Are Clinical Trials Safe?

Clinical trials are crucial for advancing medical science and finding new drugs and treatments that can treat and cure various conditions and diseases. Clinical studies can also make it possible to diagnose conditions earlier so treatment can be administered quickly - providing valuable insights that can only be discovered in a real-world environment.

However, many people have misconceptions about clinical trials regarding their safety, including the potential adverse effects caused by experimental treatments or a lack of effectiveness. Anyone participating in a clinical trial should be fully informed of what the study will entail and the possible risks and benefits of the clinical trial treatment when compared to standard treatments.

In this article, we discuss what makes clinical trials safe, from ongoing monitoring to the regulations set out by review boards that all studies must adhere to. We will also discuss why clinical trials are important, common concerns, technological advancements in trial safety, and much more.

Common concerns about clinical trials

Many people who may be eligible to participate in a clinical trial are reluctant to do so because they have concerns about the possible outcome.

Like all medical treatments, those provided in a clinical trial may present risks in terms of side effects or a lack of efficacy. Meanwhile, other concerns could include being given a placebo instead of an active treatment, or perhaps the feeling of being used as a guinea pig for an experimental medical intervention.

Here are some of the common concerns people have about participating in clinical trials and studies.

Will there be risks?

Like any form of medical test or treatment, a clinical trial does present an element of risk. However, many people participating in a clinical trial feel the potential benefits of an experimental treatment can far outweigh the risks, while some people may feel differently.

Will I be a “guinea pig?”

You will not be a guinea pig by participating in a clinical trial. Even though this type of study is designed to answer medical questions. Clinical trials go through many phases to determine the safety of the treatment to reduce the likelihood of unintended results.

Furthermore, many people welcome the additional care and attention they receive during a clinical trial compared to standard healthcare treatment.

Will I get a placebo?

Some clinical trials do use a placebo to gain wider insights into the effects of a treatment, but this is only sometimes the case. A placebo would not be used in a clinical trial if it could put a person at risk by not providing them access to an effective treatment.

Have concerns about joining a clinical trial? Get peace of mind by asking the right questions. Explore our detailed guide on what to ask before participating and feel confident in your decision!

Questions to Ask Before Participating in Clinical Trials

Benefits of clinical trials for participants

Clinical trials can offer certain advantages for patients when compared to standard medical care and treatments. When considering participating in a clinical trial, it is important to weigh any benefits against the potential risks.

Benefits include:

• You may have access to completely new drugs and treatments. Some of these treatments may not be available to the general population at the time of the trial, as well as for years after the trial.
• When participating in a clinical trial, you will be closely monitored to determine any side effects. This results in a very high level of care, ensuring any adverse effects are treated quickly.
• Clinical trials effectively put your treatment in your own hands, giving you the option to seek alternative treatments when standard treatments are proving ineffective.
• Making a valuable contribution to scientific and medical research, potentially helping people across the world receive better treatment outcomes.

Risks of clinical trials for participants

Due to the experimental nature of some treatments that are being studied in clinical trials, there are risks that participants should be aware of.

Minor side effects and slight discomfort cannot be ruled out in some trials, especially those that involve a surgical procedure. Participants could experience complications that may require further medical attention, and, in sporadic cases, treatment may even result in serious, long-term, or even life-threatening complications.

Compared to standard treatment, a clinical trial may also require a higher level of commitment and time from participants. This could be because regular visits to the study site are required for consultations, issuing feedback, and blood tests. A person may also need additional procedures, hospital stays, and more complex dosage schedules in line with the trial’s design.

Other clinical trial risks include:

• The alternative treatment may prove ineffective, with no apparent benefits
• The treatment may result in side effects that can range in severity
• The treatment may work for others but not for you
• Study procedures may be more demanding than standard care
• Clinical trials can sometimes have unknown risks
• There may be unexpected costs while participating in a trial

Are some phases of clinical trials riskier than others?

Clinical trials are conducted in phases, with each phase carrying a slightly different level of risk. In each phase, researchers assess the safety of the intervention to determine the correct dosage and to identify possible side effects.

The number of participants in each trial can differ considerably, with the early stages typically evaluating smaller group sizes.

• Phase I - Phase I trials often have the highest level of potential risk as the treatment is still in its very early stages. However, some participants have been known to greatly benefit from phase I trials.
• Phase II - Larger participation groups are selected for phase II trials which often result in fewer side effects thanks to the data gathered in phase I, reducing the level of risk.
• Phase III - The group sizes are increased again in phase III trials, usually assessing at least several thousand individuals. The third phase is considered even less risky as the treatment has already passed two robust testing periods. The risk factor is further reduced as Data Safety Monitoring Boards are also introduced at this stage for added regulation.

How do researchers ensure the safety of clinical trials?

To ensure a high level of safety, trials are subject to regulations, with processes in place to minimize risk. For example, continuous close monitoring of all participants is one of the key methods of assuring health and safety standards.

During the trial, researchers will also follow the 5 steps listed below to enhance the safety of the study.

1. Devise a research plan, referred to as the protocol
2. Form an institutional review board (IRB)
3. Form a data and safety monitoring board (DSMB).
4. Obtain informed consent from all participants
5. Report the results of the trial to the Department of Food and Drug Administration (FDA) or the European Medicines Agency (EMA).

Protocols

The protocol of the clinical trial is a document that provides a detailed outline of how the trial will be conducted. This includes the objective(s), design, methodology, and any statistical considerations of the study. The protocol also outlines the steps that will be taken to ensure the safety of participants and the integrity of any data that is collected.

A clinical trial protocol will typically include the following information:

• How participants will be fully informed of all details of the trial
• The overall purpose and objective of the trial
• How the researchers will conduct the study
• The types of volunteers that will be required
• How the safety of participants will be monitored
• What medications, devices, and methods will be used during the trial
• The type of data and information that will be collected
• The duration and schedule of the trial

Institutional Review Board

An Institutional Review Board (IRB) is a group formed to review and monitor a clinical trial that involves human participants. Before the trial can commence, an IRB will review and approve the trial’s protocol and research plan.

An IRB typically consists of doctors, nurses, scientists, patient advocates, members of the clergy, statisticians, and other professionals. Their role is to ensure the clinical trial is safe and completely ethical, considering all human rights of the participants, staff, and volunteers in the clinical trial.

In the US, an IRB is required to approve clinical studies that receive financial support from federal research funds or are seeking FDA approval before any patients can be enrolled.

The key objectives of an Institutional Review Board are to:

• Ensure the study is ethical
• Ensure any risk to participants is kept to a minimum
• Ensure the rights and welfare of the participants are protected
• Ensure participants have given informed consent and understand all aspects of the clinical trial.

Data Safety Monitoring Board

Along with an IRB, a Data Safety Monitoring Board (DSMB) must also be set up for most clinical trials. This is a group of individuals who are experts in relevant fields of study and are completely independent of the research team. The final results of a clinical trial are not typically released until the study is finished and all the data has been analyzed by the DSMB.

The DSMB will review the data that is collected during a trial, or multiple trials, providing the trial sponsor with information such as the continued safety of the trial participants, the validity of the trial, and the scientific merit of the trial. The DSMB has the authority to pause or end the trial if there are any safety or ethical concerns.

Safety monitoring is integral to a clinical trial but not all trials require a DSMB, clinical trials that must have a Data Safety Monitoring Board include:

• Trials designed to save lives
• Trials that reduce the risk of serious side effects
• Long-term trials that monitor the safety of medical interventions, even those for conditions that are non-life-threatening.

Informed consent

Informed consent refers to the process of an individual learning about all aspects of a clinical trial before agreeing to participate in it. It is up to the clinical trial’s research team to explain all the details of the trial. This includes its purpose, duration, benefits, risks, the trial’s format and schedule, and any data privacy considerations regarding medical records.

If you decide to participate in a clinical trial, you will be given a document containing all of this information so you can refer to it at any time. Once you have fully understood this information, you will then be able to give informed consent to enroll in the study. During the informed consent stage, you will also receive information relating to the following:

• The medical interventions or procedures you will undergo
• The clinical trial’s protocol and overall design
• Details regarding possible risks, side effects, and discomfort
• Confirmation that the trial is completely voluntary and how you can end participation

The Food and Drug Administration

The FDA plays a key role in US-based clinical trials, making sure that participants are provided with the relevant information before they choose to join a study. The FDA ensures that the regulations and guidelines set out by the Federal Government are adhered to, guarding individuals from potential risks and protecting their safety. Ultimately, preserving the welfare of all participants is at the core of the FDA’s role during clinical trials.

What is the FDA’s role in approving new drugs and medical treatments?

The FDA is responsible for ensuring medical treatments are safe and effective before they are introduced to the general population. The administration oversees clinical trials to monitor their design and conduct and to check that the results are analyzed and reported correctly, according to federal law and good clinical practice (GCP) regulations.

The FDA plays no part in the development of new therapies, nor does it conduct clinical trials, Instead, the FDA governs clinical trials across the country, consulting with researchers, performing inspections of the study sites, protecting the rights of patients, and verifying the quality and integrity of all data that is collected.

European Medicines Agency

If a clinical trial is to be included in an application to gain marketing authorization for human medicines in the European Union (EU)/ European Economic Area (EEA), then the trial must adhere to Annex 1 of Directive 2001/83/EC requirements - even if the trial is conducted in the US or anywhere else outside of the EU.

According to the Annex 1 of Directive 2001/83/EC:

• Clinical trials conducted within the EU/ EEA must comply with EU clinical trial legislation
• Clinical Trials conducted outside of the EU/ EEA must comply with ethical principles that are equivalent to those set in the EEA. This includes complying with the international good clinical practice and the Declaration of Helsinki

What is EMA’s role in approving new drugs and medical treatments?

EMA's Committee for Medicinal Products for Human Use (CHMP) carries out the assessment of human medicine for clinical trials that seek EU-wide marketing authorization.

This includes a scientific evaluation that reviews the clinical trial data that must be included in the clinical study reports as part of the wider application. All assessments are based on scientific criteria that evaluate whether a medicine meets the required quality, safety, and efficacy requirements according to EU legislation.

In addition, the EMA also manages two clinical trial databases, EudraCT and the Clinical Trial Information System, and co-manages the business change program Accelerating Clinical Trials in the EU (ACT EU), together with the Heads of Medicines Agencies (HMA) and the European Commission.

Trial reporting

Clinical trial researchers must report certain data to ClinicalTrials.gov, this is an online database in the US that keeps a record of clinical trials that have been conducted and their various outcomes. This enables better transparency in the clinical research field, allowing individuals to read about previous clinical studies before choosing whether to participate or not.

Innovations in the safety of clinical trials

Clinical trials have significant scope for integrating new medical advancements into future research. However, researchers are challenged in terms of ensuring patient safety while testing these untried technologies. Safety concerns are the cause of some clinical trials failing to meet their objectives. In a recent study that analyzed phase III trials, 17% failed due to patient safety issues.

Two core areas for improving patient safety in the future are data-driven decision-making and the integration of technological advancements.

Data-driven decision making

Clinical trials that are powered by data-driven decision-making are much more likely to ensure patient safety and well-being. This is because data provides a greater level of analysis, allowing researchers and medical teams to identify any safety concerns at their inception to provide a quick intervention and mitigate any risks.

Additionally, data-driven insights can also create more adaptive trials that can easily be changed and adjusted depending on the latest data. For example, the trial can be optimized based on information such as variations in patient responses. With this data, personalized care can be given to specific patients, and treatments/dosages can be adjusted. This allows trials to become safer and more effective, delivering the highest possible standards to patients.

Technological advancements

Deploying the latest monitoring tools such as wearables and remote monitoring devices makes it possible for researchers to implement continuous health tracking which can deliver real-time safety assessments and interventions.

The use of artificial intelligence and advanced data analytics can also detect any safety concerns early in the study. Analyzing large data sets to detect unusual patterns and unexpected results. This technology can also play a key role in the development of new drugs, highlighting safety concerns and suggesting personalized treatments based on the patient’s profile.

Telehealth is a remote consultation solution that reduces the required amount of in-person visits, making participating in a clinical trial more convenient. This is also an invaluable tool should there be a public health crisis, such as we saw during the COVID-19 pandemic.

Electronic Health Records (EHRs) provide a centralized database of patient information to improve the accuracy and accessibility of data. This facilitates more coordinated care solutions and can significantly boost patient safety. The introduction of communication platforms and collaboration tools also makes it easier to share patient information to deliver improved care.

Finally, state-of-the-art simulation and training tools can better prepare and educate healthcare professionals to increase their ability and experience so they can better manage patient safety.

The future of patient safety in clinical trials

Artificial intelligence, machine learning, and automation are expected to play a significant role in the future of patient safety in clinical trials. This groundbreaking technology will give researchers access to insights that were not previously possible, revolutionizing the field of medical science and how safety measures are implemented in clinical trials.

Clinical trial automation

The use of technology can accelerate the introduction of innovative new approaches, resulting in improved patient safety. Automation can remove the need for staff members to complete time-consuming and tedious tasks, instead focusing on identifying risks and potential improvements that could be made.

In a 2021 State of Industry Report, compiled by ArisGlobal, data showed that 83% of the life sciences industry is now leveraging automation tools in some way. Automation is predominantly used in terms of research and development, increasing overall productivity and reducing time-to-market. This figure is expected to grow even further as more and more organizations realize the potential of automated processes.

Data collection and analysis

The collection, analysis, and interpretation of data are essential in delivering patient safety. This applies to both current practices and those in the future. The use of advanced data sets can help to deliver more accurate predictions when assessing patient behaviors, allowing researchers to design clinical trials accordingly.

Meanwhile, continuous data analysis enables real-time monitoring allowing researchers to perform comprehensive and ongoing risk assessments throughout the clinical trial.

Clinical trial decentralization

Decentralized clinical trials (DCTs) are becoming more popular due to their convenience and reduced risk level. At times when participants cannot visit the study site in person, remote consultation platforms can make sure the timeline of the clinical trial is unaffected.

Should a patient be considered higher risk, decentralization makes participation easier, improving retention rates, and ensuring all individuals are safe.

Conclusion - Is it safe to participate in a clinical trial?

To guarantee that clinical trials are as safe as possible, researchers must follow a wide range of regulations and guidelines. Each trial is assessed by an institutional review board, data safety monitoring board, and the FDA, with trials paused or canceled if safety standards are not met.

This level of scrutiny ensures that the safety and well-being of participants are the primary concern, giving individuals access to new treatments before they reach the market. However, before choosing to participate in a clinical trial, you must determine the risks and benefits of the study, as well as understand what is required of you.