How to De-Risk Clinical Trials in Today’s Complex Environment

May 29, 2023

As published in Pharmaceutical Outsourcing

By Robert Hummel, Chief Operating Officer

Halfway through 2023, the clinical trials space has never been more exciting, and turbulent. There have been some incredible breakthroughs, such as the success of Enhertu, an experimental drug used in a clinical trial sponsored by Daiichi Sankyo and Astra Zeneca, that extended the life of metastatic breast cancer patients by six months. At the same time, we have seen a lot written about biotech companies cutting staff, conserving cash, and thinning their drug development pipelines. Add the failure of Silicon Valley Bank— which was an active player in biotech investing and funding—and suddenly, life sciences companies are finding themselves more strained than ever.

As the biopharmaceutical industry continues to face extraordinary challenges, it is becoming increasingly important for companies to identify strategic ways to balance managing financial risks with testing drugs that have the greatest potential for health impact. With this in mind, we need to better understand why the clinical trials landscape is becoming increasingly volatile, and what effect that may have in the future.

2023: The Year of De-Risking Clinical Trials

According to the Tufts Center for the Study of Drug Development, it takes more than $2.6 billion and well over a decade to bring a new prescription drug to the market. In the current economic climate, there is a marked tightening of capital and investment dollars. Now, more than ever, smaller biopharmaceutical companies are struggling to raise capital, as an IQVIA report highlighted a 39% decrease in biopharma investments in 2022 alone. As a result, sponsors are taking fewer risks in clinical trials, opting instead for therapeutic areas and drug classes with the highest potential to make it to market and the patients who need them most.

While the R&D pipeline growth has been gradually slowing over the last two years, we’re just now seeing the numbers. In 2022, the U.S. Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) approved 37 new drug therapies, the lowest number of novel drugs approved since 2016. Many of CDER’s approvals in 2022 were gene therapies to treat or cure rare diseases – a high[1]ROI therapeutic field after the passage of the Orphan Drug Act in 1983. But with the rising costs of drug development and increasing competition, the numbers of rare disease trials are again growing as sponsors reprioritize portfolios to focus resources on the strongest trials with greater potential returns. Amgen’s $26.4 billion acquisition of rare disease biopharma company Horizon Therapeutics is a sign of this shift towards de-risking the outcomes of trial investments.

While emphasizing drugs that have strong potential financial returns and health impact is one way for sponsors to increase chances of success with the studies they invest in, they still must navigate complexities surrounding study operations. Recruitment and patient centricity remain big challenges for sponsors – with enrollment being a critical issue that contributes significantly to the failure, delay, or discontinuation of trials, especially in randomized clinical trials (RCTs). Additionally, preparation is another pressing issue for clinical trial teams. Our understanding is that because of the pressure to get trials moving, especially felt by CROs (Contract Research Organization), there is a much higher frequency of study teams that just aren’t fully prepared. Historically, about 20% of trials Suvoda supported experienced sponsor-driven delays. Starting in 2021, it was closer to 35-40%, and in 2022, it jumped to 60%.

This pressure to get started and show impact will have an almost counterintuitive effect – increasing the likelihood that trials are initiated before all the details have been worked through, which trickles down to more uncertainty, change, and amendments during a trial. All of which adds to the cost of the study.

Flexibility and Adaptability in Study Design

In this era of vigorous financial risk mitigation, there needs to be additional focus on delivering with high quality and making sure timelines are staying on track. Innovative, purpose-built, eClinical technology solutions can help deliver that coveted level of quality and enable companies to build necessary adaptability into their studies to help mitigate risk. For example, integrating an IRT (Interactive Response Technology) system with the Bayesian Futility Analysis algorithm can help sponsors efficiently assign patients to a trial cohort based on the therapy’s probability of success. This allows sponsors to quickly drop underperforming treatments and refocus resources on the most effective therapies. Results are available much faster than with traditional trial designs, thereby reducing costs while still producing high-quality data. This approach helps sponsors get more value from their clinical trials without sacrificing accuracy or quality.

Free-picking functionality within an IRT system is another practical tool to help sponsors improve efficiency and reduce supply risk within their trials. Free-picking provides large biotech and pharmaceutical companies more flexibility and control over the supply chain by streamlining the order processing times and enabling the sharing of supplies across multiple studies. Free-picking also supports strategies such as Just-in-Time (JIT) labeling, which provides greater flexibility in the supply chain. It also enables sponsors to better manage inventory levels while meeting patient needs throughout a study.

Incorporating forecasting tools that are integrated with IRT is also proving to help small and large biotech and pharmaceutical companies gain efficiencies and adapt more quickly to change throughout a trial. By moving away from legacy tools, like spreadsheets, in favor of solutions that provide real-time updates, study teams can improve visibility across the supply chain and adjust drug distributions more readily. When seamlessly integrated with IRT, drug supply can adjust quickly based on up-to-date patient data to reduce drug wastage or shortages.

The Pragmatic Approach With Technology

Although technology can undoubtedly help simplify processes and mitigate risks in clinical trials, too much of it can lead to more problems rather than solutions – making studies more complicated than they should be. This means that sponsors must not just look at what’s flashy and cool, but also pay attention to what’s proven and practical and solves today’s challenges, while still anticipating trials of the future.

Instead of focusing on the latest technology, sponsors can approach clinical trials with an eye toward patient-centricity. At the end of the day, clinical trials are experiments with real people. So, when sponsors, study managers, clinicians, technicians, and all other associated parties take the scientist hat off, it can be easier to see what they really need to make patient recruitment and the patient experience better. This practical approach looks at the patient's experience and asks questions: How can I make it better? How can I remove friction? How can I make the study less of a burden to participants?

One example of making studies more patient-centric is to reduce the patient travel burden. Clinical trials that leverage remote technology and decentralization tools to reduce patient time and travel burden may increase the patient consent rate. According to a 2022 IQVIA decentralized clinical trial (DCT) study, DCTs experienced a 78% reduction in recruiting time and a 15% reduction in dropout rates, likely due to the decreased time and travel burden experienced by study participants. This means more diverse trial participants, which can lead to successful outcomes as sub-optimally suited clinical trial participants pose a significant risk to the success of new drug developments.

As a direct-to-patient approach, DCTs allow patients to participate in clinical trials remotely, either through telehealth visits or by having study personnel visit them at their homes. In addition, DCTs can aid in drug supply by enabling more efficient distribution of study medication and supplies – which can be shipped directly to patients’ homes, local labs, or other coordinating sites. This helps improve patient convenience, reduce costs, and potentially speed up trial timelines.

However, DCTs present unique challenges due to the lack of direct physical interaction between investigators and patients. For example, preserving data quality while having more remote interactions and touchpoints compared to an in-person data collection creates the need for new technologies and processes. Apps and wearable devices all have the potential to add more complexity. Since these technologies are still largely in their infancy, their use may present barriers to participants if they ask more of participants than necessary. For example, trying to collect data that exceeds what’s needed for endpoints may add complexity that can adversely impact retention. Another layer of complexity comes in the need to validate and clinically assess those apps to determine whether their data are reproducible and relevant to desired outcomes.

Clinical trial teams also face greater technological challenges as they work with multiple platforms to support different studies. Decentralized trials, therefore, need to feature high-quality logistical and technical support, as well as scientific expertise to ensure study integrity and optimize the patient–investigator experience. The key is to focus on pragmatic ways to incorporate DCT elements into traditional trials.

This speaks to the technology used for trials; they must be able to solve real problems now for sponsors, sites, and patients. Today, several solutions exist that promise a simplified experience, including electronic consent (eConsent) to allow on-site and remote consent, as well as on-site and remote review of consent documentation in a secure environment with consistent compliance. eCOA (electronic clinical outcome assessment) solutions integrate patient outcomes data with robust and secure data collection, standardization, and analysis. Having eConsent, IRT, and eCOA operating within a single platform can also reduce friction for sites and patients. The IRT can leverage the comprehensive data collected in eConsent and eCOA to drive pivotal decisions to improve the patient’s journey throughout the study. This full data visibility helps reduce regulatory risk, study duration, and expenses created by mid-study amendments, alleviating administrative burden while helping patients feel more connected to the study.

Preparing for the Future

Preparing for clinical trials is now more critical than ever as sponsors strive to create efficient, focused, and successful studies. As biopharmaceutical companies continue to adjust to this new de-risking environment, they must embrace a practical yet innovative outlook that will help them stay competitive in an ever-evolving landscape. This means leveraging existing infrastructure to modernize workflows and utilizing proven technology products to make informed decisions.

While the financial pressures leading to the current overall climate of de-risking in clinical trials present unique challenges, they also provide an opportunity for biopharmaceutical companies to reduce risk by improving their development processes. By focusing on fewer, higher quality trials supported by flexible and practical technology, sponsors can ensure that they are making the best possible use of their resources and getting accurate results from each trial.

Once we are past today’s challenges, risk will remain a part of the clinical trial process – such is the nature of research – so it is the duty of clinical trial communities to ensure risks are managed to provide each trial with the best chance of success. Practical approaches and purposeful innovations that help remove friction from mission-critical moments, such as increasing data collection accuracy and sharpening requirements specific to the trials, can be an important first step toward getting better therapies to patients who need them most.