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

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Conducting clinical trials at sites in the U.S. or Europe is costly, making every aspect of a trial more expensive. The financial costs add up quickly when you consider patient recruitment, staff training, and facility management. With drug development costs exceeding $2.6 billion per year, a cost-effective trial is vital for future innovation.

Although many factors affect your clinical trial’s success and overall cost, the location may have the biggest impact; followed by the expertise of the contract research organization (CRO) you select. India offers high quality clinical trials with lower associated costs, which is why so many biotech and pharma companies are looking to India for future clinical trials.

Healthcare infrastructure in India

The Indian government has instituted several programs to improve its healthcare system. Initiatives such as the National Health Mission make medical equipment and supplies more available and encourage community engagement. Other programs include massive upgrades to its digital infrastructure:

• Ayushman Bharat Digital Mission is creating “a national digital health ecosystem that supports universal health coverage.” This initiative provides various infrastructure and data services that help ensure the privacy of health-related personal information.
• eSanjeevani provides national primary healthcare telemedicine services. It is the largest documented system in the world.
• CoWIN app launched during the COVID-19 outbreak to roll out the COVID vaccine distribution and tracking system.
• ERaktKosh is a centralized blood bank management system. It has helped automate some of the regional blood banks and provides donor management solutions, blood grouping and screening, and tracking blood stock.

As India’s healthcare investments strengthen the infrastructure, clinical research becomes possible in more regions. Their network of public and private healthcare is also expanding quickly, giving sponsors and CROs access to more trial sites. Most of the clinics and hospitals are closer to cities, while there are fewer trained medical professionals in rural areas. However, the investments have paid off. Indian people have more access to healthcare than ever, shown by a dramatic increase in life expectancy that rose from 47.7 in 1970 to 68.2 in 2024.

“Hospital chains and hospital networks are actually also clearly modernising. Seventy per cent of the patients are in private hospital networks. Private hospital networks are now diversifying into tier two, and tier three cities, into tertiary networks as well. That gives you broad-based access to patients. So this is all the things that are going on that makes India pretty attractive for clinical trials.”

— Badrhi Srinivasan, Head of Global Clinical Operations, Novartis

Disease prevalence in the Indian population

Communicable diseases like Dengue and drug-resistant tuberculosis strains are a constant challenge. However, polio is all but eliminated and the healthcare system has HIV under control. Although the increased life expectancy is proof of healthcare progress, the prevalence of non-communicable diseases is also increasing.

Chronic diseases affect more people each year, including in India. Conditions like diabetes and cardiovascular diseases are the most common. However, cancer and neurological disorders like dementia are also on the rise, marking a need for more treatment availability for these debilitating illnesses.

Conducting more clinical research trials in countries with reasonable regulations and cost-effective solutions makes sense. This is where India shines and sponsors can benefit.

Sponsors benefit from holding clinical trials in India

India offers several distinct benefits that help sponsors, including lower operating costs, wider patient access, and experienced investigators. The country’s lower cost of living affects all areas of life, including medicine and clinical research.

It means that everything connected to managing the trial—laboratories, management, trial sites—costs far less than what it would cost in a country like the United States. Sponsors are taking notice and as of 2020, the country was third in clinical trials, behind the U.S. and China.

Yet, India’s benefits extend beyond the cost savings and friendly regulatory environment—such as higher enrollment opportunities that prevent underpowered studies. India is the most populous country in the world, with 1.45 billion people.

This offers a diverse pool of potential study participants. Plus, those from rural areas may not have received treatment for the condition that your new drug treats. A factor that can give you a better, cleaner base line of its impact on patient lives and health.

Lower costs and a wider patient pool are reason enough to include India in your clinical trial. However, all that access is nothing without experienced investigators to lead your clinical trial, which India also offers.

However, due diligence is always key when you select a Principal Investigator (PI)—data from a 2024 study showed that many PIs in India have only conducted a few trials. Although this may be because of older regulations that limited the number of clinical trials PIs could simultaneously supervise—another recent change increased the limit.

Indian regulatory changes shorten clinical trial timelines and reduce red tape

Prior to 2019, India was one of the slowest countries for clinical trials because the regulations took far longer to navigate than in other countries. So even when a CRO or sponsor tried to include India from the beginning, most of the trial was already enrolled by the time they were ready.

In recent years, that has been changing. Speaking at the 18th Annual BioPharma & Healthcare Summit in Boston on April 25th 2024 organised by the USA India Chamber of Commerce Dr. Christopher Corsico, Global Head of Development, GSK, said “We have seen movement and the timelines actually have decreased by about 30 to 40 per cent. So for a pure pharma play, actually if you include India early strategically, you can get them on board and participate in that global trial which brings the back-end benefit. You don’t have to run a phase four study if you have a large enough subpopulation from India to contribute to your phase three data.”

Regulations instituted in 2019 greatly simplified the path to clinical research in India. Guidelines implemented by the Ministry of Health and Family Welfare (MoHFW) in New Drugs and Clinical Trials Rules (NDCT) helped. They made the approval process faster and more predictable.

2024 saw yet another set of updates that made more improvements. Further streamlining the process, these updates improved patient safety protocols and aligned with global standards and Good Clinical Practice (GCP) guidelines.

Also in 2024, the MoHFW added a definition for contract research organizations (CROs) like CliniRx. All CROs must register with the Central Licensing Authority before they conduct any clinical trials in India. It also emphasized ethical standards with better handling of severe adverse events and compensation for participants harmed by the treatment being tested.

India’s regulatory landscape continues to evolve, changing the way clinical trials are conducted. The most recent changes have been beneficial to biopharma companies and patient welfare.

Challenges exist, but India’s potential is limitless

India has a somewhat rocky history with clinical research, which gave rise to the perception that clinical trials were lower in quality and not always conducted ethically. However, that perception may have been wrong:

“It is an absolute misperception that quality was poor. Infrastructure stepped up. We are currently at Boehringer Ingelheim running a large phase three global programme, where India participates in obesity. We see pleasantly fast approval timelines for the clinical trial application.”

— Dr. Uli Broedl, Sr. VP & Head Global Clinical Development, Boehringer Ingelheim

Although there were a few high-profile cases where trials that caused patient harm, most clinical research conducted in India meets high standards. Additionally, India’s newer regulatory structure clarifies payments for people harmed by clinical research and priorities patient safety and education.

• There is a shortage of trained physicians, nurses, and technical healthcare professionals, especially in the more remote rural areas—something the National Health Mission working to alleviate.
• Standardizing data collection: some data are collected manually, while others are captured via different digital platforms.
• Data security concerns regarding using new technologies, especially in decentralized trials (DCTs), could be addressed with an increased focus on tightening security protocols.

Most of the digital security concerns are already being addressed with the Digital India Initiative. As India overcomes these challenges, the country will become a premier destination for clinical trials—known for superior quality, better budget control, and shorter timelines.

References:

Selvaraj S, Karan K A, Srivastava S, Bhan N, & Mukhopadhyay I. (2022). India health system review. New Delhi: World Health Organization, Regional Office for South-East Asia. https://apo.who.int/publications/i/item/india-health-system-review

Vennu, Vishal & Saini, Prem. (2020). India’s Clinical Trial Regulatory Changes, Indian Researcher?s Awareness of Recently Changed Regulations, and the Impact of the New Drugs and Clinical Trial Rules: A Review. Indian Journal of Pharmaceutical Sciences. 82. 726-740. 10.36468/pharmaceutical-sciences.702. https://www.researchgate.net/publication/348657614_India’s_Clinical_Trial_Regulatory_Changes_Indian_Researchers_Awareness_of_Recently_Changed_Regulations_and_the_Impact_of_the_New_Drugs_and_Clinical_Trial_Rules_A_Review

Kumar A. (2023). The Transformation of The Indian Healthcare System. Cureus, 15(5), e39079. https://doi.org/10.7759/cureus.39079

PTI. “India Becoming Attractive for Clinical Trials, Says Pharma Industry Leaders.” The Economic Times, Economic Times, 27 Apr. 2024, https://economictimes.indiatimes.com/industry/healthcare/biotech/pharmaceuticals/india-becoming-attractive-for-clinical-trials-says-pharma-industry-leaders/articleshow/109651758.cms

Jana, A., & Chattopadhyay, A. (2022). Prevalence and potential determinants of chronic disease among elderly in India: Rural-urban perspectives. PloS one, 17(3), e0264937. https://doi.org/10.1371/journal.pone.0264937

Prabhakaran, Dorairaj et al. (2018) The changing patterns of cardiovascular diseases and their risk factors in the states of India: the Global Burden of Disease Study 1990–2016. The Lancet Global Health, Volume 6, Issue 12, e1339 – e1351. https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(18)30407-8/fulltext

Dias, A., & Patel, V. (2009). Closing the treatment gap for dementia in India. Indian journal of psychiatry, 51 Suppl 1(Suppl1), S93–S97. https://pmc.ncbi.nlm.nih.gov/articles/PMC3038542/

Dhillon, Preet K et al. (2018) The burden of cancers and their variations across the states of India: the Global Burden of Disease Study 1990–2016. The Lancet Oncology, Volume 19, Issue 10, 1289 – 1306 https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30447-9/fulltext

Kshirsagar, N. A., Pahuja, M., Chatterjee, N. S., & Kamboj, V. P. (2023). Early phase clinical trials in India: Need & scope. The Indian journal of medical research, 158(1), 17–20. https://doi.org/10.4103/ijmr.ijmr_1688_22

Case, L. D., & Ambrosius, W. T. (2007). Power and sample size. Methods in molecular biology (Clifton, N.J.), 404, 377–408. https://doi.org/10.1007/978-1-59745-530-5_19

Understanding the New Drugs and Clinical Trials (Amendment) Rules, 2024. https://www.linkedin.com/pulse/understanding-new-drugs-clinical-trials-amendment-rules-nakrani-ddeaf/

Compensation for Victims of Clinical Trials: New Drug & Clinical Trial Rules 2019 covers clauses related to compensation in case of injury or death in clinical trial or bioavailability or bioequivalence study of new drug or investigational new drug. https://cdsa.thsti.in/clinical-trials-compensation/

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Working with the right PI can steer your trial to success, but selecting an inexperienced investigator can do just the opposite. Less experienced PIs sometimes face challenges with patient recruitment and retention, data quality, and regulatory compliance. Using a systematic approach, contract research organisations (CROs) like CliniRx identify and support PIs who consistently deliver superior trial outcomes.

Comprehensive PI assessment and performance verification

Identifying skilled PIs for your clinical trial requires strict evaluation methods and ongoing performance monitoring. Therefore, sponsors and other stakeholders must evaluate all potential PIs to verify their qualifications and experience. This includes analysing past trial completion rates, recruitment success, and reviewing their publication history in relevant therapeutic areas. Also critical is evaluating the site infrastructure, support staff, and their access to target demographics.

CROs play an important role in ensuring that the selected PI can meet the study’s goals. They leverage evaluation frameworks that include examining key metrics such as historical protocol adherence rates, documentation quality, and patient retention rates. Also important, continuous monitoring and regular assessments of key performance indicators like enrollment and retention tracking, data quality assessments, and site visits help ensure consistent performance.

Throughout the trial, you can enhance your PI’s performance by making sure they have access to a proactive support infrastructure with dedicated site management teams, protocol-specific training programs, and intervention protocols to respond quickly to issues as they emerge. A typical framework includes regular site process assessments, documentation reviews, and protocol compliance verification. In addition, sharing best practices across sites, implementing data-driven improvement initiatives, regular feedback, and customised development programs can further improve performance.

Why the PI is critical for success

The PI is the heart of a clinical trial and oversees all aspects of the trial. Everything from patient wellbeing to meeting scientific objectives and regulatory compliance falls under their domain. An PI will set realistic goals, ensure timely and budget-compliant study completion, and develop site-specific protocols for regulatory and protocol compliance. They are also responsible for staff oversight, training, and performance monitoring, while identifying areas for improvement.

Balancing all areas of a clinical trial requires constant attention and a blend of training, education, and leadership skills. They must make wise decisions on where to investing resources can save time and prevent budget overruns and patient attrition. For example, a PI may notice confusion among the staff. So, they schedule additional staff training to get everyone on the same page. That additional training can have other benefits, including improving patient recruitment and retention.

Then, if something does need to change, the PI makes sure it is properly documented.

Effective PIs can mitigate potential issues like:

• Recruitment isn’t going according to plan, so they adjusted strategies before the trial fell behind schedule.
• Inconsistent reporting patterns among staff members or odd gaps in documentation led them to invest in training to bridge the gap.
• Team dynamics that can impact quality, like burnout, can be prevented by allocating more resources for staffing.

Developing promising PIs to bridge skill gaps

Although CROs and sponsors often seek experienced PIs for clinical trials, some investigators show promise, despite their lack of experience. Identifying and nurturing is vital to future clinical research. Creating a stronger talent pool of qualified PIs will only improve research quality. CROs can play a pivotal role in future clinical research by supporting such investigators through initiatives such as:

• Comprehensive training programs that include focused training on Good Clinical Practice (GCP), protocol management, and regulatory compliance help build strong foundations.
• Mentorship programs that pair promising PIs with seasoned investigators can give them practical insights and experience in real-world settings.
• Incremental responsibility allows less experienced PIs to gain experience by co-leading smaller trials or pilot studies under supervision before they’re assigned to larger trials.
• Regular performance reviews that include actionable feedback and tailored improvement plans.

Investing in the development of investigators with promising futures would reduce the risks associated with inexperienced investigators and enhance the overall quality of clinical trials.

Spotting and addressing red flags

Sometimes, despite best efforts, something goes wrong in the PI’s work. While a proactive support network should flag most issues, being able to identify these warning signs early allows sponsors and other stakeholders to act before the trial’s integrity or patient safety is compromised.

• Patient safety and ethical concerns: Ethical misconduct, like failure to follow the established protocols or delaying reports of adverse events, directly endangers patients. It can also lead to lawsuits and penalties. However, another cost of ethical mismanagement in high-profile studies is that they undermine public trust in clinical research.
• Operational and data quality issues: One of the most obvious is low recruitment, which can leave the study without enough data to draw reliable conclusions. This problem often cascades into cost overruns and timeline delays. In addition, poor data quality and analysis can severely impact the potential benefits of a trial, while completely unusable results can be the result of ineffective management.
• Leadership and communication deficits: A lack of clear, consistent communication with sponsors, site staff, and study participants is a sign of deeper organisational problems. When a PI does not develop and maintain strong relationships with key stakeholders, confidence in the trial’s management erodes and can affect everything.

Building effective PI relationships

Successful relationships between investigators, sponsors, and CROs rely on clear communication, real-time escalation protocols, and regular performance updates. CROs can facilitate these partnerships and help ensure success by:

• Offering regulatory guidance and training programs
• Sharing best practices and performance improvement initiatives
• Providing dedicated site management teams and strategic resource allocation

Improving patient-focused outcomes

Clinical trials face an average dropout rate of about 30%, which makes a careful selection of eligible participants crucial. Skilled PIs play a vital role in recruiting eligible participants and building strong relationships with study teams and participants. They also ensure personalised care and clear communication to boost retention and data accuracy.

By taking a rapport-building approach, experienced PIs can achieve retention rates as high as 95%-100%, protecting the study’s integrity and outcomes.

Partner with the right PI for clinical trial success

Your clinical trial’s success depends on selecting the right PI, so look for PIs with a collaborative leadership style, proven experience, and expertise within their therapeutic area. By taking a systematic approach to PI identification, validation, and ongoing support, you can make sure they have the tools and guidance needed to deliver excellent results. When you partner with experienced investigators, you can maximise patient safety, data quality, and trial efficiency.

Take the next step

Ready to transform your clinical trial outcomes? Contact us today to learn how we can help you identify the right PI for your clinical trial.

References:

Poongothai, S., Anjana, R. M., Aarthy, R., Unnikrishnan, R., Narayan, K. M. V., Ali, M. K., Karkuzhali, K., & Mohan, V. (2023). Strategies for participant retention in long term clinical trials: A participant -centric approaches. Perspectives in clinical research, 14(1), 3–9. https://doi.org/10.4103/picr.picr_161_21

Alexander W. (2013). The uphill path to successful clinical trials: keeping patients enrolled. P & T : a peer-reviewed journal for formulary management, 38(4), 225–227.

Feehan, A. K., & Garcia-Diaz, J. (2020). Investigator Responsibilities in Clinical Research. Ochsner journal, 20(1), 44–49. https://doi.org/10.31486/toj.19.0085

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Currently, as many as half of the world’s population will experience a mental disorder by the time they are 75. This includes depression, schizophrenia, and neurodegenerative diseases like Parkinson’s and Alzheimer’s diseases. However, many other therapeutic areas are easier to target than many types of CNS disease.

In recent years, some companies have scaled back their central nervous system (CNS) programs because of development difficulties and high costs, while others are taking alternative approaches to overcoming barriers.

Yet, navigating these challenges in neuroscience clinical trials is possible by understanding and addressing them.

Neuroscience clinical trial challenges

A significant challenge to neuroscience clinical trials is the decrease of active drug versus placebo response, and how it affects trial outcomes. A natural phenomenon, it nevertheless interferes with researchers’ ability to measure the treatment’s effectiveness, and it makes it appear that the new treatment isn’t working, or it doesn’t show enough benefit to receive regulatory approval.

Additionally, although progress has been made recently, limited availability of validated biomarkers presents a challenge. Whereas in cancer studies or other physical diseases have obvious, measurable markers like tumors or blood markers, mental disorders, and neurodegenerative diseases are not always so clear. In their limited absence for specific indications or populations, researchers instead group patients according to their symptoms and use semi-subjective or patient-reported primary endpoints.

Compounding the difficulties, high development, and clinical trial cost coupled with difficulty finding accurate measures for success make developing treatments for mental disorders difficult to justify financially.

Training can mitigate the placebo response in clinical trials

Considering that the placebo response varies in clinical trials from 13 to 50% in antidepressant trials and 6 to 41% in schizophrenia trials, you can take steps to mitigate it to improve trial results. Since it might be largely driven by patient as well as medical care provider expectations, your priority becomes managing expectations, which begins with a well-designed patient education program during recruitment and onboarding. By helping patients understand their role in the trial and the importance of accurate symptom reporting, your clinical trials can obtain more accurate data.

The data support this idea. One study focused on placebo response mitigation with an all-placebo study of major depressive and psychotic disorders. The researchers were able to reduce the placebo effect by using a Placebo Control Reminder Script (PCRS), which provided education on placebo response.

In addition to patient education, proper and consistent psychometric assessments by selected raters is critical, making a robust training program necessary. Implementing training that follows agreed rating conventions that addresses the raters’ variabilities and potential drifts is fundamental to increasing the likelihood of success in neuroscience clinical studies.

Reduce attrition of neuroscience clinical trial study participants

Understanding why people leave studies is vital to keeping them enrolled—and completing your study. Of course, you cannot control all the reasons study participants drop out. Some leave because the treatment was not working for them, or because the treatment’s side effects were unacceptable.

However, leaving aside things that you cannot control, there are several things you can do to reduce attrition in your neuroscience clinical trial.

Simplify and streamline eligibility and trial compliance requirements

If your processes or protocols are overly complicated, you will only be able to keep the most dedicated patients, losing otherwise excellent candidates. Making the clinical trial experience as convenient for your patients as possible will help more study participants enroll and complete the trial. Here are a few ideas:

• Make it easier to determine eligibility with online forms, because everything you do to make it easier invites more potential participants.
• Use existing technology—like tablets and phones—to reduce paperwork and collect data instead of enormous packets. Patients can be intimidated when they have a stack of paperwork to complete for something that might help them.
• Reduce check-in difficulty and scheduling conflicts. Offer virtual office visits instead of in-person appointments where possible. Many study participants have busy schedules, and sticking to a strict schedule of clinical appointments is difficult, especially when you factor in travel time.
• Simplifying study visits by only including assessments that are mandatory to address the protocol hypothesis will also decrease the study subject burden but also increase sites’ acceptance of the new study.

Improve patient education and engagement

Communication prevents questions from becoming problems. Your study participants need clear communication that shows how either they or future patients will benefit from the research. In addition, the stigma connected to mental disorders does not help patient recruitment or retention. By making study participants feel part of something greater, they are more likely to stay enrolled—even if the protocols are a little burdensome. Here are a few more ways to improve education and keep your patients engaged in the process:

• Use plain language in marketing materials and clinical literature. Make the material easy to understand, even if the topic is complex.
• Make a two-way communication part of the study process. Engage your patients by sharing tips to help them manage their condition, information about the study progress, and other information that keeps them engaged.
• Make online support groups available. Allow patients to reach out anonymously for advice and help.
• When patients drop out, ask them why. Get feedback on what made them leave the trial early and what might change their mind.
• Consider involving patient associations in selected indications from the early days when the study is designed and solicit their input to the planned study participant path.

Reduce the operational burden on study sites

As neuroscience trial protocols become more complex, some study sites might struggle to meet requirements. Those sites are sometimes under-staffed with budget concerns and other operational hurdles like technology limitations or lack of experience with clinical trials.

CROs like CliniRx can help manage challenges and mitigate the operational burden by providing support through their network of qualified vendors. Reducing the overall operational burden means more sites can take part, which gives you easier access to qualified study participants.

Reduce the operational burden with these ideas:

• Use clear communication methods to keep everyone informed.
• Provide sites with effective pre-screening support and training. Preparing sites ahead of the trial can reduce hiccups in procedures and increase protocol compliance.
• Ensure clarity and specificity in your protocol’s schedule of activities and any amendments.
• Reduce the onboarding burden by making sure that technology you require sites to use has thorough online learning resources.
• Invest into strategic relationships with sites rather than transactional only. This will allow sites to plan in advance for potential new studies ahead of time and increase sites’ availability for your new project.

Improve neuroscience trials patient selection criteria

For all our scientific advancements, our understanding of the pathophysiology behind mental disorders is still limited, and for up to 60% of patients response to treatment can be suboptimal, insignificant or none.

With few known biological markers, trial protocols depend heavily on patient-reported outcomes.

However, there are things you can develop to improve the patient selection criteria for your next neuroscience clinical trial:

• Patient education programs to help collect more accurate information.
• Strategies to select more homogeneous yet diverse groups for trials.
• Develop and validate translational biomarkers for pharmacodynamic assessments and patient selection.

Improve future neuroscience trial outcomes by addressing current challenges

To successfully complete clinical neuroscience trials, your team will have to take a multifaceted approach. While the placebo response rates, limited biomarkers, and operational difficulties are hurdles, strategic solutions can improve the outcomes.

By adopting enhanced patient education programs, streamlining procedures, and improving site support, sponsors, and CROs can work together to improve data quality and minimise patient attrition and placebo response.

References:

Age of onset and cumulative risk of mental disorders: a cross-national analysis of population surveys from 29 countries. McGrath, John JAguilar-Gaxiola, Sergio et al. The Lancet Psychiatry, Volume 10, Issue 9, 668 – 681

Gribkoff, V. K., & Kaczmarek, L. K. (2017). The need for new approaches in CNS drug discovery: Why drugs have failed, and what can be done to improve outcomes. Neuropharmacology, 120, 11–19. https://doi.org/10.1016/j.neuropharm.2016.03.021

Holper L. (2020). Raising Placebo Efficacy in Antidepressant Trials Across Decades Explained by Small-Study Effects: A Meta-Reanalysis. Frontiers in psychiatry, 11, 633. https://doi.org/10.3389/fpsyt.2020.00633

Rief, W., Nestoriuc, Y., Weiss, S., Welzel, E., Barsky, A. J., & Hofmann, S. G. (2009). Meta-analysis of the placebo response in antidepressant trials. Journal of affective disorders, 118(1-3), 1–8. https://doi.org/10.1016/j.jad.2009.01.029

Kinon, B. J., Potts, A. J., & Watson, S. B. (2011). Placebo response in clinical trials with schizophrenia patients. Current opinion in psychiatry, 24(2), 107–113. https://doi.org/10.1097/YCO.0b013e32834381b0

Cohen, E.A., Hassman, H.H., Ereshefsky, L. et al. Placebo response mitigation with a participant-focused psychoeducational procedure: a randomized, single-blind, all placebo study in major depressive and psychotic disorders. Neuropsychopharmacol. 46, 844–850 (2021). https://doi.org/10.1038/s41386-020-00911-5

Howes, O.D., Thase, M.E. & Pillinger, T. Treatment resistance in psychiatry: state of the art and new directions. Mol Psychiatry 27, 58–72 (2022). https://doi.org/10.1038/s41380-021-01200-3

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International Regulatory Harmonization

One significant multinational trial trend is the push for regulatory harmonization. Different countries (with their varying regulatory requirements) can complicate the process of conducting trials across borders. Efforts geared toward aligning these regulations to streamline the approval process/ensure trial consistency include initiatives such as the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH): bringing together regulatory authorities/industry experts as they look to flesh out global drug development guidelines. Progress has been made, but challenges are still there—particularly in regions with evolving regulatory frameworks.

Enhancing Patient Diversity

Patient diversity is also part and parcel of multinational trials. A diverse patient population, after all, can boost the ability to generalize trial results and ensure effective therapies no matter the demographics at hand. Challenges do arise when it comes to recruitment/retention, however, as cultural differences, language barriers, and unique healthcare systems can all impact participation. It is therefore extremely important to adopt a multi-pronged approach ranging from engaging local healthcare providers, to tailoring recruitment materials per cultural differences, and launching community outreach programs to ensure representation from diverse populations.

The COVID-19 Impact

COVID-19 pandemic and the after effects profoundly impacted multinational clinical trials, meanwhile, highlighting the need for adaptability/resilience after lockdowns, travel restrictions, and overwhelmed healthcare systems disrupted trial operations: breeding delays and protocol modifications. Virtual trial visits, remote monitoring, and decentralized trial models—adaptations showing promise as a means to improve trial efficiency and patient convenience—eventually emerged as solutions to carry on with research while still ensuring patient safety. They do present their very own challenges, however, as it relates to digital literacy, data security, and regulatory considerations for virtual trials.

Conclusion

Conducting clinical trials at a multinational level is chock-full of both opportunities and challenges. Efforts geared toward regulatory harmonization seek to add efficiency to trial processes, while patient diversity must be prioritized to enhance the relevancy of results. The COVID-19 pandemic specifically highlighted just how important flexibility/innovation are in trial operations, and as these efforts continue to forge on, collaboration among regulators, researchers, and patient communities is nothing short of crucial to address related challenges and improve health outcomes via clinical research on a global scale.

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Enhanced Data Collection

Data collection stands as one of the most significant digital health technology impacts in clinical trials. As one example, wearable devices can continuously monitor vital signs, activity levels, and other physiological parameters. This real-time data stream gives researchers a more detailed view of a patient’s health status than what would be possible otherwise via periodic clinic visits. Mobile apps, meanwhile, give patients the ability to report symptoms, better adhere to medication regimens, and account for lifestyle factors quite easily from their smartphones. The corresponding result? A mountain of objective/subjective data that can improve the ability to understand a drug’s efficacy and safety profile.

Empowering Patient Engagement

Patient engagement is yet one more area greatly influenced by digital health tools, with clinical trials zeroing in on the patients themselves to a greater degree and becoming more accessible with help from wearables and mobile apps. While the former tool empowers patients to actively participate in their care (promoting self-monitoring and an improved awareness of their health), the latter provides a way for patients to easily communicate with researchers, receive appointment/medication reminders, and access educational materials. All in all, this increased engagement can boost trial retention rates and help better understand patient experiences with investigational treatment.

Navigating Regulatory Considerations

Nevertheless, weaving these technologies into clinical trials also presents a variety of considerations from a regulatory standpoint. Data security/privacy are of course highly important, especially given the sensitivity surrounding health information collected via wearables/mobile apps. It’s crucial to comply with related regulations such as HIPAA (Health Insurance Portability and Accountability Act) to protect patient data, and the FDA (Food and Drug Administration) and other regulatory bodies are in the process of developing guidelines to make sure data collected through digital health technologies is both valid and reliable; researchers must adhere to the same to ensure trial results integrity.

Conclusion: Embracing the Future of Clinical Trials

The inclusion of wearables and mobile apps within clinical trials is taking data collection and patient engagement to brand-new heights—with these technologies offering a wealth of both objective and subjective data to provide a more holistic understanding of patient health. Researchers must of course navigate regulatory considerations to ensure data security/validity, however, and as digital health continues to evolve, its role in clinical trials will only get bigger to see fresh opportunities for improved research outcomes and patient care.

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Patient Recruitment, A Hurdle

First and foremost, patient recruitment is an overwhelming challenge; it’s difficult to find eligible participants as small patient populations are scattered across different regions. Traditional recruitment methods can be ineffective in this case—delaying trial initiation/completion—and instead call for newfound approaches (e.g., global collaborations and patient registries) that give researchers access to a larger pool of potential participants in addition to streamlined recruiting. Patient advocacy groups also play a large role in raising awareness and connecting patients with ongoing trials.

Tailored Solutions, Innovative Trial Designs

To help address the unique aspects of rare diseases, meanwhile, trials must feature an innovative design. As one example of this, adaptive trials that allow for protocol modifications based on interim data add an element of flexibility; this is particularly beneficial for diseases with variable progression rates or unpredictable responses to treatment. Basket/umbrella trials are other innovative designs that give researchers the ability to study multiple therapies or patient subgroups simultaneously—maximizing both efficiency and resources.

Orphan Drug Act, Incentivizing Drug Development

Notably, Regulatory agencies have recognized the aforementioned challenges in rare disease research and in turn provide incentives to encourage the development of treatments. Orphan Drug Designation, for example, offers financial incentives and market exclusivity to companies who make it their work to develop therapies for rare diseases. Fast-track designation and priority review processes, meanwhile, speed up regulatory reviews for promising treatments and thus cut down the time it takes to go to market.

These advancements aside, clinical trials for rare diseases are still considered complex with regulatory requirements to navigate and costs to overcome. It’s also necessary to ensure trial endpoints are meaningful/relevant to patients in demonstrating treatment effectiveness.

Collaborative Efforts, The Path Forward

Innovations in trial design, patient recruitment strategies, and regulatory incentives can all bring progress to rare disease research that is still considered challenging overall. Researchers, patient communities, and regulatory stakeholders must therefore team up to move past barriers in search of necessary treatments; as these efforts continue to unfold over time, improved outcomes and a brighter future for patients remain in sight.

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