This study quantified the costs and durations of clinical trials conducted by Japanese pharmaceutical companies, using the most recent actual data from each company. In drug development, the probability of success from the start of Phase 1 to approval is approximately 10% [1, 3]. Bringing a single new drug to market is estimated to cost billions of dollars, including investments in failed projects during the research and development process [2]. This study focused on actual phase unit costs, differentiating them from the estimated overall cost accounting for the probability of success. Challenges in accurately collecting data for some projects in this survey, including those still determining whether to proceed to the next phase, prevented precise estimates of success probability for phase progression. Limited data indicated an overall success probability from Phase 1 to approval of 14.6%. These results provide insights into the investment risks faced by Japanese pharmaceutical companies in research and development aimed at bringing new drugs to the market.

The cost findings of this study are consistent with or slightly higher than those reported in previous studies using data from USA or global pharmaceutical companies, considering a median annual average exchange rate of 109 JPY per USD during the study period [7, 8]. Among them, clinical trials targeting global approval, including those in the USA or Europe, had a median Phase 3 cost of 8,083 million JPY, identifying them as a higher-cost subgroup. Factors influencing this result may include relatively large-scale projects targeting the USA or Europe among those undertaken by Japanese pharmaceutical companies, inherently high site payments in North America, and increased outsourcing costs associated with accessing foreign sites from Japan. The estimated costs per site for clinical trials are quantitatively higher in North America than those in other regions [15]. Pharmaceutical companies must consider overall clinical trial costs when making investment decisions. Assuming all phases from Phase 1 to Phase 3 are conducted, the estimated overall cost for the clinical trial is 6,781 million JPY, on the basis of the sum of the median costs for each phase in this study. Phase 3 costs correlated with Phase 1 and Phase 2 costs, indicating that clinical trials with higher Phase 1 or Phase 2 costs tend to have higher Phase 3 costs. Projects incurring high costs in any phase are likely to observe escalating costs in subsequent phases, thereby increasing the overall clinical trial cost. The median annual research and development expenditure of 21 major Japanese pharmaceutical companies in 2022 was approximately 63 billion JPY [16]. Given this limited budget, funds must be allocated to appropriate projects. Specifically, for global projects, investment decisions for clinical trials are made cautiously, considering the probability of success, as the total cost may surpass 10 billion JPY when all phases from Phase 1 to Phase 3 are conducted. Approximately 10% of new drugs approved in Japan were not approved internationally, with most of these drugs being produced by Japanese pharmaceutical companies [17]. If Japanese pharmaceutical companies hesitate to invest in global development, essential drugs may not be marketed in other countries. A marginal correlation was observed between higher trial costs and projects with annual sales forecasts exceeding 10 billion JPY for the Japanese market. Conversely, projects with annual sales forecasts below 2 billion JPY showed lower costs, suggesting that decisions to undertake costly projects with significant costs may be influenced by expected returns, as projects with higher sales forecasts justify larger budgets.

Regarding durations, the findings of this study largely align with those reported in studies using global data, although Phase 3 durations were slightly shorter [9]. No project parameters had a strong impact on the overall phase duration. The correlation coefficients between projects targeting approval involving the USA or Europe and phase durations of each phase fell within the range from 0.08 to 0.15, showing no meaningful relationships. In contrast, correlation coefficients with costs for each phase ranged from 0.28 to 0.42, indicating a stronger relationship between costs and phase durations. Several studies have linked trial duration to therapeutic areas, particularly in oncology [9, 18]. While this study also identified a trend of longer oncology trials compared with others, no notable differences were observed. Given that this study did not focus on a specific therapeutic area, the limited number of projects in certain therapeutic areas may have influenced the results. The correlation between cost and duration, without accounting for other parameters, showed a stronger relationship in the earlier phases. Factors such as extended observation periods for participants, delays in case enrollment, and prolonged preparation for subsequent phases or applications contribute to increasing clinical trial costs [10, 19, 20]. If the impact of duration on costs remains constant across phases, these correlation coefficients suggest that cost variations in later phases may be influenced by more significant factors.

A strength of this study is the large-scale, questionnaire-based survey that quantified clinical trials conducted by Japanese pharmaceutical companies. Limitations include the lack of access to more detailed clinical trial information, such as the number of patients enrolled, number of sites, number of countries, frequency of visits, and size of the conducting company. This information was restricted to protect trade secrets, and the absence of these parameters may have impacted cost and duration estimates. Additionally, confidential information, such as sales forecasts, was often missing, making it difficult to estimate these values. The limited data also complicated efforts to impute missing values. Once all relevant parameters are available, the marginal effects on trial costs and durations can be accurately estimated using multivariable regression. The survey was conducted retrospectively using each company’s database. As these databases are optimized independently and not in a common format, this may have led to variations in the information provided. To minimize potential bias and standardize answers across companies, we conducted a question-and-answer session with respondents from each company. Although this study focused exclusively on clinical trials, research on drug discovery also presents investment risks for pharmaceutical companies. Further research is necessary to understand the overall burden of drug discovery and development on companies in Japan.