Preclinical Trials vs Clinical Trials

Before a new intervention can be tested in human clinical trials, it undergoes extensive preclinical testing to evaluate its safety and efficacy.

Preclinical trials are a critical step in product development. They provide valuable information about a potential treatment's pharmacology, toxicology, and mechanism of action.

Learn the differences between preclinical and clinical trials to understand the rigorous scientific process behind bringing new medicines from the lab bench to the subject's bedside.

Table of Contents:

• Overview of Preclinical Trials
• Phases of Preclinical Trials
• Overview of Clinical Trials
• Phases of Pharmaceutical Clinical Trials
• Stages of Nutraceutical and Medical Device Trials
• Differences Between Preclinical and Clinical Trials
• Transitioning from Preclinical to Clinical Trials
• Challenges in Preclinical and Clinical Research
• Strategies for Successful Preclinical and Clinical Trials
• Key Takeaways
• Conclusion
• FAQs

What are Preclinical Trials?

Preclinical trials are research studies conducted before a new treatment is tested in humans. These studies assess a potential treatment's safety, toxicity, pharmacokinetics (how the body processes the product), and pharmacodynamics (how the product affects the body).

The main objectives of preclinical trials are to:

• Determine if a product is safe enough for human testing: Preclinical studies help identify potential toxicity or adverse effects of a new product and establish safe dosing ranges for human trials.
• Evaluate a product's efficacy: Preclinical trials provide initial evidence of a product's effectiveness in treating a particular disease or condition, often using animal models or in vitro systems.
• Understand a product's mechanism of action: Preclinical studies help elucidate how a product works at the molecular and cellular level, providing insights into its potential therapeutic benefits and limitations.

Examples of Preclinical Trials

Preclinical trials encompass a wide range of studies, each designed to answer specific questions about a potential new product or treatment. Some common examples include:

• In vitro studies: These are conducted in a controlled setting (labs) using cell cultures or isolated tissues. They can help identify a product's effects on specific biological processes or disease pathways.
• In vivo animal studies: These involve testing a product in animal models, such as mice or rats. Animal studies provide valuable information about a product's safety, efficacy, and pharmacokinetics in a living system.
• Toxicology studies: These evaluate a product's potential toxicity, including its effects on vital organs, reproductive function, and overall health. They help establish safe dosing ranges and identify any possible adverse effects.
• Pharmacokinetic and pharmacodynamic studies: These investigate how a product is absorbed, distributed, metabolized, and excreted by the body (pharmacokinetics) and how the product affects the body's biological processes (pharmacodynamics). This information is critical for designing safe and effective dosing regimens for human trials.

Phases of Preclinical Trials

Preclinical trials typically progress through several phases, each with specific goals and objectives. 

Discovery and Development

The first phase of preclinical trials identifies potential product targets and develops lead compounds that can effectively interact with those targets. Researchers use various techniques, such as high-throughput screening and computer-aided drug design, to identify promising molecules that may have therapeutic potential.

Once a lead compound is identified, it is optimized to improve its potency, selectivity, and pharmacokinetic properties. This process may involve modifying the molecule's chemical structure, testing different formulations, and evaluating its stability and solubility.

Preclinical Testing

What does pre-clinical testing entail?

• Safety and toxicity assessment: Before a new product can be tested in humans, it undergoes extensive safety and toxicity testing in preclinical models. This evaluates the product’s effects on vital organs, e.g., the liver and kidneys, and assesses its potential for causing congenital disabilities or cancer. These studies help establish a safe starting dose for human trials and identify potential risks.

• Pharmacology and efficacy studies: Preclinical pharmacology and efficacy studies evaluate how well a product manages a disease or condition. These studies often involve testing the product in animal models that closely mimic human disease, such as genetically modified mice or rats. Researchers assess various endpoints, such as tumor growth, inflammation markers, or behavioral changes, to determine the product's potential therapeutic benefits.

• Formulation and stability testing: Developing a stable and effective formulation is crucial for ensuring a product’s safety and efficacy in human trials. Preclinical formulation studies evaluate different product delivery methods, such as oral, injectable, or topical formulations, and assess their stability under various storage conditions. This ensures the product remains active and consistent throughout the clinical trial.

Investigational New Drug (IND) Application

After preclinical testing, researchers prepare and submit an Investigational New Drug (IND) application to regulatory authorities, such as the FDA in the United States or the EMA in Europe. 

The IND application includes detailed information about the product’s preclinical safety and efficacy data and plans for proposed human clinical trials.

Regulatory authorities review the IND application to ensure that the product is safe for human testing and that the proposed clinical trials are scientifically sound and ethically justified. If the IND is approved, the product can advance to Phase 1 clinical trials, marking the transition from preclinical to clinical development.

What are Clinical Trials?

Clinical trials are research studies conducted in human volunteers to evaluate the safety, efficacy, and optimal use of products, devices, or procedures. 

These trials are critical in product development because they provide evidence to determine whether a new therapy is safe and effective for patients.

The primary objectives of clinical trials are to:

• Assess the safety and tolerability of a new treatment in humans.
• Determine the most effective dose and schedule for a new treatment.
• Evaluate the efficacy of a new treatment compared to existing standards of care or placebo.
• Identify any potential side effects or adverse reactions associated with a new treatment.
  
  

Phases of Pharmaceutical Clinical Trials

Drug trials are typically conducted in four phases, each with specific goals and objectives:

Phase 1 trials: These are the first studies conducted in humans, usually involving a small group of healthy volunteers. The primary goal of Phase 1 trials is to assess the safety, tolerability, and pharmacokinetics of a new product and determine the maximum tolerable dose.

Phase 2 trials: Once a product is safe in Phase 1, it moves to Phase 2 trials, typically involving more participants with the condition or disease being studied. The main objectives of Phase 2 trials are to evaluate further the product's safety and efficacy and to determine the optimal dose for Phase 3 trials.

Phase 3 trials: Large-scale, randomized, controlled trials that compare the new treatment to existing standards of care or placebo. These trials involve hundreds to thousands of participants and are designed to provide definitive evidence of a product's safety and efficacy. 

If successful, the results of Phase 3 trials can be used to support a New Drug Application (NDA) for FDA approval.

Phase 4 trials: Also known as post-marketing surveillance studies, Phase 4 trials are conducted after a drug has been approved and marketed. 

These studies monitor the product’s long-term safety and effectiveness in real-world settings and identify rare or long-term side effects that may not have been detected in earlier trials.

Stages of Nutraceutical and Medical Device Trials

Nutraceutical and medical device trials, while not conducted in the same phased manner as pharmaceutical trials, follow a structured approach divided into pilot and pivotal stages. Each stage has distinct objectives tailored to ensure the safety, efficacy, and regulatory compliance of the product under investigation.

Nutraceutical Trials

Pilot Trials: Pilot trials for nutraceuticals are initial, small-scale studies involving a limited number of participants. The primary objectives of pilot trials are to:

1. Assess Safety: Evaluate the short-term safety profile of the nutraceutical product.
2. Determine Feasibility: Establish the practicality of conducting larger-scale studies, including participant recruitment and adherence to the study protocol.
3. Preliminary Efficacy: Gather early data on the potential health benefits and efficacy of the nutraceutical.
4. Dosage Optimization: Identify the appropriate dosage range for future studies.

Pivotal Trials: Pivotal trials are larger, more definitive studies designed to provide robust evidence regarding the nutraceutical's efficacy and safety. The main objectives include:

1. Confirm Efficacy: Provide statistically significant data demonstrating the health benefits of the nutraceutical.
2. Safety Profile: Confirm the safety of the product over a longer duration and in a larger population.
3. Regulatory Submission: Generate comprehensive data required for regulatory approval and marketing claims.
4. Market Viability: Assess the product's effectiveness in a real-world setting, including consumer acceptability and compliance.

Medical Device Trials

Pilot Trials: Pilot trials for medical devices involve a small group of participants and are aimed at evaluating the initial performance and safety of the device. The primary goals are to:

1. Evaluate Safety: Assess the immediate safety concerns and any potential risks associated with the device.
2. Technical Performance: Verify that the device functions as intended in a controlled setting.
3. User Interaction: Collect feedback from users and healthcare professionals on the device's usability and any operational issues.
4. Protocol Validation: Refine the study protocol for subsequent larger trials.

Pivotal Trials: Pivotal trials for medical devices are extensive studies involving a larger population, designed to provide conclusive evidence of the device's efficacy and safety. The key objectives are to:

1. Demonstrate Efficacy: Show that the device provides the intended health benefits effectively.
2. Long-term Safety: Monitor and document the long-term safety of the device across a broader and more diverse population.
3. Comparative Analysis: Compare the device to existing standard treatments or devices to establish its relative effectiveness.
4. Regulatory Approval: Collect and present the data necessary for regulatory bodies to approve the device for market use.

Both nutraceutical and medical device trials play a crucial role in bringing safe and effective products to market, ensuring they meet the necessary standards for consumer use. By following structured pilot and pivotal stages, researchers can systematically address safety and efficacy concerns, paving the way for successful regulatory approvals and market introductions.

Key Differences Between Preclinical and Clinical Trials

Preclinical and clinical trials are objectively different scientific exercises; here’s how they differ:

Study Subjects

Preclinical trials involve testing in vitro models, such as cell cultures or isolated tissues, and in vivo animal models, like mice or rats. 

These models help researchers understand the product's effects on specific biological processes or disease pathways and provide valuable information about safety, efficacy, and pharmacokinetics in a living system. 

In contrast, clinical trials involve human participants, allowing researchers to evaluate the product's safety, tolerability, and effectiveness directly in the target population.

Objectives

The primary objectives of preclinical trials are to assess a new treatment's safety, toxicity, and efficacy before it can be tested in humans. 

These studies help identify potential adverse effects, establish safe dosing ranges, and provide initial evidence of the product's effectiveness in treating a disease or condition. 

On the other hand, clinical trials evaluate the safety, efficacy, and optimal dosing of a new treatment in human volunteers. They provide the necessary evidence to determine whether a new therapy is safe and effective for widespread patient use.

Regulatory Requirements

Preclinical trials are conducted under Good Laboratory Practice (GLP) regulations, which ensure the quality, integrity, and reliability of non-clinical laboratory studies. GLP regulations cover various aspects of preclinical research, including study design, data collection, and reporting. 

In comparison, clinical trials are subject to Good Clinical Practice (GCP) guidelines. These are international ethical and scientific quality standards for designing, conducting, recording, and reporting trials that involve human participants. 

GCP guidelines protect participants' rights, safety, and well-being, as well as the credibility and accuracy of clinical trial data.

Duration and Cost

Preclinical trials are generally shorter and less expensive than clinical trials. Depending on the complexity of the research and the specific objectives, preclinical studies can last a few weeks to several months. 

Preclinical trials also require fewer resources, as they involve smaller-scale experiments and do not require the extensive infrastructure and personnel needed for human studies. 

In contrast, clinical trials are longer and more costly, particularly in the pharmaceutical space. Drug trials often span several years and involve hundreds to thousands of participants. Nutraceutical trials and lower risk medical device trials are generally much shorter than this however, spanning months rather than years with participant number ranging from 50 to 500 rather than thousands. The expenses associated with traditional onsite clinical trials include participant recruitment, medical staff, facilities, and the development of complex protocols to ensure participant safety and data integrity. Newer trial model,s such as hybrid and remote trials, help to reduce these costs by reducing the staffing costs and employing digital technology to improve efficiencies.

Transitioning from Preclinical to Clinical Trials

A seamless transition from preclinical to clinical trials is vital for successfully translating promising product candidates into approved therapies. This process involves several key considerations to ensure the knowledge gained from preclinical studies effectively informs the design and execution of human trials.

Robust Preclinical Data

A solid preclinical safety and efficacy data foundation is essential to justify the progression to human studies. It includes comprehensive toxicology studies, pharmacokinetic and pharmacodynamic assessments, and proof-of-concept efficacy data in relevant animal models.

Regulatory Compliance

Navigating the complex regulatory landscape is crucial for a smooth transition to clinical trials. This involves preparing and submitting an Investigational New Drug (IND) application to regulatory authorities, including detailed information about the product's preclinical safety and efficacy data and plans for proposed human trials.

Clinical Trial Design

Scientifically sound and ethically justified clinical trials are critical for a successful transition. This means selecting appropriate study endpoints, determining optimal dosing and administration routes, and developing robust protocols to ensure participant safety and data integrity.

Partnering With Experienced CROs

Collaborating with contract research organizations (CROs) specializing in clinical trials can facilitate the transition process. These CROs offer expertise in clinical trial design, regulatory compliance, participant recruitment, and data management, ensuring a seamless and efficient progression from preclinical to clinical development.

Atlantia Clinical Trials is a world-leading CRO specializing in groundbreaking clinical trials for nutraceuticals, pharmaceuticals, cosmetic products, and medical devices. 

We are experts in managing various types of human clinical studies and stay with you every step of the way. Whether you want to obtain proof of efficacy, substantiate a health claim, or simply gather clinical evidence to support your sales and marketing, we are here for you.

Challenges in Preclinical and Clinical Research

Preclinical Challenges:

Limitations of animal models: While animal models provide valuable insights into disease mechanisms and product efficacy, they may not accurately predict human responses.

Differences in anatomy, physiology, and genetics between animals and humans can lead to discrepancies in product metabolism, toxicity, and effectiveness. 

Overcoming these limitations requires carefully selecting appropriate animal models and advanced techniques, such as humanized mouse models or organ-on-a-chip technologies.

Reproducibility and translatability issues: Preclinical studies sometimes suffer from poor reproducibility, which can hinder the successful translation of findings to human trials. 

This can be due to inadequate study design, lack of standardization in experimental protocols, or publication bias towards positive results. 

Addressing these issues involves implementing rigorous quality control measures, promoting data sharing and transparency, and encouraging the publication of negative or inconclusive results.

Clinical Challenges:

Participant recruitment and retention: Recruiting and retaining participants is a significant challenge in clinical trials. 

Factors such as strict eligibility criteria, geographic limitations, and the time commitment required for participation can make enrolling sufficient participants difficult. 

Overcoming these challenges may involve using innovative recruitment strategies, such as social media campaigns or patient advocacy group partnerships, and offering incentives and support to encourage participant retention throughout the trial.

Ensuring data quality and integrity: Maintaining high-quality data is essential for the validity and reliability of clinical trial results. This involves implementing robust data collection and management processes.

It also means training research staff to ensure consistent and accurate data entry. Regular monitoring and auditing of trial data can help identify and address any data quality or integrity issues.

Regulatory compliance: Navigating the complex regulatory landscape is a significant challenge in clinical research. 

Complying with Good Clinical Practice (GCP) guidelines and other regulatory requirements involves developing comprehensive study protocols, obtaining ethical approvals, and maintaining detailed documentation throughout the trial. 

Collaborating with experienced partners, such as contract research organizations or regulatory consultants, can help streamline the compliance process and minimize the risk of regulatory delays or setbacks.

Strategies for Successful Preclinical and Clinical Trials

Implementing robust strategies for these trials ensures that potential treatments are thoroughly vetted, leading to successful outcomes and patient benefits.

Select the Most Appropriate Models for Your Research

Choosing the right research model is critical to generating reliable and translatable preclinical data. When selecting models, consider factors such as genetic background, disease relevance, and predictive validity. 

For clinical trials, carefully define your target population and inclusion/exclusion criteria to ensure your study cohort accurately represents the intended patient group.

Ensure Your Study Has Adequate Statistical Power

Conducting a power analysis during the planning stage helps determine the sample size needed to detect meaningful treatment effects. 

Underpowered studies risk missing important findings, while overpowered studies waste resources. Work with a statistician to design a study with sufficient power to answer your research questions.

Adhere to Established Protocols and Guidelines

Following standardized protocols and GLP/GCP guidelines ensures the quality, integrity, and reproducibility of your research. Develop clear, detailed protocols and train your research team to execute them consistently. Regular monitoring and auditing can help identify and address any deviations or issues.

Assemble a Skilled and Experienced Research Team

A knowledgeable, well-trained research team is essential for successful preclinical and clinical trials. Ensure your team has expertise in study design, data collection, and regulatory compliance. Provide ongoing training and support to maintain high-performance standards.

Foster Effective Collaboration and Communication

Collaborating with partners with complementary expertise can significantly enhance the success of your research. Establish clear lines of communication and data-sharing protocols to ensure seamless coordination among team members. Regular meetings and progress updates can help identify and resolve challenges or bottlenecks.

Partnering with a CRO specializing in clinical trials, like Atlantia Clinical Trials, can provide valuable support throughout the research process. These organizations offer expertise in study design, regulatory compliance, and data management, allowing you to focus on the scientific aspects of your research.

Choosing the Right Partner for Your Clinical Trials

Working with an experienced and reliable CRO significantly improves the probability of success of your clinical trials. A skilled CRO partner helps you navigate the complex clinical research landscape, ensuring regulatory compliance, efficient study execution, and high-quality data.

When choosing a CRO, consider their expertise in your area of interest. Your partner should have a proven track record of successfully conducting similar trials, be it medical devices, dietary supplements, cosmetics, or community-based drugs. 

Another critical factor is the CRO's ability to provide comprehensive support throughout the clinical trial process. This includes assistance with protocol development, regulatory submissions, site selection and management, participant recruitment and retention, data management, and statistical analysis. 

Also, think about flexibility and adaptability. Your CRO should be able to tailor their services to your specific needs and goals. They should be open to collaboration and willing to adapt their approach as your research evolves. This flexibility ensures that your trial remains on track and aligned with your objectives.

Effective project management is vital for the smooth execution of clinical trials. Your CRO should have dedicated project managers who can coordinate all aspects of your study, from planning to closeout. 

They should provide regular updates and proactively address issues to keep the trial on schedule and within budget.

Ultimately, the quality and integrity of your clinical trial data is paramount. Your CRO partner should have robust quality assurance processes, including regular monitoring and auditing of study sites and data. They should also have systems for detecting and managing potential data discrepancies or protocol deviations.

Lastly, effective communication and collaboration between you and your CRO are essential for a successful partnership. Establish clear lines of communication from the outset, with regular meetings and progress reports. Foster a culture of transparency and open dialogue, allowing for timely resolutions of challenges or concerns.

Conclusion

Understanding the complexities of clinical trials can be challenging, but Atlantia Clinical Trials simplifies this process, guiding you every step of the way. Our expertise and comprehensive support make your journey from the lab to the market more streamlined and effective. 

Partner with Atlantia Clinical Trials for expert guidance to clinical success.

FAQs

Why are Preclinical Trials important?

Preclinical trials are crucial for identifying potential toxicity, establishing safe dosing ranges, and providing initial evidence of a product's effectiveness before it is tested in humans.

What Types of Studies are Included in Preclinical Trials?

Preclinical trials include in vitro studies (cell cultures or isolated tissues), in vivo animal studies (testing in animal models), toxicology studies, and pharmacokinetic/pharmacodynamic studies.

What is the Purpose of Toxicology Studies in Preclinical Trials?

Toxicology studies evaluate a product's potential toxicity, including its effects on vital organs, reproductive function, and overall health, to establish safe dosing ranges and identify possible adverse effects.

How Do Preclinical Trials Differ from Clinical Trials?

Preclinical trials involve testing in vitro models and animal models to assess safety, efficacy, and pharmacokinetics, whereas clinical trials involve human participants to evaluate the product's safety, tolerability, and effectiveness.

What are Some Challenges in Preclinical Research?

Challenges include the limitations of animal models, reproducibility and translatability issues, and ensuring robust preclinical data to justify human studies.