Talk to us

Where trial timelines are first lost

Clinical trial site activation now takes months longer than the plans that depend on it, as feasibility, contracts, budgets and ethics reviews pass between sponsors, CROs and sites. Leading sponsors are managing study start-up as a set of priced obligations, each with an owner and a deadline.

Clinical researchSegeta Insights
Clinical research
The number$$856K

a day of delay on a Phase III program

What is at stake

Each month that start-up pushes first patient in can defer about $$25.7 million of value on a composite Phase III program.

Where days are lost
  1. Feasibility to site selection
  2. Contract and budget negotiation
  3. Ethics and regulatory review to greenlight

Clinical trial timelines are usually modeled from first patient in, because enrollment is the variable that sponsors, CROs and investors watch most closely. Yet the months before that date, spent on feasibility, site selection, contracts, budgets, ethics approvals and training, set the start date that every later milestone inherits, from last patient in to database lock and submission. The earlier articles in this series traced how value leaks when a patient passes between clinical teams, and study start-up shows the same handoff problem between sponsors, CROs and research sites.

Each site is activated through a chain of approvals held by different organizations, and the chain is slowest where it is repeated site by site. In registrational oncology trials run from 2020 to 2025, US sites were activated a median of 124 days after final protocol approval, against 308 days outside the US, yet activating 75 percent of planned US sites took a further 309 days, compared with 34 to 126 days in other regions.1 The sections that follow trace where clinical trial site activation loses those days, what each day costs a Phase III program and which actions clinical operations leaders can take now.

Study start-up has lengthened as trials move offshore

Start-up time has grown as protocols, vendors and review steps have multiplied. Tufts CSDD data cited by IQVIA show that the average time from protocol approval to the first patient visit rose 45 percent between 2015 and 2021, while the number of standard vendors per trial rose 61 percent between 2018 and 2023.2 Sites report the strain directly: in an ICON survey of just over 100 investigators and senior site staff, 55 percent said full activation took more than five months from site selection, 39 percent said activation took longer than two years earlier and 66 percent reported frequent contract and budget delays.3

The gap between practice and stated targets is wide. Verily, citing ACRP, puts the average site initiation time for Phase I to III trials at academic medical centers and hospitals at 9.4 months, against a National Cancer Institute target of 90 days.4 Slow scaling has a visible consequence for US research capacity, because 80 percent of patients in the 2025 registrational trials behind novel FDA cancer drug approvals were enrolled outside the US.1

Clinical trial site activation loses days at three handoffs

Every activated site is the product of three handoffs, each owned by a different organization and recorded in a different system: the sponsor's CTMS, the CRO's start-up tracker, the site's contracts office and the IRB portal. Sponsors in the Friends of Cancer Research survey named prolonged budget negotiations, redundant local review and limited site resources as the main causes of slow US activation.1

Even with one standard contract template, negotiation took 41 to 151 days across six multicenter studies.

Exhibit 1One contract template, six studies: negotiation took 41 to 151 daysMedian days to negotiate the FDP-CTSA trial agreement, six Trial Innovation Network studies
Study A41
Study B46
Study C46
Study D64
Study E109
Study F151

Source: Lawrence et al., Journal of Clinical and Translational Science, 2023

01Feasibility to site selection

Sponsors and CROs send feasibility questionnaires that coordinators complete by hand, often repeating answers already held in earlier surveys and the site's own records. ICON reports that site pre-selection decline rates for pharmaceutical and biotech studies rose from 35 percent to 47 percent between 2021 and 2023, so each declined site restarts part of the selection cycle.3

02Contract and budget negotiation

CTA negotiation runs through redlines exchanged by email between the sponsor or CRO, the site's contracts office and its coverage analysis team, and each round waits in someone's queue. The CTSA Contracts Processing Study found average negotiation times above 100 days, and the Accelerated Clinical Trial Agreement saved an average of 55 days across 122 uses at seven sites.5

03Ethics and regulatory review to greenlight

IRB approval, the regulatory binder, investigator training, the site initiation visit and access to IRT and EDC must all close before a CRA can greenlight the site. In nine cardiovascular trials, sites using a central IRB reached first patient enrolled in a median of 199 days against 287 days at other sites, a gap of almost three months that reflects the sequence of review.6

Connected start-up manages each site as a set of obligations

Leading sponsors and CROs are beginning to treat each site's activation as a set of obligations, each with an owner, a deadline and a cost for every day it stays open. A live layer reads the systems already in use, including CTMS, eTMF, the contract repository, IRB portals, email and site messaging, and links every document and redline to the site and milestone it gates. It runs the same four-step loop that the earlier articles in this series describe:

  1. Detect

    a stalled item on the day it stops moving, such as a budget counteroffer that has waited eight business days in a site's queue.

  2. Explain

    which site, enrollment forecast and country milestone the item affects, with the redline history and the person who holds it.

  3. Recommend

    a path to closure, such as approving a fallback clause, escalating to the site's contracts director or shifting forecast enrollment to a backup site.

  4. Execute and track

    each agreed action until the site is greenlit, measuring the days recovered against the start-up plan.

The same record can give sites one channel for feasibility answers, contract status and document requests, replacing many of the parallel email threads that each CRA and contract analyst keeps today. Artificial intelligence does the reading, comparing and drafting, from pre-filling feasibility answers to summarizing redlines against the sponsor's fallback positions, while the clinical operations lead, the contracts manager and the investigator remain accountable for every commercial, ethical and clinical decision.

A day of delay on a Phase III program can cost about $$856,000

Cost of delay in clinical development is the daily value lost when a trial milestone slips, combining the direct cost of running the trial with prescription sales deferred or lost as approval moves later.

Each month that start-up pushes first patient in can defer about $$25.7 million of value on a composite Phase III program.

Exhibit 2. Estimated daily cost of delay for a composite Phase III study

ComponentBasisEstimate per day
Direct trial operating costTufts CSDD mean direct daily cost of a Phase III trial, 2023 dollars 7About $$55,700
Prescription sales deferred or lostTufts CSDD estimate of sales lost per day of delay, 2023 dollars; assumes the start-up slip passes through to approval 7About $$800,000
Total daily exposureSum of the two componentsAbout $$856,000

Source: Segeta estimate based on Tufts Center for the Study of Drug Development data; assumptions are illustrative.

On these assumptions, a 30-day slip in first patient in costs about $$1.7 million in direct trial costs and about $$25.7 million in total, and a 60-day slip about $$51.4 million in total. Part of that exposure can be recovered, because faster enrollment at activated sites or parallel work later in the program may absorb some of the slip, and the sales component applies only if the drug reaches approval. The direct cost sets a floor on the exposure, and for a Phase II study it falls to about $$23,700 a day.7

What clinical operations leaders can do now

  1. 01Plan the study from protocol approval

    Set start-up milestones for every country and site with the same rigor as enrollment targets, and report variance against them each week.

  2. 02Price each start-up obligation per day

    Attach the daily cost of the study to every open contract, budget and ethics item, so a stalled redline is escalated in dollars on the day it stalls.

  3. 03Standardize contracts and budgets before feasibility

    Agree template language, fallback positions and fair market value budget ranges in advance, drawing on agreements such as the ACTA where sites accept them.

  4. 04Run ethics review and contracting in parallel

    Use central IRBs where institutions allow and open contract and budget work as soon as a site is shortlisted, so review and negotiation overlap at every site.

  5. 05Measure the time from signal to action

    Report how many days pass between a stalled item and the assignment of a recovery action, by site, CRO and country.

Sponsors cannot rewrite institutional review requirements or site staffing on their own, yet they can control how quickly a stalled obligation reaches the person who can close it. Those that run study start-up from one live record shared with CROs and sites are likely to reach first patient in sooner, and they may find that the strongest sites choose their studies first.

Questions leaders ask

How long does clinical trial site activation take?

It varies widely by country and site type. In registrational oncology trials run from 2020 to 2025, US sites were first activated a median of 124 days after final protocol approval, against 308 days outside the US, yet activating 75 percent of planned US sites took a further 309 days. Verily, citing ACRP, puts the average at academic centers at 9.4 months.

Why do clinical trial agreements take so long to negotiate?

Each CTA passes through redlines between the sponsor or CRO, the site's contracts office and its coverage analysis team, and every round waits in a separate queue. A CTSA study found average negotiation times above 100 days. Standard templates such as the Accelerated Clinical Trial Agreement saved an average of 55 days across 122 uses at seven sites.

What does a day of clinical trial delay cost?

Tufts CSDD estimates that a day of delay is worth about $$800,000 in lost prescription sales, in 2023 dollars. Direct trial costs add $$7,829 a day in Phase I, $$23,737 in Phase II and $$55,716 in Phase III. On those figures, a composite Phase III study could lose about $$856,000 for each day that approval moves later.

How can sponsors speed up study start-up?

Sponsors can plan from protocol approval, standardize contract and budget templates before feasibility, use central IRBs where institutions allow and run ethics review and contracting in parallel. Managing each site's start-up items as obligations with an owner, a deadline and a daily cost helps a stalled redline or missing document reach the person who can close it sooner.

Notes and sources
  1. Friends of Cancer Research, "Data-driven insights: Fast to start, slow to scale: U.S. oncology trial start-up in a global context," July 2026, friendsofcancerresearch.org.
  2. IQVIA, "Study start-up: Accelerating site activation," white paper citing Tufts CSDD data and the IQVIA Site Survey, April 2024, iqvia.com.
  3. ICON plc, "ICON survey reveals increasing clinical trial startup delays, underscoring need for human-centred site activation solutions," Business Wire, December 2025, businesswire.com.
  4. Verily, "Accelerating study activation for clinical research sites," Perspectives, February 2026, citing ACRP, verily.com.
  5. Colleen E. Lawrence et al., "Quantitative assessment of the impact of standard agreement templates on multisite clinical trial start up time," Journal of Clinical and Translational Science, September 2023, cambridge.org.
  6. Deepak L. Bhatt, "Reconfiguring the cardiovascular clinical trial enterprise in the United States," invited commentary on Goyal et al., JAMA Network Open, July 2021, jamanetwork.com.
  7. Zachary Smith, Joseph A. DiMasi and Kenneth Getz, "Quantifying the value of a day of delay in drug development," Tufts Center for the Study of Drug Development, August 2024, csdd.tufts.edu.