Understanding clinical trials

By Aileen Tangonan MacAndrew and Noralyn Onto Dudt

Clinical trials are research studies with the goal of  testing  a medical, surgical, or behavioral intervention in people. These trials are the primary means  for researchers to determine if a new form of treatment  or prevention, such as a new drug, diet, or medical device  ( for example, a pacemaker) is safe and effective in people. The trials  study  new tests and treatments and then evaluates their effects on human health outcomes.

The importance of clinical trials in cancer care is evident in patients' overall survival.  Most patients with advanced malignancies are heavily pretreated with standard-of-care treatments. Thus, clinical trials in the practice of evidence-based medicine are important options for them. As clinical trials could  take as long as ten years, its application  involves dedication, patience, and great camaraderie among the entire research team: Primary Investigator, Sub-investigator, Research Coordinators/ nurses, Clinical Research Associates, and Clinical Staff. It's a well-orchestrated "dance" (a well-tuned coordination) that involves contractors whose staff can provide and analyze  laboratory  samples, and regulators who  make sure that every step of the trial is carefully observed.

Researchers conduct clinical trials in a series of steps called phases. Each phase has a different purpose and provides  clarification to an array of questions posed by  researchers.

Phase 1—test a medicine or other treatment on a small group of people for the first time. The purpose is to learn about the best dosage for a medicine or other treatment and to learn about the safety and side effects.

Phase 2—study the new medicine or treatment in a larger group of people to determine its effectiveness and to further study its safety.

Phase 3—give the new medicine or treatment to an even larger group of participants to confirm its effectiveness, monitor side effects, compare it with standard or similar treatments or a placebo, and collect information that will allow the new medicine or treatment to be used safely.

Phase 4—after the U.S. Food and Drug Administration (FDA) approves a medicine or treatment and it is made available to the public, researchers track its safety in the general population, seeking more information about the medicine or treatment benefits and optimal use.

For smoother coordination that would lead to better outcomes,  these phases must be explained not only to the volunteer patients but also to their significant others and caregivers.

There are many factors that affect how long it takes for a drug to be licensed. In fact some trials have taken 10 to 15 years to complete all three phases of the clinical trials before the licensing stage.

Who are qualified ? Each study has its own rules about who can—or cannot—participate.  This is called "eligibility." Your eligibility may be based on your age, gender, overall health, type and stage of a disease, treatment history, and other conditions. Not everyone is chosen to participate. The exclusion criteria state who cannot take part in the trial.  For example, people who are already taking particular medicines may be excluded as they may affect the trial treatment—factors such as comorbidities or  concomitant treatment  or factors that could also mask the effect of the intervention. To act in the best interest of the patient is a vital principle for the members of the research team. For patients to truly understand clinical trials, detailed discussion regarding the differences of study drugs versus standard-of-care therapies and outcomes are important. Patients must understand that participating in any trials is voluntary and they may withdraw from it as they wish. Patients are also informed that clinical trials are conducted in different health care facilities and institutes nationally and globally. The research team is trained to identify which patients are eligible and which patients are most likely to comply with the complexities and challenges that could turn burdensome (e.g. timing, transportation, insurance and other issues). The first step is to obtain consent and to explain to potential subjects that consents are a mandatory component of clinical history and confidentiality will always be maintained. After an informed consent is obtained, screening patients for clinical trials start. This entails lab draws, EKGs, CT scans, thorough assessments/evaluations of potential subjects per study protocols). In addition, discussions regarding side effects, potential adverse effects, risks, benefits, and symptom management are imperative.

Who manages  clinical trials? The Principal Investigator is the doctor who runs the study and is responsible for all study-related medical decisions. The Study Coordinator assists the principal Investigator and guides participants through the study experience.  Participants are the people who join clinical studies  and make research possible.

Clinical trials take place in doctor's offices, cancer centers,  medical centers, community hospitals and clinics, and veterans  and military hospitals. A single trial may take place in one or two places,  or at hundreds of different sites in university hospitals around the world where research scientists and medical doctors collaborate as was the case for the COVID-19 vaccines.

Before a clinical trial can officially begin, researchers must engage in two phases of laboratory research, known as the drug discovery phase. These phases allow for the discovery of new drugs and to test their potential effects on human cells or animal models.

A controlled study in clinical trial is an experiment that includes  a comparison (control group).

The controlled group does not receive the new treatment being studied. This group then is compared to the group that receives the new treatment, to see if the new treatment works.

An example of a control in science would be the cells that receive no treatment in an experiment. For example, a scientist testing how a new drug causes cells to grow. One group -- the experimental group -- would receive the drug while the other would receive a placebo. The group that received the placebo is the control group.

Control is critically important in the study to ensure that the observed results are not just random events: they help scientists distinguish between the "signal" and the background "noise" that are inherent in natural and living systems.

Safety and efficacy are other important components in clinical trials. Research physicians must evaluate, perform physical exams, assess, collect all information reported by patients, and educate patients. They are responsible in grading patients' adverse events of when actively taking study drugs, recognizing early signs of study drug- related toxicities to prevent patients from any deleterious effects, which can turn into hospitalization and, or death. Study drug adjustments and supportive care ( such as anti-nausea medications  or anti-inflammatories) are done according to study protocol if patients exhibit side effects.

SUNLIGHT (the clinical study mentioned in our previous article) was the first and only phase 3 study with an active control in third line metastatic colorectal cancer that demonstrated statistically significant efficacy. Phase 3 studies/tests the safety and how well a new treatment works compared with a standard treatment. For example, phase 3 clinical trials may compare which group of patients has better survival rates or fewer side effects. In most cases, treatments move into phase 3 clinical trials only after they meet the goals of phase 1 and phase 2.

According to the University of Maryland Medical School,  Clinical trials for COVID-19 vaccines have involved tens of thousands of volunteers of different ages, races and ethnicities. As the COVID epidemic was worldwide and the number of deaths was  increasing rapidly and exponentially, two government agencies—the Federal Drug Administration and the  Center for Disease Control—were heavily involved from the very beginning.

Many people were astonished at how quickly the COVID-19 vaccines were developed. Although the first vaccines were created, evaluated and authorized for emergency use in under a year, we can be assured that no steps were skipped in ensuring their safety and effectiveness. They went through the same layers of review and testing as other vaccines. Scientists have been working for many years, long before the start of the  COVID-19 pandemic,  to develop vaccines against coronaviruses. Knowledge gained through past research helped speed up development of the COVID-19 vaccines.

After their initial development in laboratories, all vaccines go through those three phases of clinical trials previously mentioned  to make sure they are safe and effective. The trials compare outcomes, including how many people get sick, between those who are vaccinated and those who are not. Then the U.S. Food and Drug Administration ( FDA) reviews the findings from the clinical trials before deciding whether to grant its authorization  or approval—a very thorough process that we can fully trust.

 

Aileen Tangonan MacAndrew, RN MSN  is a clinical nurse practitioner at the Hematology/Oncology University of California/ Los Angeles Health.

Noralyn Onto Dudt has written numerous articles on the Coronavirus and vaccines during the lock down days of COVID-19.