Part 1. The Erosion: How American Biotech Lost Its Preeminence

By Michelle Longmire, MD

Imagine it is a Tuesday in March 2035, and you have just been diagnosed with glioblastoma, an aggressive brain cancer. Your neuro-oncologist walks you through the standard of care, the Stupp protocol, a regimen that has changed remarkably little in thirty years with a median survival measured in months.

You ask about clinical trials. There is, in fact, a drug: survival benefit double anything this clinic can offer, documented remissions in advanced disease. It was approved in China twenty-six months ago, and tens of thousands of patients there have already received it. Here, it is still in Phase 3, with an FDA decision expected sometime in 2037. Your institution isn't a trial site, and your oncologist can't tell you how to become a patient at one that is. So you ask the obvious question, how does the United States not have this medicine?

I. The Biotechnology Industry Was Born from American Biomedical Innovation and Capitalism

In 1976, in the San Francisco Bay Area, venture capitalist Robert Swanson and scientist Herbert Boyer founded Genentech and turned a laboratory result into an industry.1 The underlying breakthrough was American as well: Boyer at UCSF and Stanley Cohen at Stanford had developed recombinant DNA technology, splicing genes into bacteria to produce the world's first genetically modified organisms,2 and with them a route to manufacturing human insulin without reliance on animal-derived sources.3 That innovation launched the biopharmaceutical era.

For half a century thereafter, the United States converted bench science breakthroughs into life changing medicine faster, and more ambitiously, than any other country, and built the machinery that made the conversion repeatable: venture capital, deep public markets, and a regulatory authority whose approvals carry global weight. The returns compounded across five decades in approvals, in company formation, and in the capital markets that recycled successful exits into new science (Figure 1).

FIGURE 1: Fifty Years of Compounding Returns on American Invention

Approximate decade totals. Approvals: FDA CDER novel drug and new-biologic (NME/BLA) approvals. IPOs: U.S. biotech initial public offerings. Acquisitions: biopharma M&A transactions valued at $1B or more. Figures rounded from published annual data; 2016–25 includes a partial 2025. Sources: FDA CDER; BioPharma Dive IPO tracker; Ritter IPO database, University of Florida; industry M&A analyses, 1976–2026.

II. Transforming Science into Medicine

In merely fifty years, the biotechnology industry has grown into a major driver of the trajectory of human health. Emerging biopharmaceutical companies, defined as spending under $200 million on research and development, now originate approximately 85% of newly launched medicines and start about 63% of clinical trials, while large pharmaceutical companies account for roughly 23% of pipeline activity, down from 48% in 2002.4,5 Big pharma has shifted, over time, toward acquiring assets in the later stages of development and carrying them through approval and commercialization. Invention and early risk-taking happen in biotech, while big pharma foots the bill and then reaps the benefits of scale and commercialization.

Biotech companies do not simply produce incremental therapeutic improvements; biotech is where new therapeutic paradigms are born. Genentech made recombinant human insulin manufacturable in 1982, and with Herceptin in 1998 established that a cancer could be treated according to its molecular target rather than its organ of origin. Amgen turned recombinant proteins into an industry with Epogen in 1989 and Neupogen in 1991. Medarex and Bristol Myers Squibb brought checkpoint blockade to patients with Yervoy in 2011, and Merck's Keytruda made immunotherapy the backbone of oncology. Pharmasset's sofosbuvir, carried through development by Gilead, turned hepatitis C from a progressive liver disease into a curable one in 2013. The first CAR-T cell therapies arrived in 2017, from Kite Pharma and from Novartis with University of Pennsylvania science. Vertex addressed the underlying defect in cystic fibrosis with Kalydeco in 2012 and Trikafta in 2019, and with CRISPR Therapeutics delivered the first approved gene-editing therapy in 2023. Moderna showed in 2020 that a vaccine could be designed in days and manufactured at global scale and more recently that personalized cancer vaccines offer important therapeutic leverage in advanced melanoma.4

Each of these breakthroughs redefined an entire disease category and the trajectory of every life diagnosed within it. They are much of the reason the age-adjusted cancer death rate in the United States has fallen by roughly a third since 1991, an aggregate approaching four million deaths that did not occur6, and that HIV, the eighth leading cause of death in America in the early 1990s, now carries a near-normal life expectancy when treated promptly.7

Many believe, myself included, that we are on the eve of the greatest era of medical science in human history. Artificial intelligence has begun to compress target discovery, structure prediction, and molecular design in ways that should unlock the most productive era in the history of American biotechnology. But who will lead the race to translate this science into life-changing medicines? Will it be the country that gave birth to the biotechnology industry, or will it be a new entrant? This essay appears in two parts. Part 1, which follows here, is a call to action: an examination of where American biotechnology is headed and what China’s rise means for our position. Part 2 proposes a new clinical development paradigm aimed at securing the future of American biotechnology as we enter an era with the potential for exponential advancement in human health.

III. American Biotechnology Dominance Is Rapidly Eroding

In 2015, the United States originated roughly 48% of the world's early-stage drug programs and China originated 8%. By 2024 the figures were 37% and 32%.8 China's share of global trial starts rose from a negligible base to near-parity with the United States over the same decade, and by absolute volume China surpassed the United States around 2020, exceeding 5,000 registered trials annually by 2024.9,10 In 2024, a Chinese company, Jiangsu Hengrui, became the world's single largest sponsor of clinical trials, displacing AstraZeneca; and in 2025, for the first time, more drugs made their market debut in China than in any other country, including the United States.11

The pipeline evidence extends beyond volume into modality. Since 2021, Chinese developers have registered nearly twice as many first-in-human trials for next-generation antibodies (bispecifics and antibody-drug conjugates) as the United States and Europe combined. Innovative-drug IND submissions from Chinese developers rose from 688 in 2019 to 2,298 in 2023.12 This is not a low-complexity pipeline pursuing well-trodden targets.13

Origination of a drug program is tightly coupled with expected market access, and here Europe is a cautionary example. As Europe's relative innovation position and pricing environment have deteriorated — its share of global pharmaceutical R&D has fallen by roughly a quarter over two decades — manufacturers have begun deferring, restricting, and in some cases skipping European launches altogether, a trend now accelerating under pricing pressures on both sides of the Atlantic. The EFPIA W.A.I.T. indicator documents average delays of nearly 600 days between approval and patient access, ranging from under two months in Germany to more than three years in Romania, with variation between member states that is wide and widening.14 Nearly half of newly approved medicines are simply unavailable to European patients — medicines already on pharmacy shelves elsewhere.

By 2035, on the trajectory described in this paper, roughly four in five genuinely innovative oncology medicines will have launched first in China, and American patients will wait two to three years behind. If the trends continue, the early-stage origination shares stand at 62% for China against 24% for the United States — a ratio of roughly five to two, making the country that invented the biopharmaceutical industry a secondary market for its output (Figure 2).8

FIGURE 2: The Trend Line, Extended

Share of global early-stage drug development programs. Solid segments are observed endpoints reported by Kang et al., JAMA, 2026 (2015 and 2024). Dashed segments are a linear extrapolation of the observed slopes, shown to make the implication of the current trajectory explicit. This is not a forecast. It assumes no saturation, no policy response, no competitive adjustment, and no change in the underlying cost structures — assumptions that are individually unlikely and collectively the point of this paper. Oncology would be expected to run ahead of the aggregate line, given that Chinese originators already account for roughly nine in ten antibody-drug-conjugate licensing transactions worldwide.

IV. Pharma Is Shopping in China for Innovation

The most consequential signal is not what China develops but what the rest of the industry now buys. Cross-border out-licensing of Chinese-originated assets rose from $13.9 billion in 2021 to a record $137.7 billion in 2025 across approximately 157 transactions — an increase of nearly tenfold in four years.15 First-quarter 2026 alone reportedly reached roughly $60 billion, up 73% year over year.16 China now accounts for roughly a third of global out-licensing deal value, against 21% in 2023–24 (Figure 3).17

FIGURE 3: Where Large Pharmaceutical Companies Are Sourcing Their Pipelines

Annual out-licensing deal value for China-origin assets (bars, left axis) and China's share of global out-licensing deal value (line, right axis). Sources: PharmCube NextBiopharm via Reuters; Vision Life Sciences; industry deal analyses, 2025–2026.

Individual transactions illustrate the scale of investment flowing to biotechnology companies in China. GSK acquired ex-China rights to a Hengrui COPD candidate in a deal valued at up to $12.5 billion; Pfizer licensed 3SBio's oncology candidate SSGJ-707 for $1.25 billion upfront against up to $4.8 billion in milestones.18 Cumulatively, U.S. pharmaceutical companies have committed on the order of $53 billion to licensing arrangements with Chinese biopharmaceutical firms since 2020, and China-originated compounds now constitute roughly one-third of new molecules entering American pipelines — up from virtually none five years ago, with projections reaching 35% of FDA approvals by 2040.19

V. Root Cause: Velocity and Cost, Not Scientific Discovery

What is driving the drug development pivot to China? At face value the answer would seem to be better drug discovery science, the basic science that leads to new therapeutic categories. Recent cuts to basic research funding in the United States pose a threat to the American discovery engine, but they are not what moved a third of the world's early-stage origination to China over the past decade. The pivot to China is driven in large part by Chinese innovation in the clinical development machine: the trials themselves, and the regulatory and operational infrastructure that carries a molecule through testing in humans.

Consider current operating parameters. A Phase 1 trial in China runs approximately seven months against seventeen or more in the United States, with Phase 1 costs 32–52% lower.20 Early discovery-to-IND cycles are estimated to be 50–70% faster, and Phase 1 costs 50–60% lower, than in the rest of the world (Figure 4).10

FIGURE 4: The Mechanism: Velocity and Cost, Not Discovery

Median Phase 1 trial duration, months. Associated differentials: Phase 1 trial costs 32–52% lower; discovery-to-IND cycle times 50–70% faster. Sources: GlobalData, 2026; Cure Innovation Index / Reagan-Udall Foundation, 2026.

VI. How China Actually Wins

China’s velocity advantage is largely operational and systems engineering versus scientific superiority. Three mechanisms drive the current competitive edge.

1. Study startup is treated as a single obligation, not disconnected phases

The intuitive explanation, that Chinese regulators simply approve faster, is not the case. China's implied-approval mechanism, introduced in 2018, deems a clinical trial application approved if the Center for Drug Evaluation raises no objection within 60 working days; a 2025 reform adds an optional 30-working-day track for Class 1 innovative drugs.21 An FDA IND takes effect 30 calendar days after receipt. On the regulatory clock alone, the United States is the faster jurisdiction.

The American disadvantage lies entirely in what surrounds that clock. The Department of Health and Human Services' own 2026 assessment reports that the average interval between a U.S. sponsor's pre-IND meeting request and IND submission is approximately 380 days, with a range approaching 700, and that institutional review board approval and contract negotiation can add as much as thirteen further months before a single patient is enrolled.22 Independent data place median site activation at 9.4 months for academic medical centers and hospitals, against a National Cancer Institute target of 90 days and observed times at NCI-designated cancer centers ranging from 78 to 313 days.23 In one documented multi-site study, contract and budget negotiation alone averaged 41 and 36 weeks respectively.23

China's structural difference is operational: approval and initiation are treated as one continuous obligation. An applicant using the 2025 expedited pathway must commit to initiating the trial within twelve weeks of application.21 The American system optimizes the regulatory decision but not what comes after. Once approval is granted, the pace is set by the policies and procedures of individual institutions and clinical sites, which vary widely and face no government mandated timeframe.

2. The enrollment infrastructure is built for clinical research, not retrofitted

Participant enrollment also favors China, for a structural reason: research there is concentrated in very large medical centers. Trial activity clusters in Grade 3A tertiary hospitals such as Sun Yat-sen University Cancer Center, Fudan University Shanghai Cancer Center, Peking Union Medical College Hospital, and their peers. These institutions combine enormous catchment populations with dedicated research units and direct relationships with principal investigators, so a single site can enroll at a scale that would require dozens of American sites to match.24 In immuno-oncology, roughly 234,000 patients are newly diagnosed annually in the United States compared to approximately 780,000 in China.25 Those patients are also more frequently treatment-naive, which matters materially in oncology, where eligibility criteria routinely exclude prior lines of therapy.

The American clinical research infrastructure is dispersed across many more institutions and clinics, and at the major academic centers where trials do concentrate, dozens of concurrent protocols compete for the same specialist-referred population; roughly 70% of trial-registry patients in developed markets are being approached by more than one study simultaneously.24 American trials do not merely enroll slowly. They often cannibalize one another. Additionally, there is no incentive for a clinician to refer a patient to a trial that is being conducted by a hospital or clinic that is not “in network.” Meaning that even if a patient is an ideal candidate for a trial being run at a nearby clinic there is no incentive to refer a patient. The combined effect is patient recruitment two to three times faster in China.25

3. Operations cost roughly a third as much

The cost differential between the United States and China follows from the first two mechanisms and from the price of labor. Direct per-patient cost in Phase 3 runs approximately $69,000 in the United States against roughly $25,000 in China.25 At the program level, a Phase 3 oncology study costing $40–50 million in the United States runs an estimated $15–20 million in China, with investigator fees, site operations and enrollment costs at roughly 30–60% of Western rates.24

The composition of that gap matters more than its size. It is not only a discount on scientific procedures: imaging, laboratory assays, and investigational product given China conducts these studies under the ICH E6 good clinical practice standards required for FDA submission.26 The differential concentrates in the operational lines examined later in this paper: monitoring visits, study coordinator and data-management time, site administration, and the per-visit overhead charged by institutions. In other words, the two countries pay similar prices to generate evidence and radically different prices to coordinate and operate the process of generating it (Figure 5).

FIGURE 5: How China Wins: Startup, Enrollment, Cost

Top: elapsed calendar days from regulatory application to first patient enrolled, decomposed into the regulatory review itself and everything that follows. The regulatory clock is not the American constraint: an FDA IND takes effect in 30 calendar days, while China's implied approval runs 60 working days (roughly 84 calendar days). Both comparisons exclude the pre-application period, which averages a further 380 days in the United States and has no direct Chinese analogue. Sources: NMPA Announcements No. 50 (2018) and No. 86 (2025); HHS, Operation TrialBlazer, 2026; WCG and NCI site-activation data; DIA analysis of clinical trial growth in China; industry cost analyses, 2025–2026.

Speed and cost then compound. A program that runs roughly twice as long at roughly two and a half times the cost does not consume twice the capital; it consumes capital at a higher rate for longer, and it does so while a competitor's equivalent asset is accumulating data and approaching an inflection point. For a biotech whose financing is gated on readouts, the relevant quantity is not the study budget but the capital consumed per milestone reached. On that measure the gap is wider than any single line item suggests.

Two qualifications are necessary. First, the arbitrage is being competed away at the top of the market: average upfront payments for China-originated assets have risen sharply as Western buyers have bid against one another, and the discount on the most sought-after programs is narrowing.17 Second, and more consequentially for trial design, a cost advantage realized entirely within one jurisdiction does not automatically transfer to a global registration package. Regulators scrutinize single-country data for applicability to their own populations, which is why the prevailing structure is a multiregional trial with a substantial China component rather than a China-only study. The practical effect is that sponsors capture much of the operational saving while still incurring the cost of Western sites — an arrangement that lowers the blended cost without eliminating the American operational premium.

China treated startup, enrollment, and operations as engineering problems worth solving, and spent a decade solving them with a focus and precision that reset the development timeline. The United States, over the same decade, treated those same problems as unavoidable friction.

VII. The Economic Case

The economic case for a pharmaceutical buyer is more interesting than the price tag alone suggests. Chinese assets do command lower upfronts, with 60 to 70 percent lower and total deal values 40 to 50 percent smaller than comparable Western programs. While the price is the visible part of the transaction, it is not likely the most important driver of the strategic decision. Large pharmaceutical companies are not capital-constrained. They are time-constrained, and time is what a Chinese asset actually delivers.

Consider what a buyer is purchasing. In drug development, absolute cost matters far less than cost measured against market upside, and market upside is governed almost entirely by when a medicine reaches patients. A compound's commercial life is bounded at the far end by patent expiry, so every month spent in development is a month subtracted from the exclusive period that follows approval. For a successful medicine, a year of development time saved converts largely into a year of additional exclusive commercial life at the other end — worth, for a program of any consequence, far more than the entire cost of the trial that produced it. Development savings are measured in tens of millions. Time savings are measured in billions.

Speed compounds a second time through the cost of capital. Drug development is best understood as a race for evidence, in which each milestone cleared converts uncertainty into information, lowers the risk-adjusted discount applied to the program, and unlocks the capital needed to fund the next phase. An asset that reaches human proof of concept in half the time has not merely spent less money; it has become financeable sooner, on better terms, with a longer runway of exclusivity ahead of it. In a market where capital is abundant and de-risked assets are scarce, that is the competition that matters — and it is decided on operations, not on chemistry.

The consequence for American biotech is not that its science is being outbid. It is that its clock is. Two companies may hold molecules of identical merit and identical probability of success, and the one that can generate the same evidence in half the time is worth more to an acquirer, cheaper to finance, and bought first. The licensing shift is therefore not a verdict on American discovery. It is a verdict on American development.

VIII. The Structural Vulnerability of the Emerging Biotech

An emerging biotechnology company is exposed to operational cost in a way a large pharmaceutical company is not, for three compounding reasons.

First, it is pre-revenue. The capitalized cost of bringing a medicine to approval runs from a median near $985 million27 to roughly $2.6 billion across a portfolio inclusive of failures,28 against a median pivotal trial cost of about $19 million, with complex indications routinely exceeding $50–100 million.29 A single program consumes capital faster than most such companies can raise it.

Second, its financing is often milestone-gated. Capital arrives in tranches released against data readouts, which means time is not merely expensive but structurally convertible into ownership. A quarter lost to operational drag is a quarter of additional dilution, or an earlier raise at a lower valuation than a cleaner readout would have commanded. These companies do not pay their operational costs in cash alone. They pay in equity and in runway.

Third, and most consequentially, the emerging company generally outsources significant aspects of the clinical development apparatus. Having limited internal clinical operations organization of meaningful scale, it rents the entire machine — monitoring, data management, safety, regulatory operations, project management — from contract research organizations (CROs). Its constraints are therefore structural: lean teams in which individuals cover work distributed across whole departments at a large sponsor; dependence on vendors whose systems the biotech either has limited visibility into or must manually stitch together; limited headcount leverage, because a fixed runway forecloses hiring one's way out of drag; and no tolerance for delay, because a slipped timeline poses an existential threat.

IX. Where the Capital Actually Goes

Let’s look at where the biotech’s dollars go in clinical development. The activities that actually generate evidence, per-patient clinical procedures and central laboratory work, account for roughly 30% of spend. The remaining 70% funds the complex coordination that currently defines clinical trials.

In the canonical federal cost-driver analysis, administrative and project staff consume 11–29% of trial expenditure and site monitoring a further 9–14%.30 Source-data verification, the practice of dispatching a person to a clinical site to confirm that values in a database match values on a source record, can absorb up to a quarter of a study's total budget.31 Data collection and management, site management and retention, recruitment contracting, and regulatory and document handling account for most of the rest (Figure 6).

FIGURE 6: Where the Clinical Development Budget Goes

Representative allocation of a late-phase development budget based on published cost-component analyses. Approximately 70% of spend funds coordination and operations rather than evidence generation. Sources: Sertkaya et al., Clinical Trials, 2016; HHS; Applied Clinical Trials; industry budget analyses, 2023–2026.

The decisive observation is not the magnitude of this coordination spend but its content. Very little of it is scientific or medical judgment. The prevailing activity of the clinical workforce is reconciliation: people bridging software systems that do not communicate, re-keying values between platforms, chasing and resolving queries, verifying entries against source documents, filing and classifying records, and coordinating handoffs across a vendor stack never designed as a coherent whole. The workforce exists in substantial part to compensate for the fragmentation of the tooling.

It is worth stating plainly what this means for the people doing the work. They are nurses, pharmacists, scientists, and data professionals — among the most capable people in medicine — and a large fraction of their working lives is spent confirming that one system agrees with another. That is not a failure of the workforce. It is a failure of the operating model that employs it.

X. An Industry That Sells Hours

This work has been progressively outsourced for three decades, a process the industry has described as efficiency. Contract research organizations grew from approximately 4% of pharmaceutical R&D spending in the early 1990s to roughly half by the mid-2000s,32 and today constitute a global market of $80–90 billion, roughly three-quarters of it clinical, with monitoring as its single largest service line.33 Clinical outsourcing penetration reached approximately 50% by 2020,34 and the top ten providers capture the majority of that spend.35

It is worth naming what this market is. It is not, in economic structure, a technology industry. It is a labor market with a billing department. Its dominant commercial models make the point plainly: full-service outsourcing prices a bundle of staffed activity, while the functional service provider model dispenses with the abstraction altogether and rents personnel by the hour, at roughly half the margin.36 Revenue scales with headcount deployed and hours consumed.

The organizations best positioned to eliminate clinical coordination work are the organizations whose revenue is that work.

This is not an accusation of bad faith; it is an observation about incentives. An industry that bills hours cannot be the primary agent of a transition whose entire purpose is to eliminate hours. Sponsors expecting their vendors to lead this change are expecting a supplier to compress its own revenue base voluntarily, and should calibrate accordingly.

XI. Two Biotechs, Similar Compound, Wildly Different Outcomes

Suppose two companies hold similar molecules against the same target, with comparable preclinical packages, and file to begin first-in-human studies in the same month. One is in Boston, one in Shanghai. Fourteen months later, the Shanghai company has a human efficacy signal and the Boston company has a protocol and a waiting list.

The direct saving on the Phase 1 study is about two million dollars, which is close to irrelevant. The consequential number is the twenty-two million dollars of additional capital the Boston company consumes to arrive at the same result, and the composition of that number is the whole argument of this paper: it is not principally a discount on procedures or on assays, which cost roughly what they cost anywhere. It is the cost of paying for an entire organization — its people, its facilities and its vendors — for fourteen additional months. The Boston company is not buying more science for its money. It is renting time.

Now consider what a pharmaceutical buyer sees in month fourteen. One asset has human data; the other has a promise. That is not a choice between two prices, and no discount on an upfront payment reverses it. And the fourteen months are not merely returned to the buyer as earlier revenue. They are returned at the far end of the patent term, as additional exclusive commercial life. For a medicine reaching a billion dollars in peak annual sales, an increment of that size is worth on the order of a billion dollars in gross revenue, set against a Phase 1 saving of two million. The ratio is roughly five hundred to one, and it explains a licensing market that cost discipline alone cannot.

The consequence for the Boston company is measured in ownership. Twenty-two million dollars raised before a value-inflection point, at a pre-proof-of-concept valuation, is a materially larger share of the company sold to reach the same milestone. Its investors own less of the same molecule, and they own it later. Compounded across a portfolio and across a decade, that is what the migration of origination actually looks like from the inside. None of this reflects a difference in the quality of the science. In this example the science is identical by construction (Table 1).

TABLE 1: The Same Molecule, Two Development Systems
The Same Molecule, Two Development Systems
From regulatory application to human proof of concept Boston Shanghai
Application to first patient enrolled 10.2 months 5.5 months
Phase 1 conduct 17 months 7 months
Elapsed time to first human efficacy signal 27 months 13 months
Direct cost of the Phase 1 study ~$4M ~$2M
Total capital consumed to reach the milestone ~$41M ~$19M

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XII. Where This Leaves Us

The account to this point is a diagnosis, and it is worth stating in one place. American biotechnology has not lost its scientific advantage. It has lost its operational one. The molecules originated here are as good as the molecules originated anywhere, and in many categories they are better. What differs is the machine that carries a molecule into humans: roughly 380 days between a pre-IND meeting request and an IND submission, a median of 9.4 months to activate a clinical site, contract and budget negotiations measured in tens of weeks, and a clinical workforce whose largest single activity is confirming that one system agrees with another.

That machine is expensive in a specific and correctable way. Approximately 70% of a development budget funds coordination rather than evidence, and almost none of that coordination is scientific or medical judgment. The cost is also compounding rather than additive, because every month the machine adds is a month of capital consumed before a value-inflection point and a month subtracted from the exclusive commercial life of the medicine at the other end. For an emerging company financed against readouts, that is paid in ownership rather than in cash.

The diagnosis carries an implication the industry has been slow to accept. If the American disadvantage were scientific, the remedy would be a generation of new discoveries. It is not scientific. It is verification, reconciliation, documentation, and status propagation performed by people because the software could not close the loop. Software can now close the loop. Part 2 sets out what a clinical development system built on that premise looks like: how the labor model changes line by line, what it costs to reach the same milestone, how the same infrastructure addresses an enrollment problem that capital efficiency alone does not solve, and what regulatory discipline it demands. The question is no longer whether the American development machine can be rebuilt. It is whether it is rebuilt before the trend line in Figure 2 becomes the structure of the market.

XIII. References

1. Hughes SS. Genentech: The Beginnings of Biotech. University of Chicago Press; 2011.

2. Cohen SN, Chang ACY, Boyer HW, Helling RB. Construction of biologically functional bacterial plasmids in vitro. Proc Natl Acad Sci USA. 1973;70(11):3240–3244. doi:10.1073/pnas.70.11.3240.

3. Goeddel DV, Kleid DG, Bolivar F, et al. Expression in Escherichia coli of chemically synthesized genes for human insulin. Proc Natl Acad Sci USA. 1979;76(1):106–110. doi:10.1073/pnas.76.1.106.

4. IQVIA Institute. Global Trends in R&D 2025 and 2026; and Emerging Biopharma's Contribution to Innovation, 2025. (Emerging-biopharma origination and trial-start shares.)

5. IQVIA Institute data via Torreya. Pipeline share by company class, 2002–2022.

6. Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025;75(1):10–45. doi:10.3322/caac.21871.

7. Trickey A, May MT, Vehreschild JJ, et al. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV. 2017;4(8):e349–e356; and CDC mortality data on HIV as a leading cause of death, 1990s.

8. Kang S-Y, et al. Geographic shifts in early-stage biopharmaceutical innovation, 2015–2024. JAMA. 2026. doi:10.1001/jama.2026.1962. (Georgetown University.)

9. GlobalData / Deallus. Global clinical trial initiation share analysis, H1 2026 outlook.

10. Cure Innovation Index. Reagan-Udall Foundation; June 2026. (Trial-start share; discovery-to-IND cycle times; Phase 1 cost differentials.)

11. Citeline Pharmaprojects. Annual R&D review, 2025–2026. (Sponsor rankings; first-launch country analysis.)

12. Nature Reviews Drug Discovery / PitchBook analyses of next-generation antibody trial registration and Chinese IND submissions, 2019–2023.

13. Barwick PJ, Xia M, Xia Y. From Free Rider to Innovator: The Rise of China's Pharmaceutical Industry. NBER Working Paper; 2026. (Stanford SCCEI summary.)

14. European Federation of Pharmaceutical Industries and Associations. W.A.I.T. Indicator Survey (with IQVIA); and national manufacturer-association analyses of patient access delays to newly approved medicines.

15. PharmCube NextBiopharm, via Reuters. China cross-border out-licensing deal value and volume, 2021–2025.

16. Vision Life Sciences. China Out-Licensing Report 2026.

17. Industry deal analyses on China's share of global out-licensing value and comparative deal economics, 2023–2026.

18. Company disclosures: GSK–Jiangsu Hengrui (COPD, 2025); Pfizer–3SBio (SSGJ-707, 2025).

19. Analyses of U.S. pharmaceutical in-licensing from Chinese developers and projected share of future FDA approvals, 2020–2026.

20. GlobalData. Comparative clinical trial duration and cost analyses, China versus United States, 2023–2026.

21. National Medical Products Administration (China). Announcement No. 50 (2018), implied approval of clinical trial applications within 60 working days; and Announcement No. 86 (2025), 30-working-day expedited review pathway for Class 1 innovative drugs, including the twelve-week trial-initiation commitment.

22. U.S. Department of Health and Human Services. Operation TrialBlazer: Roadmap to Maintaining U.S. Leadership in Clinical Research. 2026.

23. WCG site-activation benchmarking, Phase I–III, academic medical centers and hospitals; National Cancer Institute site-activation targets and observed times at NCI-designated cancer centers, 2024; and published multi-site analyses of clinical trial agreement and budget negotiation duration.

24. Analyses of Chinese Grade-3A tertiary hospital trial infrastructure, site concentration, and comparative trial-competition dynamics in developed markets, 2025–2026.

25. Drug Information Association analyses of clinical trial growth in China, including comparative newly diagnosed immuno-oncology populations, per-patient Phase 3 direct costs, and recruitment velocity.

26. International Council for Harmonisation. ICH E6(R3) Good Clinical Practice. See also DIA Trial Master File Reference Model v3.3.1.

27. Wouters OJ, McKee M, Luyten J. Estimated research and development investment needed to bring a new medicine to market, 2009–2018. JAMA. 2020;323(9):844–853.

28. DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ. 2016;47:20–33.

29. Moore TJ, Zhang H, Anderson G, Alexander GC. Estimated costs of pivotal trials for novel therapeutic agents approved by the US Food and Drug Administration, 2015–2016. JAMA Intern Med. 2018;178(11):1451–1457.

30. Sertkaya A, Wong H-H, Jessup A, Beleche T. Key cost drivers of pharmaceutical clinical trials in the United States. Clin Trials. 2016;13(2):117–126.

31. Applied Clinical Trials; industry budget analyses on source-data verification as a share of trial cost, 2023–2026.

32. Analyses of CRO share of pharmaceutical R&D spending, 1990–2010.

33. Grand View Research; Precedence Research; MarketsandMarkets; Fortune Business Insights. Global CRO market sizing and segmentation, 2025–2026.

34. Credit Suisse clinical outsourcing penetration analyses, 2015–2020.

35. Tufts Center for the Study of Drug Development. CRO market concentration analyses.

36. CRO commercial model analyses: full-service outsourcing versus functional service provider economics and margin structure.

ABOUT THE AUTHOR
Michelle Longmire, MD, is a physician-scientist and the co-founder and CEO of Medable, a clinical trial technology company building agentic AI systems for clinical development. Dr. Longmire is a Stanford-trained board-certified dermatologist and author of numerous peer-reviewed publications. Her work spans entrepreneurship, translational science, and clinical research.