Backup Plans in Clinical Trials: A Focus on Rheumatology

Table of Contents

1. Common Types of Backup Plans in Rheumatology Clinical Trials 
2. Adapting to Evolving Therapies in Rheumatology Trials
3. Backup Countries
4. Protocol Amendments: A Proactive Strategy 
5. Positive Impact of Backup Sites on the Conduct of the Study
6. Financial Impact of Backup Sites 

Rheumatology clinical trials, by their very nature, are unpredictable. Unforeseen complications can arise, threatening the continuity of the trial. This unpredictability underscores the necessity of backup plans. These plans can mitigate risks and ensure the trial’s continuity. The investment level for a proper backup plan is crucial as the potential loss from missed timelines, missed market positioning, prolonged studies, and even potential study failure can be substantial. While the cost of a backup plan is not necessarily large compared to the total value of the project, this aspect is frequently overlooked in planning.

Common Types of Backup Plans in Rheumatology Clinical Trials 

In rheumatology clinical trials, common types of backup plans include backup sites and protocol amendments triggered by certain setbacks. Backup sites are a significant part of this strategy.  

Backup site selection involves costs, as investigators expect compensation for being a second choice in a given trial. This is not a significant amount—a price that reflects the effort required on their part. The relationship with these sites is paramount in maintaining a good rapport, especially when a site is being considered as a “plan B.”  

It is also important to differentiate between backup sites in existing countries and backup countries. If the chosen country faces delays or proves to be an unsuitable choice due to various potential factors, having backup sites will only provide limited mitigation. Therefore, while planning for backup sites, the potential delay or unsuitability of an entire country should also be considered.  

Adapting to Evolving Therapies in Rheumatology Trials

In recent years, rheumatology patients have increasingly been prescribed biologic treatments, targeted synthetics, and Janus Kinase (JAK) inhibitors due to the availability of numerous new drugs. Current studies aim to identify and enroll patients who are still on methotrexate. However, the pool of these patients has decreased as most have transitioned to biologic treatments. Therefore, constantly adapting to the evolving therapeutic landscape is crucial to the successful completion of rheumatology trials. 

Backup Countries  

The need for backup countries has become increasingly vital. A typical rheumatoid arthritis study often begins by targeting patients who have not responded to methotrexate, followed by those who have failed biologics, and then JAK inhibitors. The complexity arises from the coverage provided by local health insurance. It is not uncommon for insurance policies to shift and begin covering biologic treatments even within the same study lifecycle. For instance, a study may initially focus on a patient population comprising 40% biologic failures and 60% methotrexate failures. However, sponsors may later decide to aim to an equal split between the two groups, necessitating the need for a backup country. As finding such countries becomes increasingly challenging, the importance of having backup plans is underscored.  

An emerging challenge is that, given the increasing number of studies and approved therapies, the focus has shifted towards achieving low disease activity. This heightened goal significantly influences the design of these studies.  

Protocol Amendments: A Proactive Strategy  

Protocol amendments triggered by certain milestones serve as a proactive strategy to manage potential delays. This approach involves planning in advance for alternative scenarios. For instance, if by a predetermined date, the patient recruitment is significantly below projections, it may be necessary to consider a change in the rheumatology patient population. This could be particularly relevant if the original patient population proves too challenging to find. While this strategy may not traditionally fall under the category of a “backup plan,” it is a crucial part of effective trial management. By anticipating potential roadblocks and having a plan in place to navigate them, researchers can ensure the continuity of the trial, thereby minimizing disruptions and maintaining the integrity of the study. This forward-thinking approach underscores the importance of flexibility and adaptability in the conduct of clinical trials. 

Positive Impact of Backup Sites on the Conduct of the Study 

Backup sites play a pivotal role in the successful conduct of a rheumatology study, offering an insurance However, the efficacy of backup sites does not solely depend on a contingency plan in place. It also hinges on maintaining a good relationship with these sites. This involves regular communication, acknowledging their importance in the overall trial process, and ensuring they feel valued and integral to the study. This positive relationship can enhance the overall conduct of the study, contributing to its success. 

Financial Impact of Backup Sites 

Incorporating backup sites into a project involves financial considerations that need to be meticulously evaluated. While the initial costs of formulating and executing these plans can be significant, they do not constitute a substantial portion of the overall project cost. This includes the processes of identifying, approving, and establishing backup sites or even entire countries.  

To put this into perspective, backup sites would typically cost a very small percentage of the budget, a relatively small amount compared to the whole study. This cost estimate, of course, varies depending on the size of the project. Despite this expense, the impact it can have on the risk management of the study makes it a worthwhile investment. The cost represents the approval and site selection, which are crucial steps in ensuring the project’s success. Therefore, the integration of backup sites is a strategic move in risk management, providing a safety net that far outweighs the initial financial outlay.  

The cost associated with contingency planning should be weighed against the potential financial consequences of a trial stumbling due to insufficient preparation. For instance, a scenario where a drug is ready for market launch. If there are complications in clinical trials that result in a delay of the launch by even a month, it could lead to substantial financial consequences.  

Key considerations such as planning, shipment, and the risk of a Principal Investigator (PI) falling ill must be factored in. Thus, the financial safeguard provided by backup plans can justify their cost.   

In conclusion, backup plans in rheumatology are not merely an optional extra, but a necessity. They represent a strategic investment that can mitigate risks, ensure trial continuity, and ultimately contribute to the success of the study. As we move forward, it is crucial to continue refining these plans, learning from case studies, and exploring new strategies to further optimize their implementation and impact in rheumatology clinical trials. This forward-thinking approach will be key to navigating the complexities and challenges of clinical trials in the future. 

About the Author 

Pavle Vukojevic, MD, M.Sc., 

Dr. Vukojevic has over 25 years’ experience in clinical development within the CRO industry and over 10 years of clinical/academic practice in rheumatology. He is an experienced clinical development executive at global level with extensive knowledge of international drug development processes and procedures (phases I-IV). He is the author of “Conducting Clinical Trials in Europe: An Insider’s Analysis” expert report (edition Insight Pharma Reports for the Cambridge Healthtech Institute).

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