Rescue study become necessary when a clinical trial encounters challenges that prevent it from gathering high-quality data. Problems like resource shortages, questionable data, recruitment issues, or missing deadlines can result in significant delays and cost overruns, putting the trial’s success at risk. A rescue study’s purpose is to restore the trial’s integrity and reliability, leading it to a successful outcome.
Over 80% of trials fail to finish on time, and 20% of those are delayed by at least six months. Additionally, up to 50% of all sites may only enroll one or fewer patients. With statistics like that, it’s no surprise that at least a few trials convert to rescue trials.
Fortunately, early intervention can save a trial from complete derailment—saving money, time, and valuable data. If the team addresses problems early enough, it may never need a rescue phase. However, if a trial is floundering, the rescue process includes reviewing the trial design, assessing the problems, and developing a rescue plan. Whether the trial’s plan needs revision or patient recruitment is lagging, the goal is to protect the investment and ensure reliable results.
Warning Signs: Does your trial need rescue?
No matter how meticulously your team planned the trial, some things are unpredictable. Regardless, red flags that indicate your trial needs help include:
- Never-ending patient enrollment / retention challenges: if you aren’t struggling to enroll patients, you’re fighting to keep them from dropping out.
- Data quality seems suspect: things aren’t adding up the way they should, or you’re missing key data that puts the endpoints at risk.
- Protocol deviations are expected but too many may be a warning sign.
- Budget and timeline overruns are impacting the study, making it impossible to predict the final deliverable timing.
- Staffing or other resource shortages result in missed data collection or incomplete patient follow-up.
- Regulatory compliance issues that lead to delayed or incomplete submissions.
What went wrong? Common causes of clinical trial setbacks
Clinical trials require careful planning and preparation to ensure a successful project. Many setbacks are preventable, but some can catch you off-guard:
Poor study design
Failure to design a study with enough of a cushion for unexpected challenges is one problem. However, design problems can include many issues, such as poorly described techniques, vague study endpoints, and inappropriate control groups.
Strained CRO-sponsor relationship
Maybe the communication was off, or it was a mismatch between the sponsor and CRO, but sometimes the relationship becomes too strained to continue the journey together.
Resource shortages
Resource constraints can include anything from financial limitations to staff shortages, drug supply problems and more.
Operational inefficiencies
These typically stem from a lack of planning or preparation, but can also be reflective of inadequate staff training, an inexperienced Principal Investigator, or a poor site selection.
Communication breakdowns
True, communication is a two-way process that requires mutual understanding where the participants share information, news, ideas, and feelings—but also creating and sharing meaning. Clinical trials without transparent communication falter and, if it isn’t corrected quickly, fail.
Regulatory delays
Regulatory landscape is complex and changes from country to country. One missing detail from your submission and the entire thing can be delayed.
Patient recruitment & retention
Without study participants, there is no clinical study. Even though recruitment and retention are difficult for many trials, patient participation is necessary to obtain critical data for a final report.
Evaluate the clinical trial for rescue
Before taking any action, you must evaluate the trial’s current situation. Discover where it went wrong and how to get it back on track. The goal of a rescue trial is to get your study back on a path to success with as little disruption as possible. An effective rescue plan needs accurate information, so evaluating the clinical trial rescue will include at least the following:
- Comprehensive gap analysis
- Stakeholder analysis and interviews
- Performance metrics evaluation
- Root cause analysis
- Risk assessment
- Identify and prioritize critical issues
- Identify rate limiting factors
Developing a rescue strategy
A clinical trial rescue needs a solid plan with realistic goals, which is especially important because the study may have already gone over budget and missed critical deadlines. Taking the information gained from your evaluation, begin creating a rescue strategy to get the trial back on track.
Here are a few factors to consider:
- Resource allocation: From staff to budget and technology, you’ll need to reallocate resources to adequately plan your rescue strategy.
- Timeline adjustments: If your trial has already missed deadlines, this item is likely at the top of your list. When you adjust timelines, make sure you include the time it will take to implement the rescue plan and complete the study.
- Budget recalibration: Clinical trials are notorious for going over budget. Recalibrating your budget with the adjusted amounts from the rescue trial plan will help ensure you finish strong.
Additional regulatory challenges
Regulatory issues can make even the best trial designs stall. However, once a trial needs rescue, expect more regulatory challenges. They typically appear in several areas:
- Protocol amendments: rescue trials often require extensive changes to the original trial protocol, followed by a thorough review and approval process by regulatory bodies.
- Data integrity: ensuring the data’s accuracy and integrity is vital—both before and after rescue. Regulators closely monitor the data and assess its validity, especially if there were significant modifications.
- Informed consent: trials that undergo a rescue phase often include changes that affect the participants requiring updated informed consent. This likely includes Ethics/IRB reviews and approvals, ensuring the patients’ safety and rights are protected.
- Engage with regulatory authorities, if necessary, to discuss the challenges the trial faces and get their input.
- In the case of multiple regulatory authorities: As each region has its own unique set of requirements, enlisting the help of a specialist can help keep the trial in compliance in all regions.
Successfully navigating the regulatory challenges associated with a rescue trial requires effective communication, extensive regulatory knowledge, and thorough planning and documentation—from beginning to end.
Additional considerations
Clinical trial rescue isn’t a one-person operation. You need management’s approval and internal support from the team. Working with them to solve the problem is the only way to come out the other side with reliable data. You’ll also have to identify and mend affected relationships, whether between vendors, sponsor staff, internal team members and/or management.
Whether it was a sponsor who didn’t listen when a project manager raised concerns or staff members who didn’t really understand their responsibilities—often, many failures begin with a lack of communication. So, any rescue plan must have a clear, robust communication plan.
Other considerations may include:
- Site management optimization
- Data cleanup and management improvements
- Accelerating recruitment strategies
- Enhanced monitoring approaches
- Technology implementation and updates.
- Staff training and development.
- Phased approach to changes
- Enhanced tracking and measuring.
- Managing stakeholder expectations
Help your CRO succeed
If you’ve decided to work with a contract research organization (CRO) like CliniRx, give them everything they need to be successful. Supply them with all the information they need in as detailed a format as possible. The more information you give them, the clearer picture they’ll have of your trial—and be better able to chart a course out of danger and into success.
Information should include:
- Complete list and details of all sites, locations, and IRB/ethics approvals status
- Progress updates that include site setup and contract details
- Information on any new sites being considered
- Status of grant payments, with all detail included
- Detailed reports on site and patient monitoring, including data gathered
- Summary of patient engagement strategies
- Details of any legal representation
- Insurance policy status and ownership information
Case Studies: Successful Rescues
CliniRx has extensive experience successfully migrating and completing rescue trials. Whether your trial is facing enrollment challenges, resource shortages, or operational problems, we can help.
Tuberous Sclerosis Complex
This Phase IIB clinical study included children, adolescents and adults aged 5 to 30 years who have seizures associated with Tuberous Sclerosis Complex (TSC), struggled with enrollment. It was a multi-centric, 30-week study followed by a 1-year open label extension.
The study planned to enroll approximately 54 patients with TSC from 30 sites spread across 8 countries in the United States, Europe, and India. Globally, the first site was activated in December 2021 and the first patient was screened in March 2022. Despite initiating the study almost a year and a half later in India. We were able to enroll 25% of the eligible patients for the study within a year.
The first patient in India was screened in August 2023 and screening of 17 and enrollment of 15 of these screened subjects were completed by August 2024. Of all the participating countries, India remained the highest recruiting country by the time enrollment was completed.
Rare Disease
A Phase II clinical study of a drug-device combination product in Rare Disease involving pediatric patients, presented recruitment challenges even for the Lead CRO. CliniRx strategically selected key sites from our database and adopted a multi-pronged approach. We engaged with various patient groups and actively participated in local events organized by them, ultimately contributing to closing enrollment within timelines.
Building resilience for future trials
While rescue trials are sometimes necessary, preventing them is possible in many cases. Including a contingency plan with early warning systems that specify actions to take when something isn’t progressing as planned, staff training, and vendor management strategies all contribute to a study’s potential success. Additionally, using an adaptive trial design may help build resilience into the trial before anything goes wrong.
By carefully considering all challenges a trial can face and building contingency plans into the protocol, you can keep it on track, headed for successful completion.
Key takeaways
Although challenging, clinical trial rescue is an opportunity to salvage success from a potential failure. Successful rescues show that communication, early recognition of warning signs, and a systematic problem-solving approach can revive struggling trial—protecting valuable investments.
Far beyond saving a single research study, a successful trial rescue often finishes stronger with better data that contributes to knowledge that helps prevent similar challenges in the future.
As clinical trials become more complex, incorporating adaptive designs, remote monitoring, and diverse data sources, identifying and addressing issues quickly also becomes more critical. The evolution of trial management technologies, combined with lessons learned from previous work, provides teams with better tools and strategies to handle trial challenges and possibly prevent them from derailing future trials.
The true cost of a trial failure is more than financial. It represents missed opportunities to help patients and setbacks in medical advancement. Trial rescue enables research organizations to better facilitate the advancement of medical science and improving patient care.
Whether your trial is currently facing challenges, or you are planning future research, building resilience into your processes and maintaining open communication channels with all stakeholders will help you spot early warning signs. Through planning and monitoring with rapid interventions as needed, your team can get your clinical trial back on the path toward success.
Our experts at CliniRx can help you get your trial back on track—reach out to find out how we can help.
References
Imam, A., Wariri, O., Dibbasey, T., Camara, A., Mendy, A., Sanyang, A. N., Ceesay, M., Jallow, S., Jallow, A. E., Bah, K., Johnson, N., Trawally, E., Sowe, D., Darboe, A., Kampmann, B., & Idoko, O. T. (2021). Conducting clinical research in a resource-constrained setting: lessons from a longitudinal cohort study in The Gambia. BMJ global health, 6(8), e006419. https://doi.org/10.1136/bmjgh-2021-006419
Francis, G., & O’Kane, M. (2020, November 11). Building resilience into clinical trial design and conduct during the pandemic. MHRA Inspectorate. https://mhrainspectorate.blog.gov.uk/2020/11/11/building-resilience-into-clinical-trial-design-and-conduct-during-the-pandemic/
Fogel D. B. (2018). Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: A review. Contemporary clinical trials communications, 11, 156–164. https://doi.org/10.1016/j.conctc.2018.08.001