The Food and Drug Administration (FDA) approves over 20,000 drugs for public use every year in the US. But do you ever wonder how researchers, doctors, and government agencies develop and test these drugs before they reach the market? It's a lengthy and meticulous process that takes 10–15 years and involves clinical trials.
Clinical trials test how health interventions (drugs, vaccines, medical devices, surgical techniques, and changes in behavior to improve health and quality of life) impact our health before making them available to the public. Through rigorous testing, clinical trials help researchers determine whether these interventions effectively treat specific diseases or conditions. They also provide important insights into potential side effects, optimal dosages, and the appropriate patient population for a particular treatment.
Without well-designed trials and the involvement of government agencies in these trials, we lack sufficient evidence to determine the effectiveness and safety of a treatment and run the risk of giving ineffective or potentially harmful treatments to individuals.
Learning about clinical trials is essential. It empowers individuals to make informed decisions about their healthcare, access innovative treatments, advocate for patient-centered research, understand healthcare information, and appreciate the ethical considerations in research. By understanding clinical trials, individuals can actively participate in their own care, engage in discussions that shape healthcare advancements, and promote equitable access to cutting-edge treatments. It enables the public to navigate the complex landscape of medical research, ensuring they receive the best possible care and contributing to the improvement of healthcare outcomes for themselves. In this article, I provide an overview of the process, challenges, and ongoing innovations in clinical trials.
How are modern clinical trials conducted?
Modern clinical trials involve several stages. They start with laboratory research, where scientists develop these promising health interventions before moving on to human trials.
Government agencies, like the FDA, monitor each stage of the process to ensure ethical conduct and adherence to guidelines. Institutional Review Boards (IRBs) also play a crucial role in safeguarding participant rights and safety.
Before conducting human trials, researchers submit an Investigational New Drug (IND) application to the FDA to ensure participant safety. Approval from the FDA and the Center for Drug Evaluation and Research (CDER) is required both to begin and end the trial.
Clinical trials typically progress through different phases. Phase 1 involves a small group (20–80) of healthy volunteers assessing the treatment's safety and side effects. Phase 2 expands the study to a larger group of patients (100–300) to evaluate effectiveness and safety. Phase 3 compares the new treatment to existing standards or placebos in a larger patient population (1000–3000) to assess its performance. Phase 4 involves post-approval surveillance studies to monitor long-term effects and refine treatment guidelines.
Clinical trials include various types, like prevention trials (aimed at disease prevention), screening trials (testing new detection methods), diagnostic trials (studying or comparing diagnostic procedures), treatment trials (testing new treatments or approaches), behavioral trials (evaluating behavioral changes for health improvement), and quality of life trials (exploring ways to enhance comfort and well-being).
Several new types of clinical trials have emerged in recent years to address specific research needs and adapt to evolving medical landscapes. Here are two examples:
Adaptive Clinical Trials: A clinical trial protocol is like a roadmap or a set of instructions that guides researchers, doctors, and other members of the trial team on how to conduct a clinical trial. In a typical clinical trial, researchers cannot change clinical trial protocols during the trial. However, during an adaptive trial, they can improve the trial protocol while it is ongoing.
These trials allow researchers to make real-time adjustments to the trial protocol or design for better outcomes. Due to their flexibility, adaptive trials can save time and resources, allowing researchers to assign more participants to treatment groups showing the most promise.
Master protocols: Master protocols stand out from typical clinical trials because they explore multiple questions or ideas within a single trial. These features make master trials practical for evaluating multiple treatments or interventions within a single trial structure.
Challenges of current clinical trials
90% of drugs fail clinical trials. A well-known example of a failed clinical trial was for the drug thalidomide, initially created in Germany for treating respiratory infections, which gained notoriety due to its devastating impact on pregnancy. Thousands of children born in the 1960s suffered severe impairments, including limb abnormalities and cleft palates, resulting from this drug. Researchers overlooked the drug's effects on offspring during the clinical trial phase, leading to its approval in 1956. In 1961, the Australian doctor William McBride discovered the connection between thalidomide and deformities.
Some examples of challenges faced by clinical trials that can impact their progress and outcomes are:
Costs: The cost of clinical trials can vary a lot, depending on different factors. Things like how many patients they need, how many research sites are involved, how complicated the trial is, and how much investigators are reimbursed can all affect the cost. In fact, for a big trial that involves multiple centers, the total cost can go up to $300–$600 million! That's a lot of money needed to make sure the trial is carried out, monitored, and completed successfully. One way to reduce these costs is to simplify clinical trials.
Recruitment and Retention: One of the primary challenges is recruiting enough participants who meet the specific criteria for the trial. Low recruitment rates can make the study take longer to complete, make the conclusions less reliable, and make it harder to apply the findings to a larger group of people. Retention of participants throughout the trial duration is equally essential, as dropouts can compromise the integrity of the data.
Diversity and Representation: Clinical trials often struggle with achieving diversity in participant demographics, including age, gender, ethnicity, and socioeconomic status. This lack of representation can make it harder to apply the findings to larger populations and limit our understanding of how different groups of people respond to treatments.
Clinical trials hold promise for medical progress. For instance, ongoing trials are exploring the development of a universal flu vaccine that can protect against a wide range of flu strains, addressing the limitations of current vaccines. The future holds promising innovations in the clinical trial process, leading to the faster development of more effective treatments for better human health.
