Data is the cornerstone of any clinical trial and is used to ultimately drive the decision-making process related to the drug development. The quality of your clinical evidence package is an important factor in gaining approval from key decision-makers, including regulators, payers, and health technology assessment (HTA) agencies. So, how can you generate high-quality clinical data, especially when you don’t have the appropriate in-house expertise?
How to Ask the Right Questions at an Authority Meeting
As a drug developer, you have to live with the answers and comments you get from regulatory authorities. Therefore, it’s essential that you choose your questions carefully and avoid questions you don’t need answers to. Let’s take a closer look at how to approach these meetings: Read more »
How to Create and Optimize a Clinical Development Plan
A clinical development plan — a comprehensive strategy for developing an investigational product through regulatory submission — is a critical component of drug development and helps ensure that new therapies are safe, effective, and of high quality. Here, I offer a high-level overview on steps to take to create a clinical development plan, how to optimize your plan as the program progresses, and why this comprehensive roadmap is so vital to the success of your development program.
How to create a clinical development plan
Creating a clinical development plan typically involves a multidisciplinary team that includes experts in clinical development, regulatory affairs, medical affairs, statistics, and other relevant areas. Consider the following steps when creating a clinical development plan:
- Target identification: The first step in creating a clinical development plan is to identify a target disease or condition that the drug is intended to treat.
- Preclinical testing: Preclinical testing is then conducted in animal models to assess the drug’s safety and efficacy and determine the appropriate dose levels for use in human clinical trials.
- Biomarker identification (if applicable): Determine what sort of biomarkers are planned to be assessed, and which of the seven categories the putative biomarker(s) fit into, e.g., diagnostic, prognostic, pharmacodynamic, or safety.
- Phase I clinical trial design: The design of the Phase I clinical trial is then determined, including the number of subjects to be enrolled, the dose levels to be tested, and the endpoints to be measured. Work closely with clinical pharmacologists/toxicologists to optimize dosing evaluation and modeling for this Phase.
- Phase II clinical trial design: Based on the results of the Phase I trial, the design of the Phase II clinical trial is determined. At this point, the efficacy assessments, endpoints, and applicable estimands should be determined. The safety assessments should be refined based on any information gathered from the Phase I study as well as pre-clinical information.
- Phase III clinical trial design: Based on the results of the Phase II trial, the design of the Phase III clinical trial is determined, including the number of subjects to be enrolled, the estimands, and the endpoints to be measured. These trials are likely to be the most extensively described in the future package insert, so you want to be sure that they make a clear and convincing argument for why your product should be administered to the desired population in the tested manner in order to get the desired efficacious response.
- Data analysis: Plans for data analysis are developed, including statistical methods and procedures for ensuring data quality.
- Regulatory interactions: Plans for interacting with regulatory agencies, including submitting regulatory filings and conducting meetings with regulatory authorities, are developed.
- Safety monitoring: Plans for monitoring the drug’s safety during clinical development and after it is approved for use are developed.
- Pediatric study plans are developed, as required by US and EU authorities. These plans must address treatment for persons from 0-18 years old, though waivers may be granted for certain subsets and for certain products. These plans should be planned early on. It is best not to delay the planning until late in Phase III.
The clinical development plan is then reviewed and revised as needed to ensure that it meets regulatory requirements, addresses safety concerns, and provides a clear roadmap for the clinical development of the drug. The plan is a living document, updated regularly as new data becomes available and the development program progresses.
How to optimize your clinical development plan
Optimizing a clinical development plan involves making adjustments to ensure that the development program is designed to achieve the best possible outcome while minimizing risks and costs. It will involve expert input, careful consideration of the available data, and a willingness to adjust the plan as needed. Consider the following steps:
- Conduct a thorough review: The first step to optimize a clinical development plan is to thoroughly review the existing plan, including the available data and the regulatory landscape. This will help identify areas that need improvement or adjustment.
- Consult with experts: Consult with experts in relevant areas, including clinical development, regulatory affairs, medical affairs, and statistics, to obtain their input and recommendations.
- Refine the target population: Refine the target population by conducting additional analysis of patient demographics, disease characteristics, and other relevant factors to identify subgroups of patients that may benefit most from the drug.
- Optimize the trial design: Optimize the trial design by adjusting the sample size, the number of study arms, and the selection of endpoints to increase the chances of demonstrating efficacy and safety.
- Use adaptive trial designs: Consider using adaptive trial designs that allow for changes in the trial design based on interim data analysis to maximize efficiency and flexibility.
- Incorporate biomarkers: Incorporate biomarkers into the trial design to identify patients most likely to respond to the drug and to monitor the drug’s efficacy and safety.
- Use real-world evidence (RWE): Consider incorporating RWE to optimize the study design, identify new patient populations, and enhance understanding of the drug’s real-world effectiveness.
- Optimize the regulatory strategy: Work with regulatory agencies to optimize the regulatory strategy, including selecting endpoints and developing a compelling benefit-risk profile.
The importance of the clinical development plan
A clinical development plan is an essential component of drug development because it provides a comprehensive roadmap for the clinical trials required to demonstrate the safety and efficacy of a new drug or therapy. A thorough clinical development plan will:
- Ensure safety: A clinical development plan outlines the steps required to assess the drug’s safety in humans. By conducting clinical trials in a structured and systematic manner, potential safety issues can be identified early in the development process, allowing appropriate steps to be taken to address them.
- Demonstrate efficacy: The clinical development plan outlines the steps required to demonstrate the efficacy of the drug in treating the target disease or condition. By conducting clinical trials in a structured and systematic manner, the drug’s effectiveness can be accurately assessed, and potential issues can be identified and addressed.
- Provide a regulatory roadmap: The clinical development plan outlines the steps required to obtain regulatory approval for the drug. By adhering to the plan, developers can ensure they meet the regulatory requirements for drug development, which can help speed up the approval process.
- Help manage resources: The clinical development plan provides a roadmap for allocating resources, including time, money, and personnel. By having a clear plan, developers can allocate resources more efficiently, reducing costs and maximizing the chances of success.
Interested in learning more?
Learn how to optimize your data strategy to drive success in clinical development with our new ebook, “Discover the Value of an Optimized Clinical Data Strategy”:
Developing a New Drug Candidate: From Nonclinical to First-in-Human
Thank you to Charlotta Gauffin, Chief Scientific Officer at Dicot, for joining us for our recent webinar, “The Road to First-in-Human Trials: Insights from a Real-World Example.”
Thoughtfully and carefully planned nonclinical studies help pave a smooth path toward first-in-human Phase 1 clinical trials. This involves a collaboration between all areas of nonclinical development, including CMC, toxicology, pharmacology, DPMK, and so on, and keeping in mind early a plan that all stakeholders agree to, but that can be amended as you go along, if needed. Here, we share how Cytel and Dicot worked together to conduct the nonclinical studies for the LIB-01 compound, a new drug candidate to target and treat erectile dysfunction, including prerequisites for keeping project plans, delivery of results, and dealing with the consequences of decisions made during the drug development. Read more »
Don’t Forget the Development of Your Placebo: Overcoming Common Obstacles
A clinical trial is usually performed using some kind of comparator. This could be another drug on the market, or a customized formulation with the same characteristics as the drug formulation to be tested in the clinical trial — a placebo. Here I delve into developing your placebo and how to overcome common obstacles.
Drug Manufacturer Auditing: Ensuring Quality, Control, and Safety
Chemistry, Manufacturing, and Controls (CMC) is a critical component of drug product development. As a Senior Consultant in Drug Development, I serve as a representative for sponsors with the Contract Development and Manufacturing Organization (CDMO). The CDMO manufactures drug substances or drug formulations for safety studies and investigational drugs for clinical trials. This is a long-term relationship.
But why you should audit the manufacturer? This is a question that often emerges when the sponsor intends to test the product in clinical trials.
Here I’ll expand on why sponsors should audit the CDMO as well as go into when and how to conduct this critical check in ensuring the quality and safety of your drug. Read more »
Erika Spens on Developing Your Regulatory Strategy
During drug development, a comprehensive regulatory strategy is key for saving time and money. There are many common mistakes drug developers make that can be avoided if they consider their regulatory strategy and adapt it over time. For this edition of Industry Voices, Erika Spens, Director of Regulatory Affairs at Cytel, shares her expert insight on shaping a regulatory strategy, its many benefits, and how various factors affect the road toward market authorization. Read more »
First-in-Human Drug Substance and Formulation: The Challenge of Achieving Flexibility and Quality
For nonclinical studies that precede Phase I, a drug formulation in high doses and concentrations is required. While entering Phase I, high flexibility is needed, often covering a wide dose range. In addition, the quality and stability of the drug formulation should be adequate for the purpose.
- Are there differences in what level of quality is expected for the active drug substance in each phase?
- What are the requirements of the drug formulation for non-clinical studies and Phase I studies?
- Do you need a placebo corresponding to the active drug product?
Let’s look at how to handle some of these questions. Read more »
Commercial and Open-Source Software Synergy for Clinical Trial Design
In an ever-changing clinical development environment, sponsors face many challenges when designing clinical trials. These challenges can range from shifting regulations to growing pressure for a rapid time-to-market, and the variety of challenges can complicate trial design requirements. A thorough evaluation of numerous parameters is required in order to choose the best fit or optimal study, and this has led to more complex and innovative clinical trial designs.
When designing trials, biostatisticians have a choice between two main tools: commercial software or open-source development. Both options can be utilized to effectively design a trial, but which approach is best? Here, we will discuss both options and make a case for why this does not need to be an either-or question, but rather a “combined capabilities” approach that integrates open-source and commercial software.
Comparative Effectiveness: Methods and Techniques for Better Decision-Making
Health technology assessment (HTA) submissions require cost effectiveness analyses based on comparative effectiveness studies of survival benefits vs. standard-of-care options in each specific geography. Ideally, these submissions are based on large, randomized control trials (RCTs), however, most new drugs approved in the last five years, specifically in oncology and rare diseases, are being approved based on small clinical trials, often un-controlled or single arm. Often, these trials do not have overall survival as the primary efficacy parameter.
Thus, the dilemma: comparative evidence is still required for HTA submissions, but traditional investigative methods are no longer suitable to support value proposition. So where do we go from here? Read more »