As we dust ourselves off from 2025, we rub our bleary eyes and 2026 starts to come in to focus. Last year was the start of some of the biggest changes we have seen in over a decade, new guidelines, upcoming standards and the looming impact of AI.
You’ll notice I said “start”, that’s because it is nowhere near finished and this year is poised to be one that will make us laugh, make us cry, celebrate the small wins and prepare for the more to come.
I can’t predict the future, if I could I would be on a private island somewhere enjoying my millions from getting in early on the Pokémon trading card hustle, what I can do though is share with you my thoughts for what 2026 has ready for us, what we should look out for and what you may need to catch up on.
Here are my 6 for 2026 of things to help you get prepared for the next 12 months.
1. TMF Standard Model V1: The Preparation Year
The TMF Reference Model is undergoing its biggest transformation since inception. V3.3.1 will be the final version as we know it, with the newly named TMF Standard Model V1 planned to launch H1 2027. This means 2026 is the year to prepare.
Here’s what makes this different: Record Types (formerly Sub-Artifacts) are now a core part of the structure. If your organisation has been filing documents at the Artifact level only, you might have some work ahead. We’re talking about approximately 2,000+ Record Types in the new version. Before you panic, remember that not every trial uses all 2,000, you’ll use what’s relevant to your study, it is also worth remembering we already have over 600 sub-artifacts, this expansion just reflects the reality of modern clinical trials. From an operational standpoint, 2026 is less about knowing every change coming and more about understanding impact of any change. Sponsors who can objectively assess gaps will be far better positioned to plan for success with resourcing, and inspection readiness.
The TMF Standard Model V1 isn’t just a name change, it’s a shift years in the making. We’re moving from a “model” that recommended interpretation and variation, to a “standard” that provides definitive structure and regulatory alignment.
What should you be doing in 2026:
- Make sure you keep up to date with the quarterly TMF General Meetings hosted by CDISC, this is where all the news will be shared.
- Assess your current TMF structure, are you filing at Record Type level? How different is your structure from the basic?
The vendors are aligned, the community is engaged, and the industry push is there. Question now is will you be ready?
2. ICH E6(R3): From Theory to Reality
ICH E6(R3) reached Step 4 on January 6, 2025. The regulatory dominoes are already falling:
- EMA (Europe): Implemented July 23, 2025
- FDA (US): Published guidance September 2025
- Health Canada: Implementation effective April 1, 2026
- UK MHRA: New guideline effective April 28, 2026
- Japan PMDA: Still in assessment phase
2026 is the year where E6(R3) stops being theoretical and starts being what regulators expect to see.
Health Canada’s announcement is particularly telling. They’re providing a six-month preparatory period for stakeholders to conduct training, revise SOPs, update quality management systems, and align trials with new expectations. They’re making it clear that sponsors need to identify Critical to Quality Factors with associated risks and mitigation measures. This isn’t a suggestion. Beyond SOP updates, sponsors will need to consistently demonstrate, through evidence, that oversight activities are occurring and effective across all delegated activities.
This impacts every aspect of your TMF processes and records: “Participants” instead of “subjects” across all documents, enhanced CRO oversight requirements, risk-based monitoring plans, new data governance documentation, and specific computerised systems validation.
For TMF professionals, this means updates to essential record lists, metadata requirements, quality measures, SOPs, work instructions, and training materials. With Health Canada and MHRA both implementing in Q2 2026, your TMF needs to reflect the new reality.
3. AI Goes Production in the TMF
I’ve been talking about AI for a while, RAG systems, automated test data, Vibe Coding, but 2026 is different. This is the year AI moves from “interesting pilot” to “this is how we work now.”
The AI in clinical trials market grew from $7.73 billion (2024) to $9.17 billion (2025), projected to hit $21.79 billion by 2030.ix Over 50% of major pharmaceutical companies are now “heavy AI users.”
What’s more telling though is what I’ve seen at conferences. The tone has shifted. A year or two ago, AI presentations were met with scepticism. Now? People are sharing real implementation stories, discussing validation strategies, and problem-solving on 21 CFR Part 11 integration.
What’s actually being deployed:
As AI-supported processes move into production, regulators will increasingly expect clear governance models and evidence that these systems are monitored, controlled, and understood by the business.
- Automated document classification using ML models
- NLP for metadata extraction
- AI-powered quality checks identifying missing pages and incorrect filing
- RAG systems for internal SOPs and guidance
- Predictive analytics identifying at-risk documents
The key difference in 2026 is compliance frameworks are catching up. Companies are figuring out how to qualify these systems, maintain oversight, and explain AI-assisted processes to regulators.
If you haven’t started exploring AI tools for your TMF processes, you’re missing out on all the fun.
4. The Site System Crisis: A Problem About to Break
This isn’t a new trend, but it’s still as relevant as ever, clinical trial sites are juggling an obscene amount of systems. Research coordinators spend significant hours on redundant data entry. Combine that with the fact that almost a third of sites report inadequate training on all these systems, it is a recipe for disaster.
All this friction is causing more and more strain on Sponsor, CRO and Site relationships.
It is a bubbling problem that’s going to break. Sites are drowning, and when sites struggle, Essential Record quality suffers. Late submissions, incorrect metadata, poor-quality scans, often these are symptoms of overwhelmed sites in impossibly fragmented technology environments. But more important than of this, patients suffer, and that is a non-negotiable for everyone involved.
Could a ISF Reference Model help ease the pain?
In July 2025, the Investigator Site File (ISF) Reference Model was released for public review. Developed in alignment with TMF Reference Model V3.3.1, it provides standardised framework for site-level documents.
This matters because site documentation chaos directly impacts sponsor TMF quality. The ISF Reference Model, integrating with TMF Standard Model V1, is the industry’s attempt to bring order to site-level documentation.
What needs to happen in 2026:
- Industry push for system integration and interoperability
- ISF Reference Model adoption to reduce site burden
- Technology stack audits, do sites really need 20+2 systems?
- Investment in training that actually works
If we don’t address this, we’ll see increased site refusal rates, higher dropout rates, and continued quality issues that no amount of central review can fix.
5. CRO eTMF Access: Non-Negotiable in 2026
ICH E6(R3) fundamentally shifted Sponsor-CRO dynamics. It provides explicit guidance on CRO selection, ongoing oversight, and what can be delegated. Most importantly: sponsors have the right to access their CRO’s eTMF. This isn’t negotiable anymore, and let’s be honest it might be their eTMF but it has always been the Sponsor’s TMF.
E6(R3) introduced 48 instances of enhanced CRO oversight requirements.12 Your TMF needs to document CRO selection criteria, delegation of responsibilities, ongoing performance monitoring, quality review results, and communication paths.
For many sponsors, 2026 will be contract renewal season. If your CRO contracts don’t include clear eTMF access provisions, they need updating. If your CRO is claiming proprietary reasons for limiting access, E6(R3) has removed that argument.
The practical reality:
Many sponsors operated with “trust but don’t verify.” That model is done. Regulators explicitly look for evidence of sponsor oversight: regular access to CRO eTMF systems, quality review of CRO-managed content, documentation of oversight activities, and clear accountability.
If you’re in CRO selection or contract renewal in 2026, system access should be non-negotiable.
6. Metrics Maturity: From Dashboards to Action
I’ve written about the TMF Trinity, Timeliness, Quality, Completeness. These metrics are almost standards now. But here’s what I’m seeing for 2026: evolution from “we measure these things” to “we use measurements to prevent problems.”
It’s the difference between a thermometer and a thermostat. The organisations seeing the most value are using metrics not just for reporting, but as decision-support tools—prioritising action, focusing resources, and preventing issues before they surface during inspection.
Traditional approach: Monthly reports on TMF health. Red/amber/green status to leadership. React when things go red.
2026 approach: Continuous monitoring with predictive analytics. AI-powered systems identifying patterns before quality issues occur. Automated alerts triggering corrective actions before metrics decline.
- Cross-system integration: The most sophisticated TMF teams aren’t looking at eTMF data in isolation. They’re integrating eTMF metrics with CTMS data, monitoring reports with completeness, training rates with submission quality, and site performance with document timeliness.
- AI-powered analytics: Machine learning now predicts which artifacts are at risk, identifies sites likely to have quality issues, suggests resource allocation, and flags unusual patterns indicating systemic issues.
Final Thoughts
2026 is a year of transition and maturity. It is a year that will test even the best of us, but it’s also a year of immense opportunity. We’re moving from models to standards, pilots to production, theory to practice, reactive to proactive.
What gives me the most hope about all this though is the community, you will never find a better group than those in Clinical Records, they share ideas, discuss pain points openly and lift each other up. There is no us versus them, it’s one for all and all for one
Hopefully this article was helpful, and each item gives you an idea of what work needs doing, changes that need making, and mindsets that need shifting. Organisations treating 2026 as a preparation year; getting ahead of TMF Standard Model V1, implementing E6(R3), deploying AI responsibly, addressing site burden, ensuring CRO oversight, and maturing metrics, will be positioned for success.
2026 is shaping up to be a preparation year. Organisations that take time now to assess readiness, identify gaps, and understand risk will be far better positioned when standards and expectations fully land.
Those that wait will be playing catch-up for years.
References
CDISC. TMF Standard Model v1 Project Webinar.
https://www.cdisc.org/events/webinar/tmf-standard-model-v1-project-webinar
International Council for Harmonisation (ICH). ICH E6(R3) Good Clinical Practice Guideline Reaches Step 4. ICH Official Website, January 6, 2025.
https://www.ich.org/page/efficacy-guidelines
European Medicines Agency. ICH E6(R3) Guideline: Good Clinical Practice (GCP) – Step 5.
https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e6-r3-guideline-good-clinical-practice-gcp-step-5_en.pdf
U.S. Food & Drug Administration. E6(R3) Good Clinical Practice (GCP).
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/e6r3-good-clinical-practice-gcp
Health Canada. Implementation of ICH E6(R3) Guideline – Notice.
https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/announcements/implementation-ich-e6r3-guideline-notice.html
MHRA Inspectorate. Clinical Trials Regulations: Six-Month Countdown Begins. October 28, 2025.
https://mhrainspectorate.blog.gov.uk/2025/10/28/clinical-trials-regulations-six-month-countdown-begins/
IntuitionLabs. ICH E6(R3) Explained: Key Changes to GCP Guidelines. November 13, 2025.
https://intuitionlabs.ai/articles/ich-e6-r3-gcp-guidelines-2026
Clinical Trial Risk. AI in Clinical Trials: The Edge of Tech.
https://clinicaltrialrisk.org/clinical-trial-design/ai-in-clinical-trials-the-edge-of-tech/
Crescendo AI. The Latest AI News and Breakthroughs in Healthcare and Medical. 2025.
https://www.crescendo.ai/news/ai-in-healthcare-news
ACRPnet. Clinical Research Trends to Expect in 2025: More Complex, Less Connected.
https://acrpnet.org/2025/03/05/clinical-research-trends-to-expect-in-2025-more-complex-less-connected
CDISC. TMF Reference Model General Meeting – Q4 2025.
https://www.cdisc.org/events/webinar/tmf-reference-model-general-meeting-q4-2025
International Council for Harmonisation (ICH). ICH E6(R3) Step 4 Final Guideline.
https://database.ich.org/sites/default/files/ICH_E6%28R3%29_Step4_FinalGuideline_2025_0106.pdf
Arithmos supports sponsors and CROs with independent analytics and clinical services that provide objective insight into TMF quality, oversight, and inspection readiness.
About the Author
Service, Head of Clinical
Rob has spent his whole career in drug development and life sciences with his most recent expertise in Clinical Operations including clinical trial management, essential records, regulations and technology.
Throughout his career, he has led a number of projects for Sponsors, CROs and other Clinical Service Providers. He has experience in Essential Document management, clinical trial processes and modern technologies. Rob has held previous leadership roles managing a global team of TMF subject matter experts supporting clients in everything from simple technical document improvements to complete trial management.
He currently leads our Clinical Services group at Arithmos, where he works across the business units to support our clients with tailored solutions.
About Arithmos
With deep expertise in the Life Science Industry, Arithmos supports companies in their digital transformation journey to achieve the best value from technology-enabled solutions and excellence in business operations.
Arithmos team share extensive knowledge of the full GxP regulated environment for both deliveries of services and technologies, and our domains range from Clinical Development, Quality & Compliance, Pharmacovigilance & Safety and, Regulatory Affairs.
