Ongoing communications generally relate to health product risks associated with known side effects, medication errors, and, in some cases, uncertainty in the evidence. These risks are generally communicated to patients in inserts included with a new medication and in online documents. The information comes from pre-marketing studies, such as side effects detected in randomized controlled trials (RCTs), or as a precaution associated with uncertainties in the evidence (e.g., no pregnant women included in RCTs). Over time, post-marketing monitoring may lead to updates or changes to ongoing communication tools (e.g., the addition of a FDA black box warning, as described below, as a result of a serious ADR detected through pharmacovigilance). Table 3.1 summarizes select examples of these tools.
Table 3.1
Select Ongoing Communication Tools for Health Product Risks Drug Approval Documents
Product Monograph – Health Canada
Description Report-style document with three parts: (i) health professional information, (ii) scientific information, and (iii) medication information.
May include graphs and tables to present risk information and illustrations in selected cases (e.g., images to illustrate where to inject a drug). Quantitative risk information presented in natural frequencies and percentages (in parts 1 and 2). Qualitative risk information provided in part 3.
Varies in length significantly but is generally about 50 pages.
Purpose To inform on the "properties, claims, indications, and conditions of use for the drug, [and] any other information that may be required for optimal, safe, and effective use of the drug."
Target Patients, healthcare professionals
Dissemination Posted on the Health Canada Drug Product Database website (drugs from after January 2004).
It is recommended that the health professional information is included with promotion of the drug, and in any reference manuals distributed.
Examples of
Evaluation None identified.
Summary Basis of Decision (SBD) – Health Canada
Description Report-style document that includes five sections: (i) product and submission information, (ii) notice of decision, (iii) scientific and regulatory basis for decision (largest section), (iv) benefit/risk assessment, and (v) recommendation, submission milestones.
May include graphs and tables to present risk information and illustrations in selected cases (e.g., images to illustrate where to inject a drug). Quantitative risk information presented as frequencies.
Varies in length but is generally about 15–30 pages.
Purpose Scientific and regulatory basis for decision section includes information on the clinical and non-clinical basis for the approval or rejection of a drug. Target Healthcare professionals, general public
Dissemination Posted on the Health Canada website. Examples of
Evaluation
Analysis of SBDs found that “significant omissions in the level of clinical trial information in SBDs provide little to aid clinicians in their decision-making” (Habibi & Lexchin, 2014).
Health Canada evaluation found a little over half of respondents (online workbook) found SBDs “useful in helping them make informed treatment choices (for themselves or their patients)” (Health Canada, 2010).
Summary of Product Characteristics – EMA (European Union)
Description Report-style document.
May include tables and illustrations in selected cases (e.g., images to illustrate where to inject a drug).
For side effects qualitative risk information often given using terms such as rare, very rare, common, etc. (ranges given for qualitative terms). Quantitative information also sometimes given.
Varies in length, but is generally very long (around 100 pages).
Purpose Summarizes all of the information needed to approve a drug (e.g., information for doctors, information for patients).
The basis for all information given to healthcare professionals and for the package leaflet.
Target Healthcare professionals, general public Dissemination Documents posted on the EMA website. Examples of
Evaluation Small study concluded that doctors found it challenging to identify the important points within a summary. Comments included that summaries are muddled and contain considerable repetition (Raynor, 2011; Edwards & Chakraborty, 2012).
European Public Assessment Reports (EPAR) Summary for the Public – EMA (European Union)
Description Text-based document written in a question-and-answer format. Qualitative risk information given for most common side effects. Text provided gives general ranges for qualitative terms (e.g., < 1000). Generally around 2 to 3 pages.
Purpose To inform the general public what the drug is, how it works, why it was approved (i.e., benefits observed in clinical trials), and any associated risks Target General public
Dissemination Published on the EMA website. Examples of
Evaluation EPARs have been criticized for having irregular and unreliable styles of reporting (Barbui et al., 2011).
Consumer/Patient Leaflets Package Insert – Health Canada
Description Leaflet that presents information on a medicine (e.g., dosage, benefits, side effects).
Generally the same as part (i) (health professional information) of the product monograph, but may also include part (iii) (medication information). May include graphs and tables to present risk information and illustrations in selected cases (e.g., images to illustrate where to inject a drug).
Quantitative risk information presented in natural frequencies and percentages. Qualitative risk information also may be included.
Purpose To describe the properties and conditions for use of the drug, including any information that may be required for safe and effective use of the drug, and potential side effects.
Target Healthcare professionals, patients
Dissemination Included in the package of name-brand prescription drugs.
Not required, but if not included the label must state: “Product monograph, package insert or prescribing information available on request.”
Examples of
Evaluation None identified.
Prescribing Information (patient package insert) – FDA (United States)
Description Leaflet that includes information on effectiveness, contraindications, and information of the risks (including side effects) and benefits.
Only needs to be approved for oral contraceptives and estrogen. MHAs often submit patient package inserts to FDA for approval voluntarily.
Quantitative risk information presented in a variety of formats. Qualitative descriptions of risk also used.
May include graphs and tables to present risk information and illustrations in selected cases (e.g., to illustrate the order in which to take birth control pills). Purpose To enable the safe and effective use of a drug by fully informing patients of the
benefits and risks associated with the use of drug.
Target Patients
Dissemination Only required for oral contraceptives and estrogen (considered voluntary for all other drugs).
Included in the package of a drug. Examples of
Evaluation None identified.
Medication Guide – FDA (United States)
Description Paper document that includes information on the side effects and/or drug interactions associated with a medicine.
Considered part of the labelling process.
Qualitative risk information provided (e.g., using terms such as common, rare). Tables and illustrations included in selected cases (e.g., images to illustrate where to apply a gel).
Varies in length but is generally under 10 pages.
Purpose To inform about issues that are specific to that particular drug (or drug class) to help prevent adverse events.
Target Patients
Dissemination Provided with certain prescription medicines (required). Examples of
Evaluation
None identified.
Consumer Medication Information – FDA (United States)
Description Does not need to be approved and can take any form. Examples examined include only text.
Risks listed provide no qualitative or quantitative information (e.g., “these side effects may occur”).
Purpose To provide information for the safe and effective use of a prescription drug or specific over-the-counter medicine.
Target Patients
Dissemination Provided voluntarily by pharmacies with prescription drugs.
Usually included inside or stapled to the outside of the bag containing the medication.
Written by the pharmacy or an outside company. Examples of
Evaluation Evaluation (by experts) of CMIs for two drugs found that these documents had “very low levels of quality” in terms of meeting communication standards/criteria in 14% (drug 1) and 16% (drug 2) of cases
(Kimberlin & Winterstein, 2008).
Product Information – TGA (Australia)
Description Report-style document that contains information on a prescription medication, including pharmacology, indications, precautions, clinical trials,
contraindications, adverse effects, dosage, and storage.
Quantitative risk information presented in natural frequencies and percentages. May include graphs and tables to present risk information.
Generally 10 to 30 pages.
Purpose To “[provide] a summary of the scientific information for the safe and effective use of a prescription medicine.”
Target Healthcare professionals Dissemination Published on the TGA website.
Published in the MIMS Annual and the Prescription Products Guide. Included in full or abridged form in journal advertisements. Examples of
Evaluation None identified.
Consumer Medicines Information – TGA (Australia)
Description Brochure-style document that contains information on a prescription medication, including dosage, precautions, interactions, how to use the medicine, side effects, and how to store the medicine.
Risks listed but no qualitative or quantitative information given (e.g., tell your doctor if you experience these side effects and they worry you). Generally 5 to 10 pages.
Purpose To “[provide] information on the safe and effective use of a prescription medicine.”
Target Patients
Dissemination Required to be “made available to consumers either in the pack or in another manner that will enable the information to be given to the person to whom the medicines are administered or otherwise dispensed.”
Published on the TGA website. Examples of
Evaluation
None identified.
Patient Information Leaflet – EMA (European Union)
Description Leaflet that presents written information on the drug (e.g., dosage, benefits, side effects).
May contain illustrations (e.g., images to illustrate where to inject a drug). Qualitative risk information provided (e.g., using terms such as common, rare). Purpose To describe the properties and conditions for use of the drug, including any
information that may be required for safe and effective use of the drug, and potential side effects.
Target Patients
Dissemination Package leaflet must be included with all medicines. Posted on the EMA website.
Examples of Evaluation
Although no specific evaluation was identified in the EU, patient information leaflets must be tested to ensure they are effective at conveying information (generally use the Australian method) (Edwards & Chakraborty, 2012).
Warnings
Boxed Warnings (“black box warnings”) – FDA (United States)
Description A black box at the top of documents that provides a summary of serious risk. The box includes the word WARNING (in upper case).
Appears on the risk communication documents for a given drug (e.g., package inserts).
Purpose To inform about “certain contraindications or serious warnings [of a drug], particularly those that may lead to death or serious injury.”
Target Healthcare professionals, patients
Dissemination Warning appears in a box at the top of medication insert, entry in the Physicians’ Desk Reference, FDA website, website of drug marketing companies, and other information on the drug.
Examples of
Evaluation Study in Boston found that 0.7% of 324,548 prescriptions issued in 51 outpatient practices violated the boxed warning (highest violations for patients over 75) (Lasser et al., 2006).
Review of evaluations on regulator-issued warnings (black box, dear doctor, and public advisories) found that the intended effects were reported in 29 of 52 cases (56%). Mixed impacts were found in 13 of 52 cases (21%). When unintended effects were assessed, they were almost always present (demonstrating the need to consider unintended effects) (Piening et al., 2012).
Black Triangle Scheme – EMA (European Union)
Description A small black triangle that appears at the top of communication documents for a given drug along with the words: “this medicinal product is subject to additional monitoring.”*
Appears on the risk communication documents for a given drug (e.g., package leaflet).
Purpose To encourage the reporting of adverse reactions by indicating that a product is being monitored more intensively than other health products (e.g., because of uncertainty associated with a new-to-market drug).
Target Healthcare professionals, general public
Dissemination Appears on the package leaflet and summary of product characteristics. Appears on the EMA website for the drug.
Examples of
Evaluation None identified.
* Text as it appears in the United Kingdom. Sources: (Wooler, 1995; EMA, 2006, 2009, 2014b, 2014c; FDA, 2006, 2007a, 2013; Health Canada, 2010, 2014d, 2014e; TGA, 2014d, 2014f)
The most common document for presenting risk information is the package insert, some form of which exists in all jurisdictions. In Canada, all prescription drugs must either include a package insert or a statement on the packaging that the product information is available on request (Health Canada, 2014d). The EMA requires inserts for all medicines; the FDA requires them for certain medicines; and the TGA requires that they be “made available to consumers either in the pack or in another manner.” In the European Union, inserts (i.e., patient information leaflets) must be tested by MAHs (i.e., pre-testing evaluation) to ensure that they are effective at conveying information. EU regulations state that “the package leaflet shall reflect the results of consultations with target patient groups to ensure that it is legible, clear and easy to use” (European Parliament, 2001). Generally, an MAH undertakes face-to-face interviews with members of the general public to meet these requirements. Package inserts generally give risk information in qualitative terms, although in some cases quantitative ranges are given (e.g., a side effect is expected in 10 out of every 1,000 people who take a drug). Canada and the United States have no testing requirements (Edwards & Chakraborty, 2012). While inserts generally present information in a similar way in all jurisdictions, there are a few notable exceptions. In EU member states, a small black triangle appears at the top of the package leaflet and summary of product characteristics to indicate that a product is being monitored more intensively than other health products because of the presence of uncertainty in the evidence (usually related to long-term effects of a drug that is new to the market) (EMA, 2014c). While the purpose of the triangle is to encourage the reporting of adverse reactions, it also serves as a simple visual cue to quickly convey a particular type of risk information (i.e., uncertainty). In “exceptional cases,” the EMA also has the option to propose the inclusion of a boxed warning (in bold) in the summary of product characteristics (in the section on special warnings and precautions for use) (European Commission, 2009). Black box warnings in the United States are also a simple visual cue to indicate a particular type of risk, in this case a serious warning. These warnings appear at the top of any document used to provide information on the drug (e.g., insert, promotional material) (FDA, 2013).
All jurisdictions post online a wide range of ongoing communication documents, which vary in length and in intended targets. Those intended for the general public (e.g., part 3 of Health Canada’s product monograph and the EMA’s EPAR for the public) are generally much shorter than those for other audiences and often do not include quantitative information. More detailed documents aimed at healthcare professionals, which are longer and contain more medical terminology, are also available online.
In general, the Panel found few publicly available evaluations of ongoing communication tools (see Table 3.1 for examples). For all tools except black box warnings, evaluations primarily related to measuring either the quality of a tool’s content or whether users could understand content. These evaluations relied on either individual interviews or expert analysis and were mainly conducted at the end-stage, with the exception of evaluation of the package inserts in the European Union, which is conducted at the pre-testing stage by law. In the case of black box warnings, Piening et al. (2012) identified 15 evaluation studies, all of which were outcome measures of use and impact. Common indicators for measuring effectiveness were prescription rates, new users, or overall drug use volume.