A 2026 ACRP analysis of nine cardiovascular trials found median regulatory approval took 78 days with a central IRB versus 165 days with a local IRB, with total start-up stretching to 199 versus 287 days. That's more than four months of difference before a single patient is enrolled.
This article breaks down where these delays actually come from and how CROs like DRK Research Solutions build processes to avoid them.
Key Takeaways
- Incomplete dossiers, inconsistent consent documentation, and weak multi-country coordination drive most IRB/EC delays
- ICH E6(R3) proportionate review speeds lower-risk studies when sponsors structure submissions around it
- Early engagement, standardized documentation, and dedicated liaison support prevent avoidable IRB/EC delays
- Multi-regional trials compound delay risk because each country applies its own EC/IRB rules and terminology
What Ethics Committees and IRBs Review Before Approval
In the US, human-subjects ethics review is handled by an Institutional Review Board (IRB), defined under 21 CFR 56.102(g) as a formally designated board that reviews research involving human participants. Internationally, the same role falls to an Independent Ethics Committee (IEC) or Research Ethics Committee (REC). The names differ, but the mandate is the same: protect participant rights and safety.
Core review scope includes:
- The protocol and any amendments
- Informed consent forms and related materials
- Investigator qualifications
- Recruitment materials
- Ongoing safety data
Under 21 CFR 56.108, the IRB can approve, require modifications, or disapprove a study outright. Approval isn't optional or negotiable. No enrollment happens without it. That's exactly why delays at this stage ripple through the entire trial timeline.
The Most Common Causes of Ethics Committee and IRB Delays
Incomplete or Inconsistent Submission Packages
Missing documents, mismatched protocol versions, or numbering inconsistencies across a dossier are the leading reasons submissions bounce back before review even starts. A 2001 multicenter asthma trial across 44 sites shows the scale of the problem: 82% of protocols were returned one to four times for revisions, with an average of 3.5 requested changes per submission. Of those changes, 91% were consent-related, according to a systematic review of empirical IRB literature.
Poorly Written or Non-Compliant Informed Consent Forms
Overly technical language, missing required elements, or forms that haven't been localized for the target population routinely trigger revision requests. In one historical review of a single protocol submitted to 16 IRBs, only 3 consent forms contained every regulatory requirement. Thirteen didn't.
Protocol Design and Risk-Benefit Ambiguity
First-in-human and vulnerable-population studies draw extra scrutiny when risk-benefit justification is unclear. A 2025 survey of US IRB chairs found 66% considered early-phase risk-benefit analysis harder than later-phase review. Only half felt preclinical data gave them enough to assess risk, according to a peer-reviewed survey of US IRB chairs. Weak justification invites follow-up questions that push decisions into later meeting cycles.
Jurisdictional and Terminology Mismatches in Multi-Country Trials
Sponsors unfamiliar with local requirements often submit documents built for the wrong system. The UK's dual HRA/REC process is a clear example: HRA Approval covers governance and legal compliance, while the REC evaluates ethics, all within one application. Sponsors expecting a US-style single-board process can misjudge what's needed.
Delayed Responses to Committee Queries
Slow sponsor or investigator turnaround on requested clarifications is one of the most preventable causes of extended timelines. When a query sits unanswered, the delay belongs to the sponsor or investigator, not the committee.
Lack of Early Engagement or Pre-Submission Consultation
Sponsors who skip informal consultation with committees before formal filing lose the chance to fix issues before they become formal deficiency letters. It's a cheap insurance policy most sponsors underuse.
Additional Complexity in Multi-Regional Clinical Trials
Multi-regional clinical trials (MRCTs) require separate ethics approvals in every participating country, each with its own timeline, quorum rules, and documentation format. ICH E17 guidance confirms that all MRCT sites must meet local quality, ethical, and regulatory standards. Differences such as safety-reporting timelines must be followed locally, not according to a single global template.
This creates a common failure pattern:
- One country's site is approved and ready to enroll
- Another site's consent form translation is still under committee review
- A third site is waiting on a local safety-reporting format that doesn't match the sponsor's global template
Sponsors without in-country regulatory expertise frequently underestimate submission lead times when they build out global trial timelines. The result: one slow ethics approval holds back an entire regional launch.
How CROs Prevent Ethics Committee and IRB Delays
Experienced CROs address these failure points before they become formal rejections.
- Pre-submission gap analyses: reviewing protocols and consent documents against local EC requirements before formal filing catches mismatches early
- Standardized, reusable dossier templates: consistent formatting and version control across countries cuts administrative rejections
- Dedicated regulatory and ethics liaison support: tracking query response deadlines and maintaining direct committee communication so clarifications do not stall
- Proportionate review awareness: ICH E6(R3) encourages a risk-based approach; CROs who know the framework can flag studies that may qualify for expedited review
- Centralized document control: keeping every regional office on the same protocol version reduces mismatched-document errors that trigger resubmissions
DRK Research Solutions operates across Europe, the Middle East, Asia, Africa, and the Americas, with regional leadership based in the UK, USA, Malaysia, and beyond. That localized footprint matters for sponsors running MRCTs.
Navigating a UK REC application looks nothing like a submission process in Southeast Asia or the Middle East. People on the ground who understand local expectations, rather than a single template applied everywhere, keep one difficult site from holding up an entire study.
Best Practices Sponsors Can Adopt to Minimize Delays
Sponsors don't have to wait for a CRO to fix these problems. A few habits go a long way:
- Bring in regulatory and ethics expertise during protocol design, not after the protocol is locked. Fixing risk-benefit language before submission is far cheaper than fixing it after a deficiency letter.
- Build country-specific buffer time into MRCT timelines. Treat each country's EC/IRB process as its own project with its own lead time, not a rounding error on the master schedule.
- Assign one person to own committee query responses. When accountability is diffuse, queries sit in inboxes. When one person owns the tracker, they get answered.
Frequently Asked Questions
What is the role of an ethics committee in clinical trials?
Ethics committees independently review and approve trial protocols, consent forms, and ongoing safety data to protect participant rights and well-being. Their approval is required before any enrollment can begin.
Is an IRB the same as an ethics committee?
Yes, functionally. IRB is the US-specific term, while ethics committee, IEC, or REC are used internationally. Both perform the same core oversight role.
What is the difference between HRA and REC approval?
In the UK, HRA Approval covers governance and legal compliance, while REC review specifically evaluates the ethical aspects of a study. Both are folded into a single application and are required before trial start.
What documents are typically required for an ethics committee submission?
Standard submissions include the protocol, Investigator's Brochure, informed consent forms, investigator qualifications or CVs, and recruitment materials. ICH E6(R3) also expects participant information and safety updates where relevant.
How long does ethics committee or IRB approval typically take?
Timelines vary widely by jurisdiction and study risk level — published figures range from roughly seven weeks to several months. Incomplete submissions remain the most common cause of extended timelines.
How can a CRO help speed up ethics committee approval for a multi-country trial?
CROs with in-country regulatory experience can check submissions against local requirements before filing and manage query responses so committees aren't left waiting. That combination prevents many of the avoidable delays sponsors run into on their own.
