A reviewer asking for “one more experiment” is routine peer-review feedback. But sometimes the request is not a matter of effort — it genuinely cannot be done. The animal cohort has been dispersed. The patient population no longer exists in that form. The equipment was decommissioned. The cost is an order of magnitude beyond what any co-author can fund. The ethics approval would take longer to obtain than the journal’s revision deadline allows. This guide covers how to respond when a reviewer’s requested experiment is infeasible, not merely inconvenient — how to establish that the constraint is real, how to say so in the response letter without sounding evasive, and how to propose a credible alternative that addresses the reviewer’s underlying scientific concern.
This is a narrower problem than reviewer disagreement in general. CASRAI’s guide to writing a response to reviewers letter covers the letter’s overall structure and tone, and the guide to handling conflicting or contradictory reviewer feedback covers what to do when two reviewers want opposite things. Neither addresses the specific situation covered here: a single, well-intentioned request that is simply not executable within the resources, timeline, or ethical approvals available to you. If you’re earlier in the process and unsure what a revision request even obligates you to do, start with CASRAI’s guide to what a revise and resubmit decision means.
Why editors and reviewers ask for experiments that can’t be run
A reviewer’s request is almost never arbitrary, even when it’s impossible for you to fulfill. It is a proxy for a scientific concern: usually “I’m not fully convinced by the evidence you have,” “this claim needs a stronger causal test,” or “the generalizability of your finding is unclear.” Reviewers evaluate a manuscript against an idealized study design, not against your actual remaining budget, IRB timeline, or cohort availability — they typically have no visibility into any of those constraints unless you tell them. This is the starting point for a credible response: the reviewer is very unlikely to abandon their underlying concern just because you say the experiment isn’t possible. You have to address the concern by some other route, not simply decline the request.
Step 1: Confirm the constraint is real, specific, and durable
Before writing anything to the editor, verify precisely why the experiment cannot be run, in terms specific enough to state plainly. Vague framing (“this would be difficult”) reads as reluctance rather than infeasibility and invites a skeptical editor to push back. The common categories, and what makes each one credible:
- Time. The requested experiment (a longer follow-up period, a second recruitment wave, a replication cohort) genuinely cannot be completed within any realistic revision window — state the actual duration required (e.g., a multi-year follow-up interval) against the journal’s typical revision deadline.
- Cost. The experiment requires reagents, instrument time, participant compensation, or specialist assays that exceed remaining grant funds, and there is no funding mechanism available on the relevant timescale. A rough order-of-magnitude figure, even without an exact quote, is more persuasive than an unspecified claim of expense.
- Access. The sample, cohort, site, biospecimen archive, historical dataset, or instrument no longer exists, is no longer accessible to you (a collaborator relationship ended, a biobank’s material was exhausted, a field site is now inaccessible), or was never something you controlled.
- Ethics and regulatory approval. The requested experiment would require a new or amended IRB/IACUC/ethics-committee protocol, additional informed consent, or a new regulatory filing, and that approval process alone exceeds the revision timeline — or the request asks for something an ethics body would not currently approve at all (e.g., additional invasive procedures on a study population, re-contacting participants outside the consented scope).
Several of these can overlap — a repeat animal experiment might be blocked by both cost and a lapsed pilot-cohort’s ethics approval simultaneously. State all of the constraints that genuinely apply; a single-reason explanation that omits a second, equally real reason can look thin if the editor or reviewer probes the first one.
Step 2: Don’t just refuse — address the underlying concern another way
A response that says only “this experiment is not feasible” and stops there is the single most common reason this kind of response fails with an editor. Reviewers and editors are receptive to genuine infeasibility, but only when it’s paired with a serious attempt to close the evidentiary gap by some other means. Work through these options roughly in this order before concluding nothing can be offered:
Reanalyze data you already have
Before proposing any new data collection, check whether the reviewer’s underlying concern can be addressed with additional analysis of existing data: a subgroup analysis, a sensitivity analysis under different assumptions, a different statistical model, or a post hoc power calculation showing what effect size your existing sample could and couldn’t detect. This is frequently the fastest and cheapest route to a credible answer, and it directly demonstrates good faith without requiring any new resources.
Propose a smaller, scoped-down version of the same experiment
A full replication or an extended cohort may be infeasible while a smaller, targeted version that tests the same underlying mechanism is not. If the reviewer wants a dose-response series across ten conditions and you can run three that bracket the range, or a full preregistered multi-site replication where a single-site version is realistic, offer the scaled-down version explicitly rather than leaving the gap between “everything requested” and “nothing” implicit.
Cite existing published evidence
If the requested experiment has effectively already been run — by your own group in prior work, or by an independent group whose published data addresses the same question — cite it directly and explain why it substitutes for new data collection. This is a legitimate and common substitution, provided the cited work genuinely speaks to the reviewer’s specific concern rather than being adjacent to it.
Propose the experiment as future work, with a concrete plan
When none of the above closes the gap, the remaining honest option is to commit to the limitation openly: state explicitly in the manuscript (typically in the discussion or a dedicated limitations subsection) that the requested experiment was not feasible within the constraints of this study, explain the specific constraint, and frame it as a defined direction for future work rather than an unaddressed gap. CASRAI’s worked example of a limitations section shows the register this typically takes. An editor evaluating a revision is assessing whether the paper’s claims are appropriately scoped to the evidence it actually has — an honestly stated limitation, with the claim’s scope narrowed to match, is often a fully acceptable outcome; an unaddressed gap that the paper’s claims quietly ignore is not.
Step 3: Write the response letter entry
Structure the individual point-by-point entry for this comment the same way as any other response-letter entry (see CASRAI’s response-letter guide for the overall format), but make sure this specific entry does three things in order:
- Acknowledge the underlying scientific concern in your own words — showing the reviewer you understood what they were actually asking for, not just the literal instruction.
- State the constraint plainly and specifically — name the category (time, cost, access, ethics/regulatory) and give the concrete reason, not a vague gesture at difficulty. “This experiment would require [specific resource/approval], which is not available within [specific reason: the revision timeline, the current grant period, the now-closed access to the cohort]” reads as a fact, not an excuse.
- Present what you did instead — the reanalysis, the scoped-down experiment, the cited existing evidence, or the added limitation — and point to exactly where it now appears in the revised manuscript (page/section reference).
Avoid two failure modes that read poorly to editors: over-apologizing (multiple sentences of regret before getting to the substance) and under-explaining (a one-line “not feasible” with no reason given). A brief, factual, specific explanation is more persuasive than either.
A general framing template
Adapt to your own case rather than using this verbatim, but the shape holds across most infeasible-experiment situations:
“We agree that [restate the underlying concern] would strengthen this finding, and we considered [the requested experiment] carefully. However, [specific constraint: e.g., the cohort used in this analysis was collected under a protocol that has since closed to further recruitment / this assay requires [instrument/reagent] that is no longer available to our group / an amended ethics approval for this procedure would require approximately [timeframe], beyond what this revision cycle allows]. As an alternative, we [reanalyzed the existing data using X / conducted a smaller version of the requested experiment testing Y / cite prior work by Z that addresses the same question], which we believe addresses the reviewer’s concern to the extent currently possible. We have also added a statement to the discussion (page/line) noting this as a limitation and a direction for future work.”
When the editor pushes back anyway
Occasionally an editor sides with the reviewer and treats the requested experiment as a condition of acceptance rather than a preference. If your constraint is genuinely durable (a closed cohort, an expired approval, a real cost ceiling), a second, more detailed explanation to the editor directly — outside the point-by-point response — is appropriate; the Committee on Publication Ethics’s guidance on handling author-editor disagreement during peer review is the relevant reference point for what a reasonable appeal looks like. If the paper’s central claim genuinely cannot stand without the requested evidence and no substitute is available, the honest outcome may be narrowing the claim rather than the study, not resubmitting to a different, less rigorous venue to avoid the request — that undermines the same evidentiary standard the reviewer was asking about in the first place.
Frequently asked questions
Is “we don’t have funding for this” ever a sufficient reason on its own?
It’s a real and legitimate constraint, but stated alone it is often unpersuasive because reviewers and editors have no way to evaluate it. Pair it with a rough scope of what the experiment would require (the specific reagents, instrument time, participant compensation, or specialist service involved) and, where possible, what alternative evidence you can offer instead. A cost constraint paired with a genuine substitute is far stronger than a cost constraint stated in isolation.
What if the reviewer’s requested experiment is technically possible but would take years?
State the actual timeline required and explain why it exceeds what any revision cycle can accommodate. This is a legitimate time constraint, not evasion, provided the estimate is realistic and specific. Framing the experiment as a defined next step for future work, ideally with a citation to a registered protocol or preprint if one exists, is usually the right resolution.
Should I offer to run a smaller version of the experiment even if it doesn’t fully answer the reviewer’s question?
Generally yes, provided you’re explicit that it’s a partial answer rather than presenting it as equivalent to the full request. A scoped-down experiment that genuinely tests the same mechanism, clearly labeled as such, demonstrates good faith and often satisfies reviewers whose real concern was “no evidence at all” rather than “this exact experimental design.”
Can I just remove the claim the experiment was meant to support instead of running anything new?
Yes, and this is frequently the most honest resolution when no substitute evidence is available: narrow the claim to what your existing data actually supports, and add the requested experiment to the limitations and future-work discussion. This is a legitimate outcome of peer review, not a failure to satisfy the reviewer — reviewers are generally more receptive to an appropriately narrowed claim than to an unaddressed evidentiary gap the manuscript pretends isn’t there.
How is this different from responding to conflicting reviewer feedback?
Conflicting feedback involves two or more reviewers whose requests cannot both be satisfied — the resolution is choosing or synthesizing between them, covered in CASRAI’s guide to conflicting reviewer feedback. An infeasible-experiment request is a single reviewer’s request that cannot be satisfied by any version of the requested experiment at all, regardless of what any other reviewer wants — the resolution is substitution or narrowing, not choosing between competing instructions.
