EU joint clinical assessment, one PICO per row: its evidence, its gap, its section and its next step on the 100-day clock
Every PICO answered, cited and on the clock: a full draft dossier by day 39 of 100.
See one case, screen by screen ↓Under the EU HTA Regulation (EU) 2021/2282, new cancer medicines and advanced therapies whose marketing authorisation application was filed with EMA from 12 January 2025 get one joint clinical assessment at EU level, which Member States must give due consideration in their national HTA; orphan medicines join in January 2028 and all new medicines in 2030. The Member States state their needs as PICO questions, the assessors consolidate them into one scope, and the developer submits a dossier that answers every PICO.
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The Member States say what they need as PICO questions, and the assessors consolidate them into one assessment scope. From that scope the dossier is due on the HTA IT platform in about 100 days, and it has to answer every PICO — with head-to-head data, an indirect comparison or a justified gap. Eleven PICOs with eight outcomes each is 88 evidence cells, each to be found in a clinical study report, a statistical output or a published trial, or declared a gap. Teams track the work in spreadsheets.
The risk is the PICO nobody looked at closely enough. A comparator asked for by one or two countries — Germany's physician's choice of three options — is the easiest to overlook. A PICO with no head-to-head data needs an indirect-comparison plan agreed with biostatistics before any result exists; if that decision slips, the results and the sections that report them slip with it, and the gap is found when the comparison deadline is already close.
Estimated split, in days, from the assessment scope to a full draft dossier — about 70 by hand (our estimate) against the 39-day target with the solution.
Six specialist agents read the scope, fill each PICO's evidence, flag rows with no head-to-head data, plan comparisons, draft and check; the statistician and dossier lead approve and sign.
Corventa (corventamab vedotin), an antibody–drug conjugate for previously treated non-squamous NSCLC, is in joint clinical assessment JCA-26-014 — assessor the Netherlands, co-assessor Spain. The scope arrived on Aug 31; today is day 37 of 100. Here is what happens next, screen by screen, in the working solution.
The PICO grid shows one row per PICO question: population, comparator, eight outcome squares coloured by evidence, the Member States that asked, the evidence verdict with its key number and the dossier section that answers it. The countdown reads 63 days to submit on the HTA IT platform — due Wed Dec 9, 45 days before the CHMP opinion. Three rows have head-to-head data, three weak evidence only, and two are red.
“Next: PICO decisions signed off · day 44 · Oct 14 · in 7 days”
The scope parser reads scope v1.0 — 14 pages, 11 PICO questions from 27 Member States — in 19 seconds. The evidence mapper reads the CRV-301 report, 1,246 outputs and the analysis plan into 88 outcome cells. The literature review matcher finds 7 included trials, with docetaxel connecting PICOs 2, 3, 4 and 8. The rows come back one by one, and the ones without head-to-head data turn red.
Comparison feasibility analyst: “2 PICOs without head-to-head data — both comparators Germany asked for.”
PICO 2 asks about adenocarcinoma histology against docetaxel plus an angiokinase inhibitor, for Germany, Austria, Czechia, Slovakia, Hungary, Romania and Bulgaria. No trial compared them: the row reads “No trial · Bucher plan waits for you”. Its detail shows the planned values — OS HR 0.92, PFS HR 0.82 — a quality-of-life gap because the scales differ, section 6.2 as the answer and the next step: approve the comparison plan, day 44. PICO 7, physician's choice of three for Germany and Austria, is red too: the trial offered docetaxel only.
The matrix is 11 PICOs by 8 outcomes, each cell marked direct, indirect, planned, uncertain or gap — 6 need a decision, 16 are gaps, 13 are post hoc. Opening PICO 1 overall survival shows HR 0.78 (0.65–0.94), median 13.1 vs 10.2 months, moderate certainty, with the CRV-301 clinical study report open at Table 14.2.1.1, page 612, and the numbers highlighted.
The evidence mapper takes numbers only from a cited table or output, and never computes a comparison itself.
Seven gaps, five open. For PICO 2 the analyst builds the evidence network — the CRV-301 adenocarcinoma subgroup (n = 548) and a published 2014 trial (n = 658) share docetaxel at the same dose, 75 mg/m² every 3 weeks. Histology, line of therapy, performance status and proportional hazards (Schoenfeld p = 0.21) check out; follow-up differs, a median of 18.2 vs 31.7 months. Every check cites its source passage, and one fails.
“Prior immunotherapy: 100% in CRV-301 vs 0% in the comparator trial — a likely effect modifier.”
Sam Patel recommends approving the plan with a sensitivity analysis restricted to patients with at least 6 months of prior anti-PD-(L)1 therapy. Lena has three choices: approve the plan, approve with the sensitivity analysis, or declare an evidence gap and explain why in the dossier. She picks the sensitivity analysis and writes the note for the record: “Prior immunotherapy differs between trials; sensitivity analysis to show robustness.”
“Signing as Dr. Lena Ortiz · dossier lead · the run starts on approval”
The plan is locked as comparison plan v1.0 with Sam's recommendation attached. The statistics engine runs the Bucher comparison on OS, PFS, response and four safety outcomes, then the sensitivity analysis — HR 0.95 (0.71–1.27) — and a second program reproduces every estimate to 3 decimals. Six PICO 2 cells are updated: on the grid the row turns blue, “Indirect comparison · Bucher via docetaxel · OS HR 0.92”, with its next step “Draft section 6.2”.
“All overall survival intervals cross 1: no statistically significant difference. Certainty low — no patient in the comparator trial had received immunotherapy.”
The writer drafts section 6.2 from the matrix and the comparison results — evidence base, overall survival, progression-free survival and response, safety, quality of life and certainty — 1,180 words, 14 citations, sent to Priya Raman for review. Each citation opens its source: the assessment scope's PICO 2 on page 4, the published trial, the comparison run, the CRV-301 baseline tables.
The dossier writer never claims superiority where the interval crosses 1, and uses no promotional language.
The consistency checker compares 1,846 numbers with their tables and outputs — all match — and the indication wording with SmPC draft v3.2: section 3 says “advanced” where the SmPC says “locally advanced or metastatic”. One click takes the SmPC wording. Post hoc values are labelled and every PICO has a results section, so Lena signs v0.6 with the meaning “Approved for internal review”. Dr. Maya Chen reviews the results next; Omar Haddad signs the final dossier on day 96.
“Signed · meaning: approved for internal review · Dr. Lena Ortiz · v0.6 · Oct 7, 2026”
The same assessment, seen by the five people who carry it — what their 100 days looked like, and what they look like now.
Six specialist agents read the scope, fill each PICO's evidence, flag rows with no head-to-head data, plan comparisons, draft and check; the statistician and dossier lead approve and sign.
Reads the assessment scope from the assessors and turns it into structured PICO questions — population, comparators, outcomes — with the Member States behind each one and the page and sentence each element came from. A revised scope is compared with the previous version.
Reads clinical study reports, protocols, analysis plans and statistical outputs and puts the best evidence into every PICO × outcome cell — head-to-head first, then subgroups, then single-arm data — with its interval, population, data cut-off and table.
Links the studies included in the systematic literature review to the comparators in the scope, builds the evidence network and finds which trials share a common comparator.
For every gap, proposes the indirect comparison method and checks feasibility — common comparator, effect modifiers, proportional hazards, sample size — following the HTA Coordination Group guidance. Prefers anchored methods; where no anchor exists it proposes a matching-adjusted comparison and reports the effective sample size.
Drafts each section in the order of the JCA dossier template, in plain, neutral language, reporting every PICO and outcome the scope asks for — including where there is no evidence — and citing the source of every number.
Compares every number in the dossier with its cited output to the last decimal, the indication and population wording with the latest SmPC draft, and confirms every PICO has a results section and every post hoc analysis is labelled.
Approve plans, sign the dossier. The agents propose; a named person decides.
Ask about any PICO, comparison, number or deadline. Every answer points to the scope, the study report, the output or the review it came from.
Where does the PICO 2 comparison stand?
Feasible but waiting for you. Both trials share docetaxel, so a Bucher comparison works: feasibility estimate OS HR 0.92 (0.70–1.20). The concern is prior immunotherapy — 100% in CRV-301, 0% in the comparator trial. Sam Patel recommends approving with a sensitivity analysis. Plans are due Oct 14.
Why is there no evidence against best supportive care?
PICO 5 asks about patients with ECOG 2 or not suitable for docetaxel. CRV-301 excluded ECOG 2 by protocol, so there is no comparative evidence. The only data are the 14-patient ECOG 2 cohort of phase 2 CRV-201: response 21.4%, single arm. The agents drafted a justification to declare this as an evidence gap — it waits for you.
How do we handle the EGFR / ALK PICO?
PICO 6 compares with a platinum doublet, which no Corventa trial used. The only option is an unanchored matching-adjusted comparison from the 61-patient CRV-201 cohort. After weighting, the effective sample is 23.4 of 61 (38%); OS HR 0.71 (0.42–1.20). It will be rated very low certainty.
How many days do we have left?
63 days. Day 0 was Aug 31, when the scope arrived; today is day 37. The dossier is due on the HTA IT platform on Wed Dec 9 (day 100). Comparison plans are signed off on day 44 (Oct 14), comparison results are final on day 60, the full draft v1.0 is due on day 75 and final sign-off is day 96 (Dec 5).
13 screens from the working solution, on its sample data. Pick one to see it large.
The milestones, who signs what and the evidence rules every dossier is held to are settings.
| Setting | Default | Choose from |
|---|---|---|
| Dossier window | 100 days | 100 days · 90 days |
| Comparison plans signed off | Day 44 | Day 40 · Day 44 · Day 50 |
| Full draft dossier | Day 75 | Day 70 · Day 75 · Day 80 |
| Final sign-off | Day 96 | Day 95 · Day 96 · Day 98 |
| Indirect comparison plans | Sam Patel → Dr. Lena Ortiz | Sam Patel → Dr. Lena Ortiz · Sam Patel only |
| Final dossier | Omar Haddad | Omar Haddad · Dr. Lena Ortiz |
| Warn when the matched sample shrinks | Below 40% of patients | Below 30% · 40% · 50% of patients |
| Numbers without a source block signing | On | On · Off |
Every figure is labelled: a target the solution is built to, an estimate, a typical published result, or a proven one.
“demo” = seen in the working solution, on its sample assessment data · “target” = the design goal, measured in the live solution · “estimated” = our estimate (about 70 days by hand) · “typical” = published figures (first-year reports, 2026, on 8–13 PICOs per scope and the 90–100-day window). Context: Regulation (EU) 2021/2282 on health technology assessment and Implementing Regulation (EU) 2024/1381. People, products, trials and assessments named on this page are fictional — characters and sample data in the working solution.
Under the EU HTA Regulation (EU) 2021/2282, new cancer medicines and advanced therapies whose marketing authorisation application was filed with EMA from 12 January 2025 get one joint clinical assessment at EU level, which Member States must give due consideration in their national HTA; orphan medicines join in January 2028 and all new medicines in 2030. The Member States state their needs as PICO questions, the assessors consolidate them into one scope, and the developer submits a dossier that answers every PICO.
The scope parser turns it into a PICO grid — one row per PICO with the Member States behind it and the source sentence of every element. The evidence mapper fills the eight outcomes of every row from study reports, outputs and published trials, and rows with no head-to-head data turn red. Each row is owned by one dossier section and carries its next dated step on the 100-day clock.
The comparison feasibility analyst proposes a method for each gap — an anchored Bucher comparison or network meta-analysis where a common comparator exists, a matching-adjusted comparison with its effective sample size where none does, or a justified gap — and checks effect modifiers, proportional hazards and sample size with citations. The biostatistician recommends, the dossier lead decides, and only approved plans run.
The dossier writer drafts each section in the order of the JCA dossier template, in neutral language, with every number cited and uncertain results described as uncertain. The consistency checker then compares every number with its source and the wording with the SmPC draft. People review each section, and the dossier lead signs every version.
Yes. The agents never merge or drop a PICO, never compute a comparison on their own and never edit silently. A biostatistician recommends each comparison, the dossier lead approves it and signs each version with its meaning, and the head of market access signs the final dossier for upload.
A revised scope is compared with the previous version. A changed PICO reopens the dossier sections it touches, moves them back to draft and tells their owners.
Yes. The dossier window (100 or 90 days), the days for comparison plans, the full draft and final sign-off, who recommends and approves comparison plans, the clinical, SmPC and final signers, the matched-sample warning threshold and the reminders are all settings.
The Agentic Solution Engine builds and deploys it from your requirements and documents — your dossier template, study reports, statistical outputs and a past assessment scope — and it goes live once every quality gate has passed. We will walk you through it on one of your own scopes first.
A checked first-draft protocol in days, in your approved language.
1-min demoeTMF Quality CheckAn inspection-ready trial master file every day, each site scored on what is due today.
1-min demoClinical Study Report AuthoringResults drafted within days of database lock, linked to tables.
1-min demoWe'll run EU Joint Clinical Assessment on one of your own assessment scopes and its study reports.