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Background/aims: Provisions of the Inflation Reduction Act mandating drug price negotiation by the Centers for Medicare & Medicaid Services have been criticized as a threat to pharmaceutical innovation. This study models potential impacts of the Inflation Reduction Act on drug approvals based on the differential contributions of large pharmaceutical companies and smaller biotechnology firms to clinical trials and the availability of capital., Methods: This study examined research and development expense, revenue, and new investment (sale of common and preferred stock) by public biopharmaceutical companies and sponsorship of phased clinical trials in ClinicalTrials.gov. Financial data were incorporated in a model that estimates the number of drugs in each phase and approvals from reported phase-specific costs and transition rates, proportional sponsorship of trials by companies of different size, projected reductions in research and development spending based on company size, and three scenarios by which large companies may allocate reductions in research and development spending among clinical phases: (1) research and development proportionally reduced across phases; (2) research and development disproportionally reduced in phases 2-3; and (3) research and development disproportionately reduced in phases 1-2., Results: Financial data were examined for 1378 public biopharmaceutical companies (2000-2018). Research and development expense was associated with revenue for 79 large companies with market capitalization ≥$7 billion with a 10% reduction in revenue reducing research and development expense by 8.4%. For 1299 smaller companies with market capitalization <$7 billion, research and development was associated with new investment, but not revenue. Smaller companies sponsored 55.2% of phase 1, 55.6% of phase 2, and 49.8% of phase 3 trials in ClinicalTrials.gov 2013-2018. In a model of clinical development that apportions clinical trials between large and smaller companies and determines the number of trials based on research and development resources, 400 drugs entering development produced 47.3 approvals (11.83% rate). A 10% reduction in revenue, reflecting the upper boundary of observed changes 2000-2018, with (1) proportional reduction across phases 1-3 produced 45.1 approvals (4.61% reduction); (2) disproportional reduction of phases 2-3 produced 42.8 approvals (9.55% reduction); and (3) disproportional reduction of phases 1-2 produced 46.9 approvals (0.95% reduction)., Conclusion: This work suggests that the drug price negotiation provisions of the Inflation Reduction Act could have little or no impact on the number of drug approvals. While large pharmaceutical companies may reduce research and development spending, continued research and development by smaller companies and strategic allocation of research and development resources by large companies may mitigate any negative effects of the Inflation Reduction Act., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Drs G.V. and F.D.L. received a grant at Bentley University from the West Health Policy Center. Dr F.D.L. has received grants at Bentley University from the National Biomedical Research Foundation, Institute for New Economic Thinking, and the National Pharmaceutical Council. Drs F.D.L. and G.V. had full access to all of the data in this study.

Importance: Despite their importance to patients, health, and industry, the magnitude of investments in drug research and development (R&D) remain nebulous. New policies require more granular and transparent R&D cost estimates to better balance incentives for innovation and returns to developers., Objective: To estimate per-drug R&D costs using a novel, reproduceable approach and to describe firm-level R&D costs per discrete unit of R&D activity (1 patient-month)., Design, Setting, and Participants: This economic evaluation used cross-sectional data to estimate 2014 to 2019 costs per patient-month. Costs per patient-month were calculated using data from 268 US publicly traded drug developers, contributing 1311 firm-year observations, that were highest ranked by assets or market capitalization, after exclusions. Per-drug costs were calculated from all R&D activity through approval for a cohort of 38 new drugs approved by the US Food and Drug Administration in 2019. Data were analyzed from January 2022 to July 2024., Exposure: R&D activity, measured in terms of clinical trial patient-months., Main Outcomes and Measures: This study used a 2-step approach to estimate R&D costs, first allocating firm-year-level total R&D spending across similarly aggregated patient-months, and then aggregating these incremental costs to estimate drug-level R&D costs per new drug., Results: Among 268 developers assessed, 20 large firms accounted for 80.8% of all patient-months and had 27.4% lower mean and 26.7% lower median costs per patient-month compared with other firms. Each 1% increase in patient-months was associated with a 0.9% increase in R&D costs. R&D costs per new drug were highly skewed, with a lower median (IQR), at $708 million ($247 million to $1.42 billion) than mean (SD), at $1.31 ($1.92) billion, after adjusting for the cost of capital and discontinued products. Without these adjustments, direct costs per new drug were a median (IQR) of $150 ($67.6-$453) million and a mean (SD) $369 of ($684) million. While estimated R&D costs varied in sensitivity analyses, mean costs were always substantially greater than median costs., Conclusions and Relevance: This economic evaluation found median per-drug R&D costs toward the lower end of the range from prior studies, with a mean closer to the middle of the existing range despite the broad scope of included costs. These findings suggest parallel development across indications, adjustment for discontinued products, and a small number of expensive development programs are particularly important drivers of R&D costs.

Abstract: In silico clinical trials, particularly when augmented with artificial intelligence methods, represent an innovative approach with much to offer, particularly in the musculoskeletal field. They are a cost-effective, efficient, and ethical means of evaluating treatments and interventions by supplementing and/or augmenting traditional randomized controlled trials (RCTs). While they are not a panacea and should not replace traditional RCTs, their integration into the research process promises to accelerate medical advancements and improve patient outcomes. To accomplish this, a multidisciplinary approach is needed, and collaboration is instrumental. With advances in computing and analytical prowess, and by adhering to the tenets of team science, realization of such a novel integrative approach toward clinical trials may not be far from providing far-reaching contributions to medical research. As such, by harnessing the power of in silico clinical trials, investigators can potentially unlock new possibilities in treatment and intervention for ultimately improving patient care and outcomes., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/I79 )., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Monetary incentives are commonly used to help recruit trial participants. Some studies have found greater recruitment with larger incentives, while others have found smaller incentives more cost-effective in terms of cost per participant. As part of an implementation study, we compared the impact of four approaches to recruitment, three of which involved phone recruitment with varying financial incentives. Adding modest financial incentives reliably increased the recruitment ratio, and greater incentives increased recruitment more than smaller incentives. However, recruiters required less time to obtain agreement to participate when the greater incentive was offered, and these time savings made the greater incentive cost-saving relative to the smaller incentive and cost-effective relative to no incentive. Our results suggest the possibility of a "sweet spot" for financial incentives, and that trial designers should consider pilot-testing incentive levels in the context of their other recruitment costs to determine whether paying participants more may be cost-saving for trial sponsors., Competing Interests: Declarations. Ethics approval and consent to participate: The Institutional Review Board of the Jesse Brown VA Medical Center approved this study. Consent for publication: NA. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

The purpose of a first-in-human (FIH) clinical trial is to gather information about how the drug or device affects and interacts with the human body: its safety, side effects, and (potential) dosage. As such, the primary goal of a FIH trial is not participant benefit but to gain knowledge of drug or device efficacy, i.e., baseline human safety knowledge. Some FIH clinical trials carry significant foreseeable risk to participants with little to no foreseeable participant benefit. Participation in such trials would be a bad deal for participants, and the research is considered justifiable because of the promise of significant potential social benefit. I argue that there is an ethical tension inherent in risky FIH research and that researchers should fairly compensate risky FIH trial participants. This does not make the risk-benefit outcome more favorable for participants; rather, it amounts to a collective reckoning with the ethical tension inherent in the research., Competing Interests: Declarations. Conflict of interest: I declare not competing or conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The two-trials rule for drug approval requires "at least two adequate and well-controlled studies, each convincing on its own, to establish effectiveness." This is usually implemented by requiring two significant pivotal trials and is the standard regulatory requirement to provide evidence for a new drug's efficacy. However, there is need to develop suitable alternatives to this rule for a number of reasons, including the possible availability of data from more than two trials. I consider the case of up to three studies and stress the importance to control the partial Type-I error rate, where only some studies have a true null effect, while maintaining the overall Type-I error rate of the two-trials rule, where all studies have a null effect. Some less-known P $$ P $$ -value combination methods are useful to achieve this: Pearson's method, Edgington's method and the recently proposed harmonic mean χ 2 $$ {\chi}^2 $$ -test. I study their properties and discuss how they can be extended to a sequential assessment of success while still ensuring overall Type-I error control. I compare the different methods in terms of partial Type-I error rate, project power and the expected number of studies required. Edgington's method is eventually recommended as it is easy to implement and communicate, has only moderate partial Type-I error rate inflation but substantially increased project power., (© 2024 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)

Background: White matter hyperintensities (WMH) and their progression are associated with risk of dementia and stroke, so are an important target for clinical trials. The cost of broad magnetic resonance imaging (MRI) screening to identify eligible individuals, however, limits the feasibility of designing clinical trials targeting WMH. A low-cost retinal or clinical screening measure before MRI could reduce recruitment costs versus an MRI-only screening design in a hypothetical clinical trial., Methods and Results: Data from the Atherosclerosis Risk in Communities study with valid retinal and WMH measurements ( N =1311) were used. To identify a population at greater likelihood of significant WMH on MRI and thus reduce the number of screening MRIs required, we evaluated 3 theoretical prescreening measures: (1) retinal, (2) clinical, (3) combined clinical-retinal. Given a target sample for clinical trials ( N =646), we calculated screening sample sizes based on the proportion within the population having an elevated score for each prescreening measure (separately) multiplied by the proportion of significant WMH among those with that prescreening feature. Recruitment costs were calculated using estimated retinal and MRI cost estimates. Compared with the estimated cost of MRI-only screening (>$4.24 million, requiring MRI on 6526 participants), prescreening for a high clinical score resulted in total cost of $2.47 million, with an initial screening group of 52 778 participants, with MRI in 3801. A high clinical-retinal score cutoff resulted in costs of $2.9 million while requiring 13 572 participants, with 3801 completing MRI., Conclusions: A 2-stage design with low-cost prescreening measures is a promising approach, resulting in reduced theoretical recruitment costs compared with an MRI-only design.

Objectives: Clinical trials are an opportunity for patients to access innovative therapy, but patient inclusion in clinical trials can also result in cost savings for hospitals. Our objective was to evaluate the economic impact of clinical trials drug cost savings in a French academic institution from the perspectives of both the French Health Insurance (FHI) and hospitals., Methods: A retrospective, observational, cost saving analysis was performed on all the clinical trials initiated in our university hospital between 2015 and 2020. Only trials involving an investigational medicinal product were considered. Drug cost savings were defined as the best standard of care, defined in the protocol, whose cost was covered by a sponsor., Results: Of the 646 trials undertaken during the 6 years analysed, 21% (212/646) led to cost savings, mostly driven by the industrial sponsor (92%, €6 984 283/€7 591 612) for a total of €7 591 612 (91% from the FHI's perspective (€6 959 115/€7 591 612)). Oncology trials generated 79.1% (€6 004 966/€7 591 612) of global cost savings, mostly driven by onco-haematology (33.1%, €1 983 146/€6 004 966), onco-pneumology (29.2%, €1 754 333/€6 004 966) and onco-dermatology (23.5%, €1 409 553/€6 004 966) followed by hepatogastroenterology trials (6.9%, €413 113/€6 004 966). Of the 162 drugs, the top 15 generated 75.3% (€5 715 479/€7 591 612) of savings and were grouped together: 12 antineoplastic agents (six per os and six intravenous) and three per os antiviral for hepatitis C., Conclusions: With ever-changing prices and new innovative treatments, such cost avoidance must be regularly evaluated. We provided objective evidence that clinical trials could achieve potential cost savings for the FHI and hospitals, in addition to the potential benefit to patients of having access to innovative investigational medicinal products., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Australia's clinical trials sector is highly productive with continued sector investment needed to enhance research impact. Generating economic evidence alongside trials has the potential to facilitate the implementation of trial results into practice. Ascertaining the use of health economic evaluations alongside clinical trials can assist in determining whether clinical trials fully realize and operationalize their potential to change policy and practice. The aims of this study were to ascertain the uptake of health economic evaluations alongside Australian-led clinical trials and explore associations between uptake and trial characteristics., Methods: This observational study comprised a descriptive analysis of clinical trials registries, a cross-sectional survey of Australian Clinical Trials Alliance (ACTA) networks, and a subgroup analysis of completed acute care trials. Descriptive analyses of trial registrations were conducted, with logistic regressions used to identify predictors of proposing and subsequently publishing a health economic evaluation alongside acute care trials., Results: Few randomized Australian-led clinical trials (11% of 9251) and ACTA network trials (43% of 227) proposed a health economic evaluation. In the subgroup analysis, 22% of the 324 acute care trials and 53% of the 38 ACTA network acute care trials proposed a health economic evaluation. Acute care trials funded by government bodies were significantly more likely to propose and publish a health economic evaluation than those funded by hospitals, universities, and other funders, after adjusting for phase, registration year, primary sponsor type, and comparator., Conclusions: Current uptake of health economic evaluations alongside Australian-led clinical trials is low, with uptake higher among the subset of ACTA network trials. This is despite economic evidence playing an increasingly prominent role in health system management, as well as rising health expenditure, limited budgets, and competing demands. There is significant opportunity to embed health economic evaluations alongside clinical trials, particularly phase 3 trials, to increase research outputs and optimize research translation. Investing in clinical trial networks that support funding for a health economist or a health economic evaluation may be an effective strategy to increase the uptake of health economic evaluations alongside trials., (© 2024. The Author(s).)

Investigator-initiated clinical studies (IICSs), also referred to as non-commercial, academic or independent clinical studies, address important research questions that are usually neglected by industry despite their high societal value. Indeed, industry may direct their focus and resources on studies that will yield results and products that can ultimately generate revenue for the company. Conversely, IICS research questions include (a) refining or getting new indications of available treatments (drug repurposing); (b) optimisation, by comparing various health products or treatment regimens; and (c) innovation, especially for advanced therapies. Multinational IICSs increase the scientific quality of the data by exchange of research ideas, scientific techniques and tools. Participation of patients from different geographical, social and ethnic backgrounds equally adds to the value of study results and yields more generalisable evidence than a study confined to a single geographical location. Multinational IICSs are generally sponsored by non-profit/academic organisations and publicly funded. Funding has been already identified as a main challenge for the conduct IICS and especially for clinical trials (IICTs, IICS where a medical intervention is directly tested). Main barriers to the conduct of multinational IICTs with public funding include: Limitations of budget and duration of the eligibility of costs Lack of flexibility to move funds transnationally Tendering rules Complexity in the reporting of the eligible costs to funders We describe why there is a need to support multinational IICS, what should be their objectives and what are the current funding mechanisms in Europe. Strategies for funding multinational IICS should evolve to mitigate identified barriers, thus facilitating research that can provide answers to highly relevant questions in healthcare which are less likely to be answered by studies funded by the pharmaceutical and medical device industry., (© 2024. The Author(s).)

Competing Interests: NMN reports personal fees from Bristol Myers Squibb, Galapagos, Johnson & Johnson Innovative Medicine, Lilly, SBK Healthcare, and Takeda outside the submitted work; grants from Celltrion, Dr Falk Pharma, Johnson & Johnson Innovative Medicine, Pfizer, Pharmacosmos, and Tillotts Pharma outside the submitted work; and advisory board membership for Bristol Myers Squibb outside the submitted work. SS reports consulting fees from Takeda, AbbVie, Merck, Ferring, Pharmacosmos, Warner Chilcott, Johnson & Johnson Innovative Medicine, Dr Falk Pharma, Biohit, TriGenix, Celgene, and Tillots Pharma outside the submitted work; payment or honoraria from AbbVie, Takeda, Celltrion, Pfizer, Biogen, AbbVie, Johnson & Johnson Innovative Medicine, Merck, Warner Chilcott, and Dr Falk Pharma outside the submitted work; and is co-director of research for the South Asian IBD Alliance. MP reports personal fees from Johnson & Johnson Innovative Medicine and Takeda outside the submitted work; and grants from AstraZeneca, Galapagos, Gilead, Pfizer, and Eli Lilly outside the submitted work. TR reports personal fees from Abbvie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Eli Lilly, Ferring, Galapagos, Gilead, GlaxoSmithKline, Heptares, LabGenius, Novartis, Numab, Johnson & Johnson Innovative Medicine, Pfizer, Roche, Takeda, Union Chimique Belge (UCB), and Xap Therapeutics outside the submitted work; grants from AbbVie outside the submitted work; and fees from data monitoring board membership of UCB outside the submitted work. NMN and MP are supported by the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre (NIHR203312). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

Purpose: It is unknown whether Medicaid expansion under the Affordable Care Act (ACA) or state-level policies mandating Medicaid coverage of the routine costs of clinical trial participation have ameliorated longstanding racial and ethnic disparities in cancer clinical trial enrollment., Methods: We conducted a retrospective, cross-sectional difference-in-differences analysis examining the effect of Medicaid expansion on rates of enrollment for Black or Hispanic nonelderly adults in nonobservational, US cancer clinical trials using data from Medidata's Rave platform for 2012-2019. We examined heterogeneity in this effect on the basis of whether states had pre-existing mandates requiring Medicaid coverage of the routine costs of clinical trial participation., Results: The study included 47,870 participants across 1,353 clinical trials and 344 clinical trial sites. In expansion states, the proportion of participants who were Black or Hispanic increased from 16.7% before expansion to 17.2% after Medicaid expansion (0.5 percentage point [PP] change [95% CI, -1.1 to 2.0]). In nonexpansion states, this proportion increased from 19.8% before 2014 (when the first states expanded eligibility under the ACA) to 20.4% after 2014 (0.6 PP change [95% CI, -2.3 to 3.5]). These trends yielded a nonsignificant difference-in-differences estimate of 0.9 PP (95% CI, -2.6 to 4.4). Medicaid expansion was associated with a 5.3 PP (95% CI, 1.9 to 8.7) increase in the enrollment of Black or Hispanic participants in states with mandates requiring Medicaid coverage of the routine costs of trial participation, but not in states without mandates (-0.3 PP [95% CI, -4.5 to 3.9])., Conclusion: Medicaid expansion was not associated with a significant increase in the proportion of Black or Hispanic oncology trial participants overall, but was associated with an increase specifically in states that mandated Medicaid coverage of the routine costs of trial participation.

Two frequently cited figures by clinical research insiders and observers - the cost of missing a day to generate prescription drug sales and the cost of a day to conduct a clinical trial - are outdated and based on anecdotal evidence. In late 2023, the Tufts Center for the Study of Drug Development conducted empirical research to gather more accurate and granular estimates and to test whether average sales per day have changed over time. 645 drugs launched since 2000, and 409 clinical trial budgets were drawn from commercially available and proprietary data sets and analyzed. The results indicate that a single day equals approximately $500,000 in lost prescription drug or biologic sales, with daily prescription sales for infectious, hematologic, cardiovascular, and gastrointestinal diseases among the highest. The results also show that each year, the average sales per day of prescription drugs and biologics has decreased by approximately $80,000-$100,000. The estimated direct daily cost to conduct a clinical trial is approximately $40,000 per day for phase II and III clinical trials, with those in respiratory, rheumatology, and dermatology having the highest relative daily direct costs., (© 2024. The Author(s), under exclusive licence to The Drug Information Association, Inc.)

Objective: To assess the cost-effectiveness of using cheaper-but-noisier outcome measures, such as a short questionnaire, for large simple clinical trials., Background: To detect associations reliably, trials must avoid bias and random error. To reduce random error, we can increase the size of the trial and increase the accuracy of the outcome measurement process. However, with fixed resources, there is a trade-off between the number of participants a trial can enrol and the amount of information that can be collected on each participant during data collection., Methods: To consider the effect on measurement error of using outcome scales with varying numbers of categories, we define and calculate the variance from categorisation that would be expected from using a category midpoint; define the analytic conditions under which such a measure is cost-effective; use meta-regression to estimate the impact of participant burden, defined as questionnaire length, on response rates; and develop an interactive web-app to allow researchers to explore the cost-effectiveness of using such a measure under plausible assumptions., Results: An outcome scale with only a few categories greatly reduced the variance of non-measurement. For example, a scale with five categories reduced the variance of non-measurement by 96% for a uniform distribution. We show that a simple measure will be more cost-effective than a gold-standard measure if the relative increase in variance due to using it is less than the relative increase in cost from the gold standard, assuming it does not introduce bias in the measurement. We found an inverse power law relationship between participant burden and response rates such that a doubling the burden on participants reduces the response rate by around one third. Finally, we created an interactive web-app ( https://benjiwoolf.shinyapps.io/cheapbutnoisymeasures/ ) to allow exploration of when using a cheap-but-noisy measure will be more cost-effective using realistic parameters., Conclusion: Cheaper-but-noisier questionnaires containing just a few questions can be a cost-effective way of maximising power. However, their use requires a judgement on the trade-off between the potential increase in risk of information bias and the reduction in the potential of selection bias due to the expected higher response rates., (© 2024. The Author(s).)

In the last few decades, developers of new drugs, biologics, and devices have increasingly leveraged digital health technologies (DHTs) to assess clinical trial digital endpoints. To our knowledge, a comprehensive assessment of the financial net benefits of digital endpoints in clinical trials has not been conducted. We obtained data from the Digital Medicine Society (DiMe) Library of Digital Endpoints and the US clinical trials registry, ClinicalTrials.gov. The benefit metrics are changes in trial phase duration and enrollment associated with the use of digital endpoints. The cost metric was obtained from an industry survey of the costs of including digital endpoints in clinical trials. We developed an expected net present value (eNPV) model of the cash flows for new drug development and commercialization to assess financial value. The value measure is the increment in eNPV that occurs when digital endpoints are employed. We also calculated a return on investment (ROI) as the ratio of the estimated increment in eNPV to the mean digital endpoint implementation cost. For phase II trials, the increase in eNPV varied from $2.2 million to $3.3 million, with ROIs between 32% and 48% per indication. The net benefits were substantially higher for phase III trials, with the increase in eNPV varying from $27 million to $40 million, with ROIs that were four to six times the investment. The use of digital endpoints in clinical trials can provide substantial extra value to sponsors developing new drugs, with high ROIs., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: There is increasing interest in the capacity of adaptive designs to improve the efficiency of clinical trials. However, relatively little work has investigated how economic considerations - including the costs of the trial - might inform the design and conduct of adaptive clinical trials., Methods: We apply a recently published Bayesian model of a value-based sequential clinical trial to data from the 'Hydroxychloroquine Effectiveness in Reducing symptoms of hand Osteoarthritis' (HERO) trial. Using parameters estimated from the trial data, including the cost of running the trial, and using multiple imputation to estimate the accumulating cost-effectiveness signal in the presence of missing data, we assess when the trial would have stopped had the value-based model been used. We used re-sampling methods to compare the design's operating characteristics with those of a conventional fixed length design., Results: In contrast to the findings of the only other published retrospective application of this model, the equivocal nature of the cost-effectiveness signal from the HERO trial means that the design would have stopped the trial close to, or at, its maximum planned sample size, with limited additional value delivered via savings in research expenditure., Conclusion: Evidence from the two retrospective applications of this design suggests that, when the cost-effectiveness signal in a clinical trial is unambiguous, the Bayesian value-adaptive design can stop the trial before it reaches its maximum sample size, potentially saving research costs when compared with the alternative fixed sample size design. However, when the cost-effectiveness signal is equivocal, the design is expected to run to, or close to, the maximum sample size and deliver limited savings in research costs., (© 2024. The Author(s).)

Background: Oncology clinical trial enrollment is strongly recommended for patients with cancer who are not eligible for established and approved therapies. Many trials are specific to biomarker-targeted therapies, which are typically managed as specialty pharmacy services. Comprehensive genomic profiling (CGP) of advanced cancers has been shown to detect biomarkers, guide targeted treatment, improve outcomes, and result in the clinical trial enrollment of patients, which is modeled to offset pharmacy costs experienced by US payers, yet payer policy coverage remains inconsistent. A common concern limiting coverage of CGP by payers is the potential of identifying biomarkers beyond guideline-recommended treatments, which creates a perception that insurance companies are being positioned to "pay for research." However, these biomarkers can increase clinical trial eligibility, and specialty pharmacy management may have an interest in maximizing the clinical trial enrollment of members., Objective: To investigate if clinical trial enrollment following liquid biopsy CGP for non-small cell lung cancer (NSCLC) is clinically and/or economically impactful from a payer claims perspective., Methods: Clinical and economic outcomes were studied using a real-world clinical genomic database (including payer claims data) from patients with NSCLC who enrolled in clinical trials immediately following liquid biopsy CGP (using Guardant360) and matched NSCLC patient controls also tested with liquid biopsy CGP., Results: Real-world overall survival was significantly (log-rank P < 0.0001) better for patients enrolled in clinical trials with similar costs of care, albeit with more outpatient encounters among those enrolled compared with matched controls., Conclusions: The results, together with previous analyses, suggest that, in addition to the clinical benefits associated with targeted therapies directed by CGP and other testing approaches, payers and specialty pharmacy managers may consider clinical trial direction and enrollment as a clinical and economic benefit of liquid biopsy CGP and adopt this into coverage decision frameworks and formularies.

Background: Economic evaluations are being conducted with increasing frequency in the maternity care setting, with more randomized controlled trials containing a health economic component. Key emerging criticisms of economic evaluation in maternity care are lack of robust data collection and measurement, inconsistencies in methodology, and lack of adherence to reporting guidelines., Methods: This article provides a guide to the design of economic evaluations alongside clinical trials in maternal health. We include economic concepts and considerations for the maternity setting and provide examples from the UK and Australia., Results: There are many important considerations for the design of economic evaluations alongside clinical trials. To be effective, researchers must select types of economic evaluation, which align with their study objectives; choose an appropriate evaluation perspective, time horizon, and discount rate; and identify accurate ways to measure and evaluate health outcomes and costs., Discussion: This guide is written for noneconomists and can be used for designing economic evaluations to be conducted as a part of clinical trials. We seek to improve the quality, consistency, and transparency of economic evaluations in maternal health., (© 2023 The Authors. Birth published by Wiley Periodicals LLC.)

Aim: This study evaluates the impact created by clinical trial investment and research undertaken by Breast Cancer Trials (BCT)., Methods: The approach involved using the Payback Framework, and included a review of BCT archival information, public health data, a questionnaire sent to BCT members, individual interviews with key informants, a focus group with members of the organization's Consumer Advisory Panel, and case studies of select BCT trials. The evaluation assessed the evidence against the Payback Framework criteria: informing policy and product development, knowledge production, the research system, health and health sector benefits, and broader economic benefits., Results: Analysis using the Payback Framework revealed impact was created in each category and a range of positive outcomes were identified for various stakeholder groups. BCT is maximizing the impact of its research and contributing to a global pool of scientific knowledge by collaborating with over 100 institutions and 820 researchers, yet its benefits go beyond research contributions. Findings highlight strong financial returns from BCT's research program and that BCT has played an important role in enhancing the public perception of clinical trials by promoting participation in trials, educating and empowering participants, and communicating trial outcomes., Conclusion: BCT's clinical trials have had a significant impact on the prevention, detection, treatment, and management of breast cancer. Measuring and reporting impact can be resource intensive but support BCT in remaining accountable to all those invested in the organization and in breast cancer clinical trials, evidencing the multiple dimensions of payback resulting from the organization's research., (© 2024 John Wiley & Sons Australia, Ltd.)

Value of Information (VOI) analyses calculate the economic value that could be generated by obtaining further information to reduce uncertainty in a health economic decision model. VOI has been suggested as a tool for research prioritisation and trial design as it can highlight economically valuable avenues for future research. Recent methodological advances have made it increasingly feasible to use VOI in practice for research; however, there are critical differences between the VOI approach and the standard methods used to design research studies such as clinical trials. We aimed to highlight key differences between the research design approach based on VOI and standard clinical trial design methods, in particular the importance of considering the full decision context. We present two hypothetical examples to demonstrate that VOI methods are only accurate when (1) all feasible comparators are included in the decision model when designing research, and (2) all comparators are retained in the decision model once the data have been collected and a final treatment recommendation is made. Omitting comparators from either the design or analysis phase of research when using VOI methods can lead to incorrect trial designs and/or treatment recommendations. Overall, we conclude that incorrectly specifying the health economic model by ignoring potential comparators can lead to misleading VOI results and potentially waste scarce research resources., (© 2024. The Author(s).)

The cost of drug discovery and development is driven primarily by failure 1 , with only about 10% of clinical programmes eventually receiving approval 2-4 . We previously estimated that human genetic evidence doubles the success rate from clinical development to approval 5 . In this study we leverage the growth in genetic evidence over the past decade to better understand the characteristics that distinguish clinical success and failure. We estimate the probability of success for drug mechanisms with genetic support is 2.6 times greater than those without. This relative success varies among therapy areas and development phases, and improves with increasing confidence in the causal gene, but is largely unaffected by genetic effect size, minor allele frequency or year of discovery. These results indicate we are far from reaching peak genetic insights to aid the discovery of targets for more effective drugs., (© 2024. The Author(s).)

The conduct of clinical trials in paediatrics is essential to improve drug therapy in children. In Europe, paediatric clinical trials have been supported by the European Paediatric Regulation since 2007, but there is still a great need for high-quality clinical trials. The personnel and time required to conduct clinical trials in accordance with EU Regulations 536/2014 and 745/2017 is considerably higher compared to other studies, such as observational studies. It is important that this additional workload for the trial centre is fully compensated, also taking into account EU state aid rules. In paediatric trials, it is necessary to take into account the special requirements of paediatric and adolescent medicine when calculating the additional costs. Within the framework of the pan-European paediatric study network c4c/GermanNetPaeT, a working group dealt with specific aspects of cost calculation in order to support paediatric study centres in internal cost calculation as well as in the subsequent preparation of financing requirements for industrial sponsors or public funders. In several workshops the working group developed a cost calculation template with the content derived from the "Joint recommendations for a total services account as a factor in simplifying contracts" of the Deutsche Hochschulmedizin (DHM, German University Medicine), the Netzwerk der Koordinierungszentren für Klinische Studien (KKS Network, Network of Coordinating Centres for Clinical Trials) and the Verband Forschender Arzneimittelhersteller (vfa, German Association of Research-Based Pharmaceutical Companies). By estimating the specific time required for measures and investigations as part of a sample study, the background to the increased time required was discussed and a list with aspects to be considered for cost calculation was compiled together with the study centres. The paediatrics-specific aspects mentioned in detail are intended to increase understanding of the particular problem of higher costs for clinical trials involving children and adolescents and the need for correspondingly appropriate remuneration. This transparent and comprehensible presentation of the higher financial requirements for both the study centres and the financial supporters is intended to promote the high-quality conduct of clinical trials in paediatric study centres in the long term., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024 Ahne et al.)

Background: The dissemination of clinical trial results is an important scientific and ethical endeavour. This survey of completed interventional studies in a French academic center describes their reporting status., Methods: We explored all interventional studies sponsored by Rennes University Hospital identified on the French Open Science Monitor which tracks trials registered on EUCTR or clinicaltrials.gov, and provides an automatic assessment of the reporting of results. For each study, we ascertained the actual reporting of results using systematic searches on the hospital internal database, bibliographic databases (Google Scholar, PubMed), and by contacting all principal investigators (PIs). We describe several features (including total budget and numbers of trial participants) of the studies that did not report any results., Results: The French Open Science Monitor identified 93 interventional studies, among which 10 (11%) reported results. In contrast, our survey identified 36 studies (39%) reporting primary analysis results and an additional 18 (19%) reporting results for secondary analyses (without results for their primary analysis). The overall budget for studies that did not report any results was estimated to be €5,051,253 for a total of 6,735 trial participants. The most frequent reasons for the absence of results reported by PIs were lack of time for 18 (42%), and logistic difficulties (e.g. delay in obtaining results or another blocking factor) for 12 (28%). An association was found between non-publication and negative results (adjusted Odds Ratio = 4.70, 95% Confidence Interval [1.67;14.11])., Conclusions: Even allowing for the fact that automatic searches underestimate the number of studies with published results, the level of reporting was disappointingly low. This amounts to a waste of trial participants' implication and money. Corrective actions are needed., Trial Registration: https://osf.io/q5hcs., (© 2024. The Author(s).)

Patients from historically under-represented racial and ethnic groups are enrolled in cancer clinical trials at disproportionately low rates in the USA 1-3 . As these patients often have limited English proficiency 4-7 , we hypothesized that one barrier to their inclusion is the cost to investigators of translating consent documents. To test this hypothesis, we evaluated more than 12,000 consent events at a large cancer centre and assessed whether patients requiring translated consent documents would sign consent documents less frequently in studies lacking industry sponsorship (for which the principal investigator pays the translation costs) than for industry-sponsored studies (for which the translation costs are covered by the sponsor). Here we show that the proportion of consent events for patients with limited English proficiency in studies not sponsored by industry was approximately half of that seen in industry-sponsored studies. We also show that among those signing consent documents, the proportion of consent documents translated into the patient's primary language in studies without industry sponsorship was approximately half of that seen in industry-sponsored studies. The results suggest that the cost of consent document translation in trials not sponsored by industry could be a potentially modifiable barrier to the inclusion of patients with limited English proficiency., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Deployment of remote and virtual clinical trial methods and technologies, referred to collectively as decentralized clinical trials (DCTs), represents a profound shift in clinical trial practice. To our knowledge, a comprehensive assessment of the financial net benefits of DCTs has not been conducted., Methods: We developed an expected net present value (eNPV) model of the cash flows for new drug development and commercialization to assess the financial impact of DCTs. The measure of DCT value is the increment in eNPV that occurs, on average, when DCT methods are employed in comparison to when they are not. The model is populated with parameter values taken from published studies, Tufts CSDD benchmark data, and Medable Inc. data on DCT projects. We also calculated the return on investment (ROI) in DCTs as the ratio of the increment in eNPV to the DCT implementation cost., Results: We found substantial value from employing DCT methods in phase II and phase III trials. If we assume that DCT methods are applied to both phase II and phase III trials the increase in value is $20 million per drug that enters phase II, with a seven-fold ROI., Conclusions: DCTs can provide substantial extra value to sponsors developing new drugs, with high returns to investment in these technologies. Future research on this topic should focus on expanding the data to larger datasets and on additional aspects of clinical trial operations not currently measured., (© 2022. The Author(s).)

Introduction: Considerable challenges in the economic evaluation of precision medicines have been mentioned in previous studies. However, they have not addressed how an economic assessment would be conducted based on basket trials (novel studies for evaluation of precision medicine effects) in which the included populations have specific biomarkers and various cancers. Since basket trial populations have remarkable heterogeneity, this study aims to investigate the concept of heterogeneity and specific method(s) for considering it in economic evaluations through guidelines and studies that could be applicable in economic evaluation based on basket trials., Area Covered: We searched PubMed, Web of Science, Scopus, Google Scholar, and Google to find studies and pharmacoeconomics guidelines. The inclusion criteria included subjects of patient heterogeneity and suggested explicit method(s). Thirty-nine guidelines and 43 studies were included and evaluated. None of these materials mentioned disease types in a target population as a factor causing heterogeneity. Moreover, in economic evaluations, patient heterogeneity has been considered with four general approaches subgroup analysis, individual-based models, sensitivity analysis, and regression models., Expert Opinion: Type of disease is not considered a contributing factor in population heterogeneity, and the probable appropriate method for this issue could be individual-based models.

Importance: Effective COVID-19 vaccines and therapeutics reached the market within the first year of the pandemic. This rate of development and availability was an unprecedented achievement that required attention to numerous research and development, regulatory, and policy challenges. However, only limited evidence is currently available on the sources of funding for COVID-19 clinical trials., Objective: To compare the number and funding sources of clinical trials aimed at investigating therapeutics and vaccines for COVID-19 vs those for all non-COVID-19 indications., Design, Setting, and Participants: In this cross-sectional study, clinical trials in phase 1 to 3 that were registered to start between January 1, 2020, and August 31, 2021, were examined. All relevant data were collected from ClinicalTrials.gov., Main Outcomes and Measures: Number of clinical trials and their funding sources., Results: A total of 1977 clinical trials that addressed COVID-19 therapeutics and vaccines were registered worldwide with starting dates from January 1, 2020, to August 31, 2021. This cohort represented 13.9% of all trials (N = 14 274) during the same period. Most of the COVID-19 therapeutic and vaccine clinical trials were funded by public sources (1144 [57.9%]), followed by industry (540 [27.3%]) and public-private partnerships (293 [14.8%]). Most of these studies focused on the development of anti-COVID-19 therapeutics (1680 [85.0%]) rather than vaccines (297 [15.0%])., Conclusions and Relevance: The findings of this study suggest that publicly funded research and medical institutions played a leading role as funding sources for generating effective COVID-19 therapeutics and vaccines during the first 1.5 years of the pandemic and were most likely instrumental in their rapid development. It may be beneficial for the public sector to maintain the affordability and global access to these therapeutics and vaccines to ensure that they remain available for use worldwide.

Background: Evidence to support the use of many retention strategies in clinical trials is lacking. Despite this, trial teams still need to have some form of retention strategy in their trials to try and avoid high attrition rates. This study aimed to estimate how much this lack of retention evidence might be costing trials in Ireland and the UK., Methods: We selected the top ten most routinely used retention strategies by Clinical Trial Units in the UK and made assumptions as to how each of these strategies was most likely to be implemented and the costs involved in doing this. We applied our costing model to a hypothetical trial scenario in both Ireland and the UK as well as to three published trial protocols. We developed the costing model and calculated the costs in Microsoft Excel., Results: Retention strategies were often poorly specified, meaning we had to make assumptions about implementation and in some cases about the strategy itself. Based on our assumptions, some retention strategies can be extremely expensive; some of the costliest strategies included "data collection scheduled with routine care" (€900-€32,503.25), "a timeline of participant visits for sites"-with integrated participant reminder (€304.74-€14,803.70), and "routine site visits by CTU staff" and "investigator meetings face to face", both costing (€777.67-€14,753.48). Others such as "telephone reminders for questionnaire response" (€34.58-€568.62), "a timeline of participant visits for sites"-site reminder alone (€79.18-€112.23), and "targeted recruitment of sites/GPs" (€30-€1620) were less costly compared to the other strategies., Discussion: The resources invested in the use of some retention strategies may outweigh known or imagined benefits on retention. Where benefits are currently unknown, evaluation should be a priority., Conclusion: More evaluation of the effectiveness and cost of trial retention strategies is needed to avoid widespread use of strategies that are both expensive and ineffective., (© 2022. The Author(s).)

Reimbursement of participants in clinical trials is extensively debated. Guidance recommends that compensation should reflect time, inconvenience and reimbursement of expenses. This study describes how participants spend their reimbursement and perceptions of appropriate reimbursement amounts. This was a sub-study of the evidence for contraceptive options and HIV outcomes (ECHO) trial. Participants were from two sites in KwaZulu-Natal, South Africa. A mixed methods approach was used. 500 participants completed a questionnaire, and 32 participated in one of four focus group discussions (FGD). The majority (81%) used reimbursement for transport to the research site, followed by toiletry purchases (64%). Many described how reimbursement supplemented income, used to cover basic living costs. Some used money to buy luxury items and takeaway foods. The ideal reimbursement amount per visit ranged: ZAR150-ZAR340 (US$10-24). Reimbursement spending and perceptions are in line with local guidance. Reimbursement should consider risk minimization together with ensuring informed, voluntary decision making., (© 2021. The Author(s).)

Objective: To characterize the interventional clinical trials in infertility and to assess whether trial location or industry sponsorship was associated with trial noncompletion., Design: Retrospective review of trials registered with ClinicalTrials.gov., Setting: None., Patient(s): None., Intervention(s): None., Main Outcome Measure(s): Descriptive statistics characterizing the attributes of the clinical trials including intervention type, topic, population, completion status, size, location, sponsor, and results. The effects of the sponsor and trial location on trial noncompletion were assessed via logistic regression., Result(s): In total, 505 trials initiated between 2010 and 2020 were included in our analysis. Drug interventions were the most commonly studied (45%); ovarian stimulation trials accounted for 27% of the studies. Live birth was tracked as an outcome by 20% of the studies; 3% of the trials included mental health outcomes. Few trials (15%) enrolled male participants. Only 11% of the trials reported results, and 4% of the trials reported the race or ethnicity of the participants. Most trials (82%) were conducted outside the United States. Overall, 18% of the trials were not completed, most often because of lack of accrual (47%). United States trials had over twice the odds of noncompletion in univariate analysis (odds ratio = 2.48, 95% confidence interval = [1.47, 4.17]); however, this relationship lost significance after adjusting for potential confounders (odds ratio = 0.95, 95% confidence interval = [0.42, 2.14]). Trial sponsorship was not associated with trial noncompletion., Conclusion(s): Infertility trials predominantly investigated drug interventions, particularly ovarian stimulation. Live birth was an infrequent outcome despite its relevance to patients. Clinical trials should aim to address the unmet needs in fertility care and be inclusive of underserved populations affected by infertility., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The global burden of cancer is estimated to be more than 20 million cases by 2030, the majority occurring in low- and middle- income countries (LMICs). LMICs account for 64% of global cancer deaths and 80% of disability-adjusted-life-years lost. Despite this, only 5% of the global cancer resources are spent in LMICs causing a high mortality-to-income ratio. Despite the burgeoning number of clinical trials in the HICs, there are several reasons to conduct clinical trials in LMICs. In this commentary, we discuss the problem of access to clinical trials in LMICs using India as a case study.

Introduction: There is a crucial need to perform clinical trials in pediatrics due to an increased prescription rate of unapproved drugs. Since pediatricians are the gatekeepers of clinical trials, the primary objective of the current study was to evaluate, for the first time in France, pediatricians' views on performing clinical trials. The second objective was to identify the factors that influence their perceptions., Material and Methods: In 2017, pediatricians who were members of the French Pediatric Society completed an online survey comprising 27 questions. Fisher's exact test was performed to evaluate possible correlations between pediatrician characteristics (age, sex, parenthood, professional experience, status, type of practice, previous participation in clinical trials, ethics education) and personal views on clinical trials. A value of P≤0.001 was considered statistically significant., Results: Overall, 207 pediatricians completed the questionnaire. Almost all participants (96.6%) were in favor of performing clinical trials. Pediatricians with teaching experience at university hospitals were more reluctant to propose children's participation in clinical trials for fear of increasing parental stress (P<0.001), or the occurrence of serious adverse reactions (P<0.001). Pediatricians with coordinator or investigator experience considered that one of the ethical drifts in pediatric clinical trials is the risk of child exploitation (P<0.001)., Conclusion: Our findings suggest a favorable position of pediatricians concerning clinical trials, despite numerous concerns. Another outcome is the need to create an educational system of research in ethics in France dedicated to pediatricians in order to guarantee good clinical practice in research., (Copyright © 2021 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

The proposed triple aim of health care-enhanced patient experience, improved population health, and reduced per capita costs-can be applied to clinical research. A triple aim for clinical research would (1) improve the individual research participant's experience; (2) promote the health of populations; and (3) reduce per capita costs of clinical research. Such an approach is possible by designing trials around the needs of participants rather than sites, embracing digital measures of health, and advancing decentralized studies. Recent studies, including those evaluating therapies for COVID-19, have demonstrated the value of such an approach. Accelerating the adoption of these methods can help fulfill this new triple aim of clinical research.

Background: Clinical trials are often perceived as being expensive, difficult and beyond the capacity of healthcare workers in low-resource settings. However, in order to improve healthcare coverage, the World Health Organization (WHO) World Health Report 2013 stated that all countries need to become generators as well as recipients of data. This study is a methodological examination of the steps and processes involved in setting up the Gojjam Lymphoedema Best Practice Trial (GoLBeT; ISRCTN67805210), a highly pragmatic clinical trial conducted in northern Ethiopia. Challenges to the trial and strategies used to deal with them were explored, together with the reasons for delays., Methodology and Principal Findings: Qualitative research methods were used to analyse emails and reports from the period between trial inception and recruitment. This analysis was complemented by interviews with key informants from the trial operational team. The Global Health Research Process Map was used as a framework against which to compare the steps involved in setting up the trial. A mini-group discussion was conducted with the trial operational team after study completion for reflection and further recommendations. This study showed that the key areas of difficulty in setting up and planning this trial were: the study design, that is, deciding on the study endpoint, where and how best to measure it, and assuring statistical power; recruitment and appropriate training of staff; planning for data quality; and gaining regulatory approvals. Collaboration, for example with statisticians, the trial steering committee, the study monitors, and members of the local community was essential to successfully setting up the trial., Conclusions and Significance: Lessons learnt from this trial might guide others planning pragmatic trials in settings where research is not common, allowing them to anticipate possible challenges and address them through trial design, planning and operational delivery. We also hope that this example might encourage similar pragmatic studies to be undertaken. Such studies are rarely undertaken or locally led, but are an accessible and efficient way to drive improved outcomes in public health., Competing Interests: The authors have declared that no competing interests exist.

With billions of dollars in research and development (R&D) funding continuing to be invested, the novel coronavirus disease 2019 (COVID-19) has become into a singular focus for the scientific community. However, the collective response from the scientific communities have seen poor return on investment, particularly for therapeutic research for COVID-19, revealing the existing weaknesses and inefficiencies of the clinical trial enterprise. In this article, we argue for the importance of structural changes to existing research programs for clinical trials in light of the lessons learned from COVID-19., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: COVID-19 pandemic caused several alarming challenges for clinical trials. On-site source data verification (SDV) in the multicenter clinical trial became difficult due to travel ban and social distancing. For multicenter clinical trials, centralized data monitoring is an efficient and cost-effective method of data monitoring. Centralized data monitoring reduces the risk of COVID-19 infections and provides additional capabilities compared to on-site monitoring. The key steps for on-site monitoring include identifying key risk factors and thresholds for the risk factors, developing a monitoring plan, following up the risk factors, and providing a management plan to mitigate the risk., Methods: For analysis purposes, we simulated data similar to our clinical trial data. We classified the data monitoring process into two groups, such as the Supervised analysis process, to follow each patient remotely by creating a dashboard and an Unsupervised analysis process to identify data discrepancy, data error, or data fraud. We conducted several risk-based statistical analysis techniques to avoid on-site source data verification to reduce time and cost, followed up with each patient remotely to maintain social distancing, and created a centralized data monitoring dashboard to ensure patient safety and maintain the data quality., Conclusion: Data monitoring in clinical trials is a mandatory process. A risk-based centralized data review process is cost-effective and helpful to ignore on-site data monitoring at the time of the pandemic. We summarized how different statistical methods could be implemented and explained in SAS to identify various data error or fabrication issues in multicenter clinical trials., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Objectives: The Best Pharmaceuticals for Children Act (BPCA) incentivizes the study of on-patent medicines in children and mandates that the National Institutes of Health sponsor research on off-patent drugs important to pediatric therapeutics. Failing to enroll cohorts that reflect the pediatric population at large restricts the generalizability of such studies. In this investigation, we evaluate racial and ethnic minority representation among participants enrolled in BPCA-sponsored studies., Methods: Data were obtained for all participants enrolled in 33 federally funded studies of drugs and devices conducted from 2008 through June 2020. Observed racial and ethnic distributions were compared with expected distributions by sampling Census data at the same geographic frequency as in the studies. Racial and ethnic enrollment was examined by demography, geography, study type, study burden, and expected bias. Standard descriptive statistics, χ 2 , generalized linear models, and linear regression were applied., Results: A total of 10 918 participants (51% male, 6.6 ± 8.2 years) were enrolled across 46 US states and 4 countries. Studies ranged from treatment outcome reviews to randomized, placebo-controlled trials. Minority enrollment was comparable to, or higher than, expected (+0.1% to +2.6%) for all groups except Asian Americans (-3.7%, P < .001). American Indian and Alaskan Native and multiracial enrollment significantly increased over the evaluation period ( P < .01). There were no significant differences in racial distribution as a function of age or sex, although differences were observed on the basis of geography, study type, and study burden., Conclusions and Relevance: This study revealed no evidence of racial and ethnic bias in enrollment for pediatric studies conducted with funding from BPCA, fulfilling the legislation's expectation to ensure adequate representation of all children., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Abdel-Rahman, Ms Delmore, and Drs Hornik, Paul, Sullivan, Wade, and Zimmerman serve as members of the steering committee for the Pediatric Trials Network, which receives Best Pharmaceuticals for Children Act funding from the Eunice Kennedy Shriver National Institute for Child Health and Human Development. Dr Benjamin serves as the PI of the Pediatric Trials Network. At the time of writing Dr Sharma was employed by the Best Pharmaceuticals for Children Act data coordinating center., (Copyright © 2021 by the American Academy of Pediatrics.)

Background: The business of clinical research has changed in the past two decades, shifting from industrialised Western countries to so-called emerging markets such as Eastern Europe, Latin America and Africa. An appraisal of the trends could identify associated factors that may have implications for the local populations and their endemic diseases., Objectives: To identify potential reasons why emerging countries have become attractive places for international sponsors to conduct their clinical trials., Methods: Using ClinicalTrials.gov, the Pan African Clinical Trials Registry, the National Health Research Database and the Nigeria Clinical Trials Registry, trend data on clinical research development were determined for two emerging African markets, Nigeria and South Africa (SA), from 2010 to 2018. Also, health data on the two countries from the fact sheets of health statistics of the World Health Organization were compared, as well as regulatory and ethical conditions. Available data were analysed using descriptive statistics and trend analysis., Results: The impact of globalisation is evident from the upward trend in clinical trials in SA before 2010, and the clear downward trend thereafter. One reason for this change could be the alignment of SA's regulatory and ethical frameworks with the Western world. In contrast, the upward trend is only just beginning in Nigeria, with the introduction of ethical/regulatory frameworks, and supportive institutions making the business of clinical research more attractive on an international level. Although the number of international and local sponsors increased in Nigeria from 2010 to 2018, only the latter increased in SA, with the former decreasing over the same period. Overall, there is a mismatch between country-specific diseases and the drugs being tested, to the extent that leprosy, which is endemic in Nigeria, and tuberculosis in SA were not in the list of top 10 study areas in either country., Conclusions: The globalisation trend is evident in the clinical trials business, but cannot be generalised to all emerging countries. Timing and intensity vary from country to country relative to factors that advance the existing profit-orientated business models of the sponsors. Furthermore, various diseases have been localised, which entails a diversely increasing need for research.