How do you generate real-world evidence that convinces HTA bodies, regulators and payers beyond the pivotal trial?
We design observational, registry and secondary-data studies whose endpoints and comparator groups are aligned, from the study design stage onward, with the questions raised by the G-BA, EMA and payers. Real-world evidence is not a replacement for the randomized trial; it answers the questions the trial leaves open: effectiveness in routine care, long-term safety and subgroups that were too small in the RCT. The most common mistake is not poor data quality, but adjusting the research question to the assessment question only after the data have been collected; at that point the appropriate control group is irretrievably missing.
- Pharma
- Biotech
- MedTech
- IVD
Overview
When do HTA bodies, regulators and payers require real-world evidence?
RWE design for pharma registries, MedTech PMCF and IVD PMPF · ICH E6(R2) GCP, MDR (EU) 2017/745, IVDR (EU) 2017/746
Last updated: 2026-06-13
The randomized controlled trial remains the gold standard for demonstrating efficacy, but it does not answer every question that arises after approval. Real-world evidence closes these gaps, provided that the question and the design match the assessment logic of the recipient. The typical triggers:
- Benefit assessment beyond approval: HTA bodies ask about the added benefit in routine care and about long-term data. The HTA Regulation (EU) 2021/2282 establishes the joint clinical assessment at EU level; national assessments continue to require, in addition, evidence on patient-relevant endpoints under routine conditions.
- Post-market clinical follow-up for medical devices: The MDR (EU) 2017/745 requires, under Annex XIV Part B, an ongoing PMCF plan that systematically collects clinical data in the market and feeds them back into the clinical evaluation.
- Post-market performance follow-up for IVDs: The IVDR (EU) 2017/746 requires, under Annex XIII Part B, a PMPF as part of the performance evaluation: continuous confirmation of clinical performance throughout the entire lifecycle.
- Long-term safety and signal generation: Observational studies and registries deliver the safety data on rare events and subgroups that an RCT with limited sample size and duration cannot cover; planning follows the pharmacovigilance logic of ICH E2E.
- Data protection as a design prerequisite: Every collection of health data is subject to the GDPR (EU) 2016/679; the legal basis, consent and an anonymization or pseudonymization concept must be in place before the study starts, not afterward.
Services
How we support you
Study Design & Protocol
Definition of the directed research question, selection of the design (prospective, retrospective, hybrid), specification of patient-relevant endpoints and comparator groups. The deliverable is an aligned study protocol with a statistical analysis plan.
Pharma Registry Studies
Design and conduct support for non-interventional studies and disease or product registries in line with ICH E6(R2). The deliverable is the registry protocol with data model, consent documents and analysis strategy.
MedTech PMCF & IVD PMPF
Development of PMCF plans under MDR Annex XIV Part B and PMPF plans under IVDR Annex XIII Part B, linked to the clinical evaluation and performance evaluation respectively. The deliverable is the documented plan including the PMCF/PMPF evaluation report.
Learn more →Secondary and Claims Data Analysis
Use of existing routine and claims data as a source of evidence, including assessment of data quality, representativeness and confounding. The deliverable is a feasibility assessment with a description of data sources and methodology.
HTA-Compatible Data Strategy
Alignment of endpoints and comparators with the requirements of HTA bodies and payers under the HTA Regulation (EU) 2021/2282. The deliverable is an evidence strategy that interlocks RWE studies with HTA and reimbursement logic.
How we work together
What it comes down to
Are the data from the pivotal trial still enough? For the primary demonstration of efficacy, the randomized controlled trial remains the gold standard. But HTA bodies, regulators and payers ask about what it leaves open: effect in routine care, long-term safety and subgroups that were too small in the RCT. Real-world evidence answers precisely these questions, but only if the research question is in place before the data are collected. The decisive hurdle is rarely data quality, but sequence: those who look for the appropriate comparator group only after collection no longer find it, and the conclusion loses its probative value in front of the assessment recipient.
That is why we order the design around the recipient. For medical devices and IVDs, the direction is set by the regulation: PMCF under MDR (EU) 2017/745 Annex XIV Part B and PMPF under IVDR (EU) 2017/746 Annex XIII Part B are ongoing systems that feed data back into the clinical evaluation and the performance evaluation respectively, not a one-off report. For medicinal products, the RWE question is directed at benefit assessment and reimbursement, structured by the HTA Regulation (EU) 2021/2282. In both cases the same rule applies: the data protection concept under GDPR (EU) 2016/679 and the statistical methodology against confounding belong at the start, not at the end. This is how evidence is created that withstands the assessment, instead of expensive data without probative value.
Our approach
Our approach
Step
Result
Evidence Gap & Research Question
A defined, directed research question and the specific recipient (HTA, regulator, payer) to whose assessment logic the design is aligned.
Design & Data Strategy
A defined study design, data source and comparator group; decision between primary collection, registry and secondary data.
Protocol & Data Protection
A study protocol with statistical analysis plan and a GDPR-compliant data protection concept including legal basis and consent.
Conduct & Data Collection
An ongoing study with quality-assured data management in line with the principles of ICH E6(R2).
Analysis & Report
Statistical analysis and a study report with statements on patient-relevant endpoints, aligned with the assessment recipient.
Integration into PMCF/PMPF & Dossier
Evidence fed into the PMCF/PMPF report, HTA dossier or value dossier as a robust building block of the overall argument.
Common pitfalls
Where projects commonly fail
The research question is adjusted to the assessment question only after the data have been collected.
Without a comparator group defined in advance, the relevant comparison can no longer be established later; this is the most expensive correction loop in the entire RWE project, because it usually forces a new round of data collection.
PMCF under MDR Annex XIV Part B is understood as a one-off study rather than an ongoing plan.
The notified body expects a continuous system that feeds data back into the clinical evaluation; a completed single report does not satisfy this obligation.
Secondary and claims data are used as proof of efficacy without a confounding analysis.
Routine data are subject to selection and indication bias; without adequate methodology (such as adjustment or suitable comparator groups), the conclusion will not withstand HTA scrutiny.
The data protection concept under GDPR (EU) 2016/679 is clarified too late.
A missing legal basis, incomplete consent or an unverified anonymization concept blocks the study start or renders collected data unusable.
RWE is positioned as a replacement for the randomized trial rather than as a complement.
Regulators and HTA bodies accept RWE for defined questions (routine care, long term, subgroups), not as a blanket substitute for the RCT; an overstated positioning weakens the entire argument.
FAQ
Frequently asked questions
Sources
- Regulation (EU) 2017/745 (MDR), primary text, Annex XIV Part B (PMCF)
- Regulation (EU) 2017/746 (IVDR), primary text, Annex XIII Part B (PMPF)
- Regulation (EU) 2021/2282 on health technology assessment (HTA Regulation), primary text
- ICH E6(R2), Good Clinical Practice
- ICH E2E, Pharmacovigilance Planning
- Regulation (EU) 2016/679 (GDPR), primary text
- https://theentourage.de/expertise/real-world-evidence/ (existing page content, revised)
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Case Studies
What this looks like in practice
Related insights
All insights →Regulations & standards considered
- EU 2017/745 (MDR)
- MDR Annex XIV Part B (PMCF)
- EU 2017/746 (IVDR)
- IVDR Annex XIII Part B (PMPF)
- Regulation (EU) 2021/2282 (HTA Regulation)
- ICH E6(R2) (Good Clinical Practice)
- ICH E2E (Pharmacovigilance Planning)
- Regulation (EU) 2016/679 (GDPR)
Related topics
HEOR & Modeling →
Health-economic modeling that translates RWE data into proof of benefit
HTA Dossier →
Preparation of the evidence for the HTA assessment under EU 2021/2282
Post-Market Surveillance →
PMCF under MDR Annex XIV and PMPF under IVDR Annex XIII as a system
Market Access Strategy →
Interlocking the evidence strategy with payer and reimbursement logic
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