Core Characteristics of Clinical Trial Management

An Overview of the Core Elements and Challenges of Clinical Trial Management!

Clinical Trial Management is the process of organizing, creating, running, overseeing, and communicating clinical trials that test the safety and effectiveness of new drugs, devices, or interventions.

For effective and efficient management of a clinical trial, coordination the actions of different parties are of utmost significance, that includes but is not limited to sponsors, investigators, regulators, ethics committees, patients, and vendors, so that the trial achieves its goals and follows the relevant rules and norms.

The management of clinical trials also involves overseeing the data, quality, budget, and timeline of the trial, as well as dealing with any problems or challenges that may occur during the trial.

 Core Characteristics of Clinical Trial Management are:

 1.   Clinical Trial Protocol: Clinical trials are complicated and changing projects with many stages, locations, nations, and fields. Each trial has its own specific protocol, design, objectives, and results, as well as its own norms and ethical principles. Managing clinical trials demands a lot of skill, knowledge, and flexibility to deal with the intricate and diverse nature of clinical trials.

The inherent intricacy of clinical trials can be addressed by explicitly detailing and implementing the predetermined procedure. By filing a document that outlines the reasons, goals, design, methods, statistical analysis, and structure of a clinical trial, as well as the ethical guidelines that regulate the trial's performance, is called a clinical trial protocol, and it is one of the main elements of managing a clinical trial.

According to the FDA, a clinical trial protocol should include the following sections:

General Information: This section has the trial title, sponsor and investigators' name and address, investigational product name and details, trial phase, study sites, expected trial length, and protocol date and version.

Background Information: This section explains the scientific and medical reasons for the trial, including the existing knowledge and needs in the field, the possible advantages and hazards of the product under investigation, the laboratory and human data that justify the trial, and the assumptions and goals of the trial.

Trial Design: This section outlines the trial's design and plan, such as the trial type (e.g., randomized, controlled, blinded, etc.), the main and secondary endpoints and outcomes, the sample size and power, the eligibility criteria, the randomization and blinding methods, the treatment groups and assignment, the intervention and delivery, the allowed and disallowed drugs, the follow-up length and intervals, and the criteria for ending or leaving the trial.

Trial Procedures: This section describes the procedures and assessments for the trial, including the visits for screening, enrollment, baseline, intervention, follow-up, and end-of-study, the data collection and management, the lab and imaging tests, the adverse event reporting and monitoring, the quality assurance and control, and the interim analysis and stopping rules.

Statistical Methods: This section explains how the data will be analyzed, and the results of the trial measured, including the plan for data analysis, the statistical models and assumptions, how missing data and outliers will be handled, the analyses for subgroups and sensitivity, and the significance level and confidence intervals.

Ethics: This section explains the ethical rules and standards for the trial, such as obtaining consent, protecting data, compensating for harms, complying with the Good Clinical Practice and the law, getting approval from the Institutional Review Board or Ethics Committee, and registering and reporting the trial.

 2.   Quality: Quality of Clinical trials is a crucial factor in ensuring the accuracy, validity and reliability of trial outcome. Therefore, every step of the trial process must follow strict quality rules and supervision, through internal and external audit/regulatory systems. The trial must follow the protocol, the GCP guidelines, and the relevant rules and laws, and clinical trial management. For Instance, Clinical trials in the United States are supervised and regulated by the US Food and Drug Administration (FDA). The FDA has established various rules and standards that aim to guarantee the quality of clinical trials, and that clinical trial management should adhere to and follow.

A few of these rules and standards are:

CFR Title 21 Part 11: This regulation establishes the requirements and guidelines for electronic records and electronic signatures that are used in clinical trials. It safeguards the quality, reliability, and security of the data and documents that are created, stored, sent, and retrieved electronically during the trial. The regulation also outlines the measures and processes that should be followed to protect the electronic records and signatures from unauthorized use, alteration, or deletion.

CFR Title 21 Part 312: This rule regulates how to conduct clinical studies of experimental new drugs (INDs) that are for human use. It explains what the sponsors and researchers of the INDs have to do, such as getting the FDA's permission and feedback, sending the plan and changes, reporting harmful events and safety data, keeping records and reports, and protecting human participants. The rule also tells how and when the FDA will monitor and check the INDs.

CFR Title 21 Part 50: This regulation sets the rules and steps for getting and recording the informed consent of human subjects in clinical trials. It explains what informed consent should include, such as the aim, risks, benefits, options, privacy, payment, contacts, and freedom of choice in the trial. It also shows when and how the FDA or the IRB can waive or change informed consent.

CFR Title 21 Part 56: This rule explains the standards and procedures for IRBs that check and approve human trials. It describes how IRBs are set up, run, and work, and how the FDA registers and recognizes them. It also says what the IRBs need and how they review and approve trial plans, consent forms, changes, and ongoing review.

CFR Title 21 Part 54: This regulation deals with the possible conflicts of interest from the financial ties between the clinical trial sponsors and the researchers. It makes the sponsors report and certify any financial stakes or deals that the researchers or their family have with the sponsors, like owning shares, getting paid, having patents, getting royalties, or receiving grants. It also makes the FDA check and assess how these financial stakes or deals affect the trustworthiness of the trial data and the safety of the human participants.

CFR Title 21 Part 812: This regulation covers how to do clinical studies of devices for human use that are not approved yet. It explains the different types of devices, like ones that have high or low risk, or ones that do not need this regulation. It also tells the sponsors and investigators of the devices what they have to do, such as getting the FDA's OK and feedback, sending the plan and changes, reporting problems and safety data, keeping records and reports, and protecting the people in the studies. The regulation also shows how the FDA checks and oversees the devices.

GCP Guideline: This is an international standard for ethical and scientific quality in clinical trials. It gives a common framework and guidance for applying GCP principles and rules in clinical trials. It also explains the duties of the sponsors, investigators, monitors, auditors, IRBs, and regulators to ensure quality in clinical trials. The ICH made the guideline, and the FDA accepted it as an official guideline document.

 3.   Cost: Clinical trials are costly and demanding activities that need substantial support from the sponsors and the investigators. Clinical trial management should make the best use of the resources and reduce the waste and inefficiencies that might happen during the trial. Managing a clinical trial also requires overseeing and controlling the trial's budget and cash flow and informing the stakeholders of any changes or differences.

Some possible ways to budget and manage the cost of a clinical trial are:

a)   Perform a feasibility study before the trial begins to check the resources, sites, and participants for the trial are available and appropriate. Make a detailed and reasonable budget that includes all the likely expenses and backup plans for the trial, such as staff, equipment, materials, travel, overhead, and management costs. Compare the budget with the real costs and money movement of the trial, and tell the stakeholders about any differences or errors.

b)    Work with the sponsors, vendors, and sites to get the best deals and agreements for the trial, and steer clear of any hidden or extra costs or payments.

c)    Save costs by using strategies and practices like electronic data capture, central lab services, better site selection and recruitment, and fewer protocol changes and errors.

d)   Look for outside funding sources or grants to cover the trial's expenses, especially for trials that are non-profit or academic.

e)    Use existing resources and networks, such as clinical research organizations, consortia, or registries, to make the trial faster and easier and lessen the workload on the trial team. Prepare in advance for the trial completion and closing of the trial sites, and budget enough money for the data analysis, writing, and storage of the trial.

4.   Length: Clinical trials are complex and long projects that need to meet strict deadlines, goals, and milestones for success. Clinical trial management has to organize and schedule the trial's tasks and activities, and track and assess the trial's progress and performance. Managing clinical trials also involves addressing any problems that may affect the trial's speed and communicating any adjustments or news to the stakeholders.

Some of the top ways to determine the duration of clinical trial management are:

a) Use historical data, benchmarks, or simulation tools to estimate how long each phase and task of the trial will take, such as protocol development, site selection, recruitment, enrollment, intervention, follow-up, data collection, analysis, and reporting. Think about how the trial's design, complexity, population, location, and resources may influence the trial's length.

b) Plan and share clear and attainable deadlines and milestones for each trial phase and task with the trial team and the stakeholders. Use tools and methods like Gantt charts, critical path analysis, or PERT charts to schedule and monitor the trial. Change the deadlines and milestones as required based on how the trial goes.

c) Regularly and systematically check and assess how long the trial takes, using suitable measures and signs, such as how fast people join, how many stay, how good the data is, or how much time is needed. Solve any problems or delays that may make the trial longer, such as few recruits, many dropouts, protocol changes, bad events, or data mistakes. Tell and record any changes or updates in the trial's length to the trial team and the stakeholders.

 5.   Challenge: Clinical trials are unpredictable and precarious ventures that may face different obstacles and problems during the trial. Clinical trial management should identify and evaluate the possible risks and problems that could impact the trial, and apply suitable plans and measures to avoid or address them. Clinical trial management should also record and report any adverse events or deviations that may happen during the trial, and assess and learn from the results and feedback of the trial.

Some of the major risks and resolutions in clinical trial management are:

a)   Recruitment and retention of participants: Finding and keeping enough participants who qualify for and agree to follow the trial protocol is a frequent problem for clinical trials. This can influence the possibility, reliability, and applicability of the trial outcomes.

To deal with this risk, clinical trial management should use strategies for recruitment and retention that work well, such as checking who can join, giving clear information and consent forms, giving rewards and help, and keeping in touch and following up.

b)   Data Quality and Integrity: One more significant risk for clinical trials is to maintain the quality and integrity of the data obtained from the participants, the trial locations, and the laboratory tests. Data quality and integrity can be affected by human mistakes, incomplete values, anomalies, fraud, or bias. To reduce this risk, clinical trial management should follow strict rules and methods for data handling, such as using electronic data capture systems, randomizing and blinding the people and the researchers, doing quality checks and audits, and setting up data monitoring committees.

c)   Regulatory Compliance and Ethical Conduct:

There are different rules and ethical standards that try to ensure the respect, security, and well-being of the people involved in clinical trials, as well as the researchers and the funders. These rules and standards may differ depending on the country, region, or institution, and may evolve over time.

They must follow them or face legal, reputational, or trial-ending consequences. To prevent this, clinical trial management should know and follow the rules and ethics, such as getting approvals from the regulators and the ethics committees, reporting any bad outcomes or major violations, and getting informed consent and protecting the participants' privacy.

d)   Budget and Timeline: Clinical trials need a lot of money and time, and careful planning and management of the resources and activities in the trial. But sometimes, things like recruitment delays, participant dropouts, technical problems, or protocol changes can make the budget and timeline change, and impact the trial's outcome and success. To reduce this risk, clinical trial management should plan for reasonable and adaptable budgets and timelines, track and assess the trial's progress and outcomes, and make changes and backup plans as necessary.

e) Communication and collaboration: There are many different stakeholders in clinical trials, such as the sponsors, the investigators, the participants, the contract research organizations, the vendors, the regulators, and the public. It is important that these stakeholders communicate and work well together for the trial to run smoothly and effectively.

But factors like geographical distance, cultural differences, conflicting interests, or lack of trust can impair communication and collaboration. To avoid this risk, clinical trial management should create and sustain clear and consistent communication channels, roles, and responsibilities, promote a culture of openness and respect, and enable knowledge sharing and feedback. 

In conclusion, this article discusses the significant features of Clinical Trial Management i.e. Clinical Trial Protocol, Quality, Cost, Length, Challenges and possible solutions. This article intends to give comprehensive overview of clinical trial management; and help lay a foundational understanding to conduct and deliver accurate, effective and efficient clinical trial management for clinical professionals such as, clinical trial managers, clinical program/project managers, clinicians, or any pharmaceutical management professionals. 

References:

1. Bakhai A, Bhalla K, Chambers M, et al. Practical tips for working effectively as a clinical trial project manager. Br J Cardiol> 2010;17:211-214.

2. Chen H, Liu Y, Yang Z, et al. Risk assessment and management in clinical trials. Drug Discovery Ther 2014;8:106-110.

3. Karanicolas PJ, Bhandari M. Maintaining relevance in randomized controlled trials: a pragmatic approach. J Bone Joint Surg Am 2009;91(Suppl 3):69-75.

4. Luce BR, Kramer JM, Goodman SN, et al. Rethinking randomized clinical trials for comparative effectiveness research: the need for transformational change. Ann Intern Med 2009;151:206-209.

5. Clinical Trials: A Practical Guide to Design, Analysis, and Reporting by Duolao Wang and Ameet Bakhai (2006)

6. Clinical Trial Management: A Guide to Success by Steven A. Zuckerman and Brent D. Manning (2018)

7. Project Management for Clinical Trials: A Practical Guide by Steven M. Glazer and Christopher A. Sinkule (2020)

8. The Clinical Trial Manager's Handbook: A Comprehensive Guide by Linda A. Grady (2020)

9. Clinical Trial Management: Concepts and Tools by Lisa Plitnick and Susan A. Lisko (2021)

10. The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines on Good Clinical Practice (GCP), which provide standards and principles for conducting and managing clinical trials.

11. The National Institutes of Health (NIH) Clinical Research Toolkit, which provides resources and tools for planning, conducting, and managing clinical trials.

12. The Project Management Institute (PMI) guide to project management body of knowledge (PMBOK), which provides best practices and processes for managing projects, including clinical trials.