Addressing Clinical Trial Challenges and High Drug Development Costs

May 25, 2023 - The drug development process is a notably tricky component of the pharmaceutical industry, accounting for the most time and money required to get a drug to market. Across the United States, the average spending on drug development is roughly $2 billion. While critical for approval by the US Food and Drug Administration (FDA), the cost of pharmaceutical research presents a barrier to advancements and pharmaceutical innovations. To circumvent these barriers, clinical researchers must address the drug discovery and clinical trial challenges linked to high drug development costs.

The FDA identifies five parts of the drug development life cycle: discovery and development, preclinical research, clinical research, FDA review, and FDA post-market safety monitoring.

Accounting for research and development, the Government Accountability Office estimates that a new drug’s development life cycle can take 10–15 years and billions of dollars. Regardless of the time and money drug companies spend on research, a medicine may not receive regulatory approval, sending researchers back to the drawing board.

Beyond failing to determine appropriate drug candidates in the discovery and development phases, the FDA notes that 30% of pharmaceutical products that reach phase I clinical trials do not make it to phase II. In phase II, a considerable proportion of new medicines fail, with only one-third transitioning to phase III. Another 70–75% of drugs will fail in phase III before reaching phase IV.

Despite challenges to FDA approval, the process requires pharmaceutical companies to ensure that they are producing safe and effective drugs or therapies.

Complex Clinical Trials and Failure Risk

When looking at more complex treatment types, a layer of complexity is added to the regulatory cycle. Arda Ural, EY Americas Industry Markets Leader for Health Sciences and Wellness, told PharmaNewsIntelligence that there is a growing focus on gene therapies and mRNA technologies.

“Cell and gene therapy is a hot focus area, with more than 1,800 assets already in clinical-stage development. Gene editing is also a very attractive area, as it has curative outcomes if successful,” he said. “RNA-based therapies are also rapidly gaining prominence, with more than 200 RNA products in clinical trials for various illnesses including oncology, flu vaccine, respiratory disease, and heart failure.”

According to a 2019 study published in Value in Health, the widely accepted drug development process was primarily built to account for small-molecule drugs rather than biologics. While the FDA has worked to adapt existing drug approval protocols to accommodate new gene therapies, biologics, biosimilars, and biotechnology, they may not meet the demands of these more complex treatment options.

“Some of the common conditional diseases are already commoditized, and some of the less understood diseases are attracting more innovation focus,” Ural explained. “The challenge will be for research teams to develop not only differentiated assets but successfully leverage complex technologies that can advance these therapies to phase III trials.”  

He postulates that phase III clinical trials, which enroll a global patient population of up to 3,000 individuals to confirm the safety and efficacy of the drug, will remain a critical focus and challenge in the drug development process for more complex treatments.

“A phase III clinical trial is the most important stage in drug discovery and development, as fewer products are reaching that stage. Failing a phase III asset would lead to a massive value erosion — ultimately, an expensive failure,” Ural continued.  

New drug developments for complex and rare diseases often require newer and less understood drugs often require technology that may be new or not as well-established.

“Complex disease areas are typically supported by more complex innovations and emerging technologies,” Ural said. “These assets tend to experience higher failure rates than those in traditional disease areas such as anti-infectives, respiratory, and gastrointestinal when developing new treatments.”  

High Drug Development Costs

In addition to the high risk of failure, the development process for new prescription drugs has an exorbitantly high cost. Beyond the high prices of finding the appropriate drug component or formulation, various expenditures are linked to clinical trials.

For example, when developing a clinical trial budget, researchers and sponsors must consider administrative, time, site, data collection, data analysis, procedural, patient care, and personnel costs. Without an adequately budgeted clinical trial with clear endpoints, there is no way to generate real-world data that justifies regulatory approval.

Artificial Intelligence and Machine Learning

Researchers have begun integrating artificial intelligence and machine learning (AI/ML) into the pharmaceutical research process to minimize the cost of developing a new drug.

A recent study published in Drug Discovery Today found that AI can reduce the time needed to develop a new drug by up to 50%. As a result, the cost of drug development may decrease by up to $26 billion annually. Another incentive for AI use in clinical research is its ability to model the safety and efficacy of drug molecules using deep learning.

Decentralized Clinical Trials

Another critical tool for healthcare researchers has been decentralized clinical trials to decrease the need for clinic visits and minimize spending on those factors.

An EY-Parthenon poll of 69 sponsor pharmaceutical companies, biotech companies, and contract research organization (CRO) decision-makers revealed that half of biopharmaceutical clinical trials are expected to become hybrid or completely decentralized by 2024.  

“The adoption of hybrid and DCT approaches will be driven by improvements in regulatory communication and advancements in data integration and usability,” Ural said. “Sponsors, CROs, and vendors should take the steps now to address these gaps.”  

Mergers and Acquisitions

Mergers and acquisitions across different therapeutic areas may also be advantageous in addressing higher R&D costs and improving success rates.

Beyond mergers in cancer drugs, neurology, and other spaces, Ural identified potential growth and development in rare diseases. Despite 7,000 known rare diseases, only 10% have a widely available treatment option, presenting an unmet healthcare need.

Rather than a standard new drug application, rare disease medications are eligible for orphan drug designation.

“Executives should consider pursuing strategic bolt-on acquisitions to drive portfolio value and acquire novel therapies, especially in adjacent therapeutic areas,” Ural said.   

“Relatively small bolt-on deals of less than $1B in value in existing or adjacent therapeutic areas are likely to have higher success rates, suggesting that when scanning acquisition targets, acquirers should seek bolt-on deals that align with current portfolio areas to foster success in scaling new assets and technologies,” he continued.  

At the time of this interview, Ural predicted that the exclusivity of these drugs and limited options could allow manufacturers to charge higher prices and still be reimbursed. However, recent rhetoric surrounding genomics, gene therapy, and other rare disease drugs suggests that list prices are getting out of hand. Many sources predict that health insurance providers and payers cannot keep up with the never-ending rise in drug prices.

While health policy only provides price restrictions for public insurers, such as Medicaid or Medicare, policymakers and members of Congress have discussed developing policies to combat high drug costs.

No matter how policy changes, pharmaceutical companies, healthcare leaders, researchers, and public health experts must develop strategies to improve the cost-effectiveness of clinical trial protocols. The healthcare sector can achieve lower costs through partnerships, technological assessment or advancement, and policy change.