Patient Information Leaflet

Patient Information Leaflet in Medicines Regulation and Health Technology Assessment

The patient information leaflet, called the package leaflet in EU and UK medicines law, is the sheet in the box that tells a patient in lay language what a medicine is for, how to take it and which side effects to watch for. Its content is set by law, approved with the product and bound to the summary of product characteristics (SmPC), the regulator-approved technical summary of the medicine. A 2005 report for the UK regulator found that for many people it is the only information they have about their medicines. For health technology assessment it matters because it restates the licensed indication that bounds an appraisal, and because its effects on medicine-taking are less certain than its legal status suggests.

What EU and UK law requires in a package leaflet

Directive 2001/83/EC, in its amended text as it stood on 31 December 2020, defines the package leaflet as a leaflet containing information for the user which accompanies the medicinal product, and Article 58 makes one obligatory in every pack unless all the required information appears on the packaging. Article 59(1) requires it to be drawn up in accordance with the SmPC and fixes its order, from therapeutic indications and contra-indications through dosage, missed doses and adverse reactions to the date of last revision.

Amendments made by Directive 2010/84/EU added a standardised text asking patients to report suspected adverse reactions to a health professional or directly to the national spontaneous reporting system, which ties the leaflet to adverse event reporting. Article 63(2) requires the leaflet to be clear and understandable, enabling users to act appropriately. Under Article 61 the draft leaflet goes to the regulator with the marketing authorisation application, with the results of assessments carried out with target patient groups, and the authority must refuse the authorisation if the leaflet is not in accordance with the SmPC.

In the UK the same duties sit in the Human Medicines Regulations 2012. Regulation 260 requires a leaflet drawn up in accordance with the SmPC that is legible, clear and easy to use, with target patient groups consulted to achieve this, and regulation 267 requires the draft and the test results to be submitted with the application. The MHRA's best practice guidance of 2012 records that leaflets have been a legal requirement in the UK for all medicines since 1999. Its current guidance, updated in July 2026, still refers applicants to that best practice guidance and to the Commission readability guideline.

How readability is tested before approval

Article 59(3) requires the leaflet to reflect consultations with target patient groups so that it is legible, clear and easy to use. The European Commission's readability guideline (Revision 1, 12 January 2009) explains that this requirement came in with Directive 2004/27/EC, calls it user consultation, and sets a minimum type size of 9 points in Times New Roman with at least 3 mm between lines.

Success is judged question by question. The guideline treats a user test as satisfactory when 90% of participants can find each piece of requested information and 90% of those can show that they understand it, which it expresses as 16 of 20 participants finding the information and answering correctly, and results cannot be aggregated across questions. The MHRA expects two rounds of 10 participants on the final leaflet, with revision and retesting when results fall short.

Medication Guides and patient package inserts in the United States

Under 21 CFR Part 208 the FDA requires a Medication Guide, FDA-approved patient labelling, when it determines that a prescription product poses a serious and significant public health concern, for example because labelling could help prevent serious adverse effects, or because the product is important to health and patient adherence to directions for use is critical to its effectiveness. A Medication Guide must be based on, and must not conflict with, the approved professional labelling, the US counterpart of the SmPC consistency rule. Patient package inserts are narrower, and 21 CFR 310.501 requires each dispenser of an oral contraceptive to give the patient one.

In May 2023 the FDA proposed a one-page Medication Guide with standardised format and content, called Patient Medication Information, for prescription products used on an outpatient basis, and proposed removing the patient package insert requirements. Its preliminary economic analysis counted lower search costs for information and possibly reduced risk as benefits, with primary estimates of USD 1.6 billion in present-value benefits over 10 years at a 3% discount rate against net costs of USD 192.8 million. A July 2026 FDA notice still described it as a proposed rule and added related comments to its rulemaking docket for continued consideration.

The licensed indication and the scope of an appraisal

The leaflet's indications and dosage restate sections 4.1 and 4.2 of the SmPC. The same particulars bound a technology appraisal. The NICE manual (PMG36, section 2.2.3) states that for medicines the relevant use will normally depend on the expected marketing authorisation, and section 2.2.6 says that, unless the Department of Health and Social Care indicates otherwise, NICE will not develop technology appraisal guidance for indications without UK regulatory approval.

A recommendation that a technology can be used is worded as use within its marketing authorisation (PMG36, section 6.4, table 6.3). The population and dosing in the decision problem therefore normally fall within the licensed use that the leaflet describes to patients.

Adherence, side effects and the value of a medicine

Hughes and colleagues reviewed 22 economic evaluations that varied compliance and found that in these models non-compliance always reduced efficacy, although most assumed this without supporting clinical evidence, while its effect on costs varied substantially. They warned that ignoring real-world compliance may lead to sub-optimal treatment choices, so medication adherence is a parameter worth testing in deterministic sensitivity analysis.

Evidence that leaflets change behaviour is weak. The Cochrane review by Nicolson and colleagues included 25 randomised trials with 4,788 participants and found that written information significantly improved knowledge in 6 of 12 trials that compared it with none, but results for attitudes and behaviour were mixed and the evidence was not strong enough to say whether it changes medicine-taking. The NIHR HTA review by Raynor and colleagues found that most people did not value the written information they received, citing complex language and poor visual presentation. It also recorded that some health professionals saw increasing compliance as a prime function, whereas patients saw an informed decision not to take a medicine as an acceptable outcome, so scoring a leaflet only by adherence would count informed refusals as failures.

Wording about side effects may change the side effects reported. In a pilot randomised trial of 102 orthopaedic surgery patients taking ibuprofen, Prediger and colleagues found ibuprofen-specific adverse events in 23.5% of patients given the standard leaflet, 17.1% given a simplified plain-language leaflet and 12.1% given no leaflet. The adjusted relative risks against the standard leaflet were 0.80 and 0.50, with confidence intervals including 1, so the effect is unproven.

Worked example of the cost per QALY of a clearer leaflet

All numbers in this example are illustrative. A health system expects a single cohort of 10,000 people to start a preventive medicine, and 60% take it as directed. A redesigned, user-tested leaflet costs GBP 25,000 to introduce and raises the share taking the medicine as directed to 62%. Each additional adherent person gains 0.05 QALYs, uses GBP 300 more of the medicine and avoids GBP 100 of event costs, a net cost of GBP 200.

The redesign adds 10,000 × 0.02 = 200 adherent patients, who gain 200 × 0.05 = 10 QALYs at an incremental cost of 200 × 200 + 25,000 = GBP 65,000.

$$\text{ICER} = \frac{\Delta C}{\Delta E} = \frac{65000}{10} = 6500$$

where $\Delta C$ is the incremental cost in GBP and $\Delta E$ is the incremental QALYs, so the redesign costs GBP 6,500 per QALY gained. If adherence rose by only 0.5 percentage points, 50 more patients would gain 50 × 0.05 = 2.5 QALYs at a cost of 50 × 200 + 25,000 = GBP 35,000, an ICER of GBP 14,000 per QALY.

As the adherence effect grows, the ICER approaches the medicine's own cost per QALY among adherent patients, GBP 200 per 0.05 QALYs or GBP 4,000 per QALY, and when the effect is small the fixed cost of the leaflet dominates. A clearer leaflet improves value only if the medicine is good value in the people it persuades to adhere, and a redesign that helps people unlikely to benefit decide to stop could improve value while lowering adherence.

Leaflets compared with decision aids and other product information

Several documents describe a medicine. The table compares the main ones.

In the Cochrane review by Stacey and colleagues, patient decision aids at a minimum make the decision explicit, give evidence-based information about options and their benefits and harms, and help clarify personal values. A leaflet describes one medicine and does neither of the other two. The review counts general information as usual care, so in trials of decision aids leaflet-style information sits on the comparator side.

Economically, the leaflet is a mandated disclosure addressing information asymmetry between the maker of a medicine and the person taking it. The applicant bears the duty to draft and test it, and the MHRA presents good information as helping patients take part fully in decisions about their medicines.

Common misreadings of the patient information leaflet

Approval does not mean a leaflet is read and understood. It shows that the content matches the SmPC and that a test panel could use it, not that patients act on it.

A passed user test does not cover every patient. The success criteria published in 2005 refer to literate adults, and the same report noted that people with sight loss, people whose first language is not English and people with poor literacy or numeracy may have problems with the standard leaflet.

The leaflet does not cover every use of the medicine. A patient prescribed a medicine off-label receives a leaflet whose indications, taken from the SmPC, do not mention that use, which NICE would not normally have appraised either.

Sources

• European Commission. Guideline on the readability of the labelling and package leaflet of medicinal products for human use. Revision 1. Brussels: European Commission; 12 January 2009. https://health.ec.europa.eu/system/files/2016-11/2009_01_12_readability_guideline_final_en_0.pdf
• European Parliament and Council of the European Union. Directive 2001/83/EC of 6 November 2001 on the Community code relating to medicinal products for human use. Official Journal of the European Communities. 2001;L311:67-128. Articles 1, 11, 58, 59, 61 and 63, revised text as at 31 December 2020 on legislation.gov.uk. https://www.legislation.gov.uk/eudr/2001/83/contents
• Food and Drug Administration. Medication guides: patient medication information. Proposed rule. Federal Register. 2023;88(104):35694. https://www.federalregister.gov/documents/2023/05/31/2023-11354/medication-guides-patient-medication-information
• Food and Drug Administration. Medication guides for prescription drug products. Information collection notice. Federal Register. 2026;91(125):40000-40002. https://www.federalregister.gov/documents/2026/07/01/2026-13346/agency-information-collection-activities-submission-for-office-of-management-and-budget-review
• Food and Drug Administration. 21 CFR Part 208, Medication guides for prescription drug products, and 21 CFR 310.501, Patient package inserts for oral contraceptives. eCFR, accessed 14 October 2026. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-C/part-208
• Hughes DA, Bagust A, Haycox A, Walley T. The impact of non-compliance on the cost-effectiveness of pharmaceuticals: a review of the literature. Health Economics. 2001;10(7):601-615. https://doi.org/10.1002/hec.609
• Medicines and Healthcare products Regulatory Agency. Always read the leaflet: getting the best information with every medicine. London: TSO; 2005.
• Medicines and Healthcare products Regulatory Agency. Best practice guidance on patient information leaflets. London: MHRA; July 2012. https://assets.publishing.service.gov.uk/media/5a7e30c440f0b62302689bec/Best_practice_guidance_on_patient_information_leaflets.pdf
• Medicines and Healthcare products Regulatory Agency. Medicines: packaging, labelling and patient information leaflets. GOV.UK; updated 1 July 2026. https://www.gov.uk/guidance/medicines-packaging-labelling-and-patient-information-leaflets
• National Institute for Health and Care Excellence. NICE technology appraisal and highly specialised technologies guidance: the manual (PMG36). London: NICE; 2022, last updated 13 October 2026. Sections 2.2.3, 2.2.6 and 6.4 (table 6.3).
• Nicolson D, Knapp P, Raynor DK, Spoor P. Written information about individual medicines for consumers. Cochrane Database of Systematic Reviews. 2009;(2):CD002104. https://doi.org/10.1002/14651858.CD002104.pub3
• Prediger B, Meyer E, Büchter R, Mathes T. Nocebo effects of a simplified package leaflet compared to unstandardised oral information and a standard package leaflet: a pilot randomised controlled trial. Trials. 2019;20:458. https://doi.org/10.1186/s13063-019-3565-3
• Raynor DK, Blenkinsopp A, Knapp P, et al. A systematic review of quantitative and qualitative research on the role and effectiveness of written information available to patients about individual medicines. Health Technology Assessment. 2007;11(5):1-160. https://doi.org/10.3310/hta11050
• Stacey D, Lewis KB, Smith M, et al. Decision aids for people facing health treatment or screening decisions. Cochrane Database of Systematic Reviews. 2024;(1):CD001431. https://doi.org/10.1002/14651858.CD001431.pub6
• The Human Medicines Regulations 2012 (SI 2012/1916). Part 13, regulations 259, 260 and 267. https://www.legislation.gov.uk/uksi/2012/1916/part/13