Clinical Study Protocol Writing for Trial Sponsors
Pubrica writes clinical study protocols, synopses and amendments for trial sponsors. Our regulatory medical writers prepare sponsor protocols to the ICH M11 structure. Most of a trial’s cost is determined in the protocol: Phase II protocols now average 3.3 substantial amendments and Phase III 3.5, and each takes a median of 260 days from identifying the need to final ethics approval. We test the eligibility criteria against the population they exclude and define the estimand before data collection begins.
- ICH M11 structure, adopted at Step 4 in November 2025; most protocols in circulation still predate this harmonised template
- Eligibility criteria tested against the population each one excludes, because criteria are often carried over from earlier protocols, and under-enrolment is the largest non-scientific reason for trial termination
- Critical-to-quality factors identified under ICH E8(R1), so that procedures are prioritised by their importance to the trial’s objectives
- The estimand defined before the schedule of assessments under E9(R1), so that the endpoints and the analysis address the same question
- Amendments drafted with a clear change-impact assessment, setting out the affected sections, re-consent implications and ethics rationale for the committee
Full protocol and synopsisIncluded
Amendments and change-impact documentationIncluded
Eligibility and endpoint reviewIncluded
Schedule of assessments rationalisedIncluded
Sponsor approval and ethics submissionYour responsibility
Concept → scoped → drafted → risk-checked → protocol
- ICH M11 structure
- Criteria tested against recruitment
- Critical-to-quality factors identified
- Estimand defined before the schedule
- Amendment risk checked before submission
Deliverables
Four Deliverables Included in Every Clinical Study Protocol
Each protocol addresses one question, one population and one primary endpoint. What the study is powered to establish determines which procedures the schedule can justify.
From the feasibility check18 criteria, six carried from a previous study.Four criteria excluded 61% of the eligible population between them, and two of the four related to a question this study was not asking. The revised protocol has thirteen criteria and the same scientific scope.
From the schedule reviewTufts analysis published in December 2025 found roughly a third of Phase III procedures non-core, carrying 25 to 30 per cent of the burden on participants and sites — and Phase III protocols now collect an average of 5.9 million datapoints.
From the endpoints sectionMissing data will be handled using last observation carried forward.Treatment policy estimand; discontinuation and rescue medication named as intercurrent events with their handling strategies stated; sensitivity analyses specified.
From the amendmentOn a typical substantial amendment, sites run under different protocol versions simultaneously for an average of 215 days, and two-thirds of participants are re-consented. A clearly written amendment helps reduce the first figure.
All samples are illustrative and anonymised. Hover over a sample to replay it.
Compliance and Standards
Four Regulatory References for Clinical Study Protocols
Where your sponsor template or regulatory agency has stated a position, we follow it.
Structured protocol template (Step 4, November 2025)
The harmonised protocol content and technical specification, known as CeSHarP. TransCelerate has realigned its Common Protocol Template to it; most templates still in circulation predate it.
Good Clinical Practice (E6(R3), not E6(R2))
Annex 1 took effect in the EU in July 2025; Annex 2, covering pragmatic and decentralised designs, follows in January 2027.
Statistical principles with estimands (E9(R1), 2019)
Defines the estimand framework. Citing E9 alone is incomplete, because the addendum governs how intercurrent events are defined and handled.
General considerations for clinical studies (Step 4, October 2021)
Quality by design and critical-to-quality factors — the basis for deciding which procedures are core and which are burden.
Responsible Use of AI
Responsible Use of AI in Regulatory Writing
Regulatory reviewers trace each decision back to evidence and to a responsible individual. Our specialists therefore treat source traceability as more important than speed, and every statement in a document must be supported by a traceable source.
Why We Do Not Publish AI Accuracy Figures
Accuracy figures for AI tools are usually reported by the companies that sell them.
For this reason, Pubrica does not quote an accuracy figure of its own, as it would carry the same conflict of interest. We tell you which tool was used on your project, at which stage, and what a specialist changed afterwards.
Methodology
How Our Clinical Study Protocol Writing Process Works
We review the study design before drafting begins, because a protocol drafted directly from a concept sheet carries forward any assumptions that have not been examined.
Design review and scoping
We examine the question, population, endpoints and their estimands, the comparator and the proposed schedule against what the study is powered to show.
Eligibility and schedule rationalisation
We test each criterion against the population it excludes and trace each procedure to an objective, removing those that do not map to one. This step helps avoid later amendments.
Drafting to ICH M11
The protocol is written to the harmonised structure, with the statistical section aligned to the SAP and the risk information aligned to the investigator’s brochure.
Amendment risk check
Before the protocol goes to the ethics committee, we review it for issues that commonly lead to amendments.
Our Experts
Our Clinical Study Protocol Writing Team
The same named team of regulatory specialists works on your project from scoping to delivery, and your project coordinator introduces each member before work begins.
Writes the document against the governing template and regulatory guidance, keeps every statement traceable to its source data, and maintains the version history and comment log through each review round.
Reviews the clinical and scientific content for accuracy and confirms that each conclusion is supported by the data. The expert is matched to your therapeutic or device area.
Checks that statistical methods, tables and conclusions are consistent with the analysis plan, and reviews how the data are presented before the document reaches regulatory review.
Performs an independent check of the final document against source data, the template and the applicable regulatory checklist. Findings are logged and resolved before delivery.
Packages
Two Clinical Study Protocol Service Options, Quoted per Project
Cost depends on the trial phase, indication, design complexity and whether an existing synopsis or concept is available.
Protocol and synopsis
Sponsors writing a new study protocol
Quoted per projectOn phase and design complexity
Delivery By scope
- ✓Full protocol to ICH M11 structure, with synopsis
- ✓Eligibility criteria tested against recruitment
- ✓Schedule of assessments rationalised against objectives
- ✓Estimand framed under E9(R1)
- ✓Aligned with the SAP and the brochure
- ✓Amendment risk check before submission
Device studies are written to ISO 14155:2026 rather than to ICH E6 alone.
Deliverables Request a quoteProtocol amendment
Studies already running
Quoted per projectOn the scale of the change
Delivery By scope
- ✓Amendment drafted with rationale and affected sections
- ✓Change impact on analysis and endpoints assessed
- ✓Re-consent implication stated for the committee
- ✓Substantial versus non-substantial position argued
- ✓Consistency re-checked across protocol, ICF and brochure
Clear amendments are approved more quickly, which reduces the time sites spend working under different protocol versions.
Deliverables Request a quoteSend us your draft protocol and we will carry out a free amendment risk check, identifying eligibility criteria likely to limit recruitment, endpoints without a matching estimand and procedures that do not map to an objective. The check takes five business days.
FAQs
Clinical Study Protocol FAQs
If your question is not answered here, ask an expert. No quote is required.
M11 is the harmonised structured protocol template, adopted at Step 4 on 19 November 2025, together with a technical specification. TransCelerate has realigned its Common Protocol Template to it.
It is not yet mandatory in every region, but it is becoming the standard, and most templates in circulation predate it. Writing to M11 now avoids restructuring later and allows the protocol to map clearly onto the study report.
We test the two areas that cause most amendments before submission: the eligibility criteria against the population each one excludes, and the schedule of assessments against the objectives each procedure supports.
The 2016 Tufts analysis found 45 per cent of amendments avoidable, and more recent data show the number of amendments rising. A design review costs far less than an amendment.
No. A research proposal supports an investigator seeking funding or ethics approval for their own study, whereas a sponsor protocol governs a trial that a regulator may later review.
The two documents differ in purpose, audience and standards. We provide investigator-initiated protocol and proposal writing through our physician writing services.
Yes. It should be written together with the statistical analysis plan, and the estimand should be stated in the same way in both documents.
Where the protocol and the SAP describe the analysis differently, the difference appears in the study report and must be explained in section 9.8.
Yes. Clinical investigation plans for devices are written to ISO 14155:2026, EU MDR and 21 CFR 812 rather than to ICH E6 alone.
Please note that ISO 14155:2020 has been withdrawn and was replaced by the fourth edition on 23 March 2026, so any device template written before that date should be checked.
Related Services
Related Clinical Trial Writing Services
The protocol governs all later trial documents and must be consistent with the documents written alongside it.
1COMPANION DOCUMENTSkept consistent with the protocol
Investigator's brochureSafety and clinical data for investigators. Informed consent formTrial risks explained for participants.2TRIAL DOCUMENTATIONdocumentation and disclosure
Clinical trial supportSAP, registry records and CSR. Experimental designDesign, endpoints and sample size.3TRIAL REPORTINGreporting against the protocol
Clinical study reportTo ICH E3, including section 9.8. BiostatisticsAnalysis against the pre-specified plan.Request a Free Amendment Risk Check of Your Draft Protocol
We identify eligibility criteria likely to limit recruitment, endpoints without a matching estimand and procedures that do not map to an objective. The check is free and takes five business days.