sure that my studies had the statistical power to answer the question I asked, but I would frequently repeat an experiment more times than required to have a more robust data set. More was always better. Of course, there was some extra cost to expand an experiment, but the cells in the dish didn’t mind if we captured data at a few extra timepoints, and graduate students don’t really need to graduate on any sort of timeline. Or sleep, for that matter. In graduate school, all we really had to consider when planning a study was the pure science of it and whether we could get it published, hopefully in a top-tier journal.
When your research depends not on cells in a dish, but on living, breathing people, there should be a few more considerations in study design. Thankfully, institutional review boards, which must approve all clinical research studies involving humans, evaluate proposals to ensure patients are protected and the procedures are ethical. Truly patient-centered research, however, goes far beyond just ethical considerations to also consider the patient’s experience as part of the study and how participating in the research study impacts the participant’s daily life.
Clinical Research Design — Science Matters
As a patient, it seems obvious that the design of any clinical research involving patients should be heavily influenced by patients and their experiences. But remember, it’s scientists who are designing these trials. Their goal is to get data — lots of high-quality data — in their quest to predict how future patients will respond to the same treatment. When scientists design an experiment, they need lots of timepoints — multiple biopsies, blood draws, and doctor visits, and they need patients to fill out extensive surveys. Scientists are trained to set up a protocol (science’s version of a “recipe”) that is tightly controlled to maintain the integrity and value of their data, knowing that bad data won’t help anyone. Ideally, all the lab work would be done in one lab, everyone would receive scans on the same machine with the same doctor reading the results, and all the patients would see the same lead physician in person on a regular basis. That’s an ideal scenario, but the patients we are talking about are far more than just study participants. They are fathers, mothers, teachers, musicians, coaches…and their time is precious.
Clinical Research Design — The Patient Matters
To ensure that a trial is truly patient-centric, it’s important to involve patients in the design process. Patients will challenge the investigators!
- Patients will ask investigators whether the extra effort that comes along with participating in a research study is necessary.
- Have you simplified the informed consent documents and included a patient-friendly summary so that patients can better understand what they’re reading?
- Do you really need that many biopsies, blood draws, or long surveys?
- Is it necessary for the patient to be seen in the clinic that frequently?
Perhaps some of the repeat visits aren’t completely necessary. Maybe three blood draws will suffice instead of six, and the protocol can be adjusted. But some of that extra work is critical to getting enough data to allow investigators to draw conclusions and can’t be eliminated. And, knowing how to explain that to patients is also important.
- Patients will ask whether the investigators have made accommodations for the extra effort that is necessary.
- Do all the blood draws have to be done at the primary study site, or can they be done at a lab closer to the patient’s home?
- Can scans, blood draws, and doctor visits be scheduled on the same day to reduce travel time?
- Can surveys be done online or through an app to gather real-time data in a way that seamlessly integrates with the patient’s lifestyle?
- Have you made sure that your surveys ask the most important questions, but not lots of extra questions?
- Is there a patient navigator to help the patient find resources like rides, childcare, or emotional support?
- Patients will ask questions about exclusion and inclusion criteria.
- Have you been thoughtful about who is excluded from your trial, or did you just copy and paste a historical boilerplate list? (With the FDA and the American Society of Clinical Oncologists recently calling on investigators to modernize eligibility criteria, clearly patients aren’t the only ones asking these questions.)
- Have you been thoughtful about your drug-washout periods? Many studies require a patient to be “drug free” for between 30 and 90 days. Some drugs have a very long half-life — they stay in a patient’s system for a long time, so the washout period makes sense. But many do not. Having a 90-day washout period for a drug that’s not in a patient’s system after a week leaves a patient untreated for an unacceptably long time.
Everyone Benefits from Patient-Centered Research
It’s obvious how a patient-centered clinical research study helps patients — it makes things easier for them. But it’s admittedly less obvious how this helps the investigators. It makes things harder for them — they have to be more thoughtful, and they might not get as many data points. Including more patients in the research may mean that they are incorporating more people who have other health issues that might make the data harder to interpret. But adding patient-centered ideals will not only increase the value of the scientific data that are produced, but they can encourage more widespread use of the treatment as well — huge benefits that no investigator should overlook.
- Quicker recruitment. Fewer barriers to participation in a clinical research study means investigators can find more participants more quickly. Speeding up the regulatory process means that effective drugs will be available to all patients sooner.
- Higher retention. A lot of people initially commit to be part of a study only to find the procedures too onerous, and they ultimately withdraw. Again, the quicker a study can be completed, the better. In addition, if participants withdraw from a study after the recruitment phase is over, they can’t be replaced by enrolling additional patients. In the best case, the study loses some of its statistical power. In the worst case, the study can’t be completed because the sample size is too small. Making sure patients understand the study and aren’t overburdened prevents the dropout that can cripple a study.
- Expanded label. Once a drug is approved by the FDA to treat a particular condition in a particular patient population, that information goes on its label. Most insurance companies will cover its use in those situations. Medical doctors, however, are free to prescribe it to any patients they think would benefit, and this includes many “off-label” conditions or patients. Most insurance companies aren’t eager to cover off-label use, and that lowers drug utilization. More diverse patient populations in a study can result in an expanded label for the treatment, which means that patients from all communities can have confidence that a drug is safe and effective for them, and that the medication they need is more likely to be covered by their insurance.
All of the stakeholders involved in the clinical research process share a common goal: to get safe and effective drugs to patients as quickly as possible. Thoughtful, patient-centered design of clinical research studies can accelerate the realization of that goal.