Dr. R. Vander Stichele Department of Pharmacology Heymans Institute of Pharmacology

Impact of written drug information in patient package inserts. Acceptance and benefit/risk perception. Dr. R. Vander Stichele Department of Pharmacology Heymans Institute of Pharmacology May 27, 2004

Preliminary observations (1) In developped countries 10 packages per citizen per year of prescribed medicines are distributed in pharmacies. Putting a package insert in every package adds a few percentages to the cost of distributing medicines. In Europe, unit-of-use distribution (exclusive use of branded packages of fixed strenght and size) with a patient package insert in every package is the rule since 1992. In other continents this distribution system is not (yet) applied.

Preliminary observations (2) In most countries the Regulatory Health Authorities agree with the principle that patients should be well informed about the risks of medicines. Opinions are split, however, about the usefulness of written drug information in understandable patient package inserts.

Preliminary observations (3) In some countries, Regulatory Health Authorities are convinced that oral drug information from the physician and the pharmacist is sufficient. Other Regulatory Health Authorities see understandable written drug information for patients as a useful instrument, however, to be distributed on a voluntary basis. In Europa it was decided that understandable patient package inserts should be included in all packages.

Problem • There is still doubt whether : • package inserts are read by patients • package inserts have effect • package inserts might have detrimental effects • (e.g. less patient compliance)

Research questions • Do patients accept (undertstandable) package inserts ? • What are the effects of (understandable) package inserts ? • How can we improve patient package inserts (PPIs) ?

Overview of the studies in the thesis • 1. Descriptive studies • 8 studies, specifically focussing on the introduction of patient package inserts in Belgium (1988-2001) • 7 general studies on the role of patient package inserts in the ederly, adolescents, in institutions (hospital, nursing home). • 2. Intervention studies of the effects of package inserts • 3 randomized clinical trials • 1 randomized experimental psychology study .

Time perspective of these studies Belgian Law on PPIs European Directive on PPIs Transition in Belgium to PPIs 1985 1990 1995 2000

Time perspective of these studies Belgian Law on PPIs European Directive on PPIs Descriptive studies Intervention studies Transition in Belgium to PPIs 1985 1990 1995 2000

Research questions • Do patients accept (undertstandable) package inserts ? • What are the effects of (understandable) package inserts ? • How can we improve patient package inserts ?

The notion “acceptance of the package insert” - Do patients read package inserts? - Are patients satisfied with package inserts ?

Do patients read package inserts ? (1) • Material • Two populations surveys (1988 and 1991) • Two registrations studies (1989 and 1990) (Van haecht et al., 1992) • Four descriptive studies in the elderly • One randomised clinical study : Technical Package Insert (TI) versus Patient Package Insert (PPI) (Van haecht et al., 1991)

Do patients read package inserts ? (2) Population surveys (interview at home) Do you read the insert when you take a medicine ? Survey 1 Survey 2 1988 (N=398) 1991 (N=402) I read the insert 89% 85% I do not read the insert, nor does another member of the family 7% 8% I do not read the insert, but another member of the family does 4% 7% TOTAL 100% 100%

Do patients read package inserts (3) Registration studies in primary care patients with hypertension (Van haecht, et al., 1992) Do you read the insert of the medicines you are currently taking ? Study 1 Study 2 1989 (N=702) 1990 (N=407) (16% PPI penetration) (39% PPI penetration) I read the insert thoroughly (recently or in the past) 36% 34% I read the insert superficially (recently or in the past) 31% 31% I never read the insert 33% 35% TOTAL 100% 100%

Do patients read package inserts ? (4) Studies in active and fragile elderly, living at home Do you read the insert when you take a medicine ? Active elderly Fragile elderly (N=93) (N=400) I read the insert 69% 62% I do not read the insert, nor does somebody else. 29% 1% I do not read the insert, but somebody else does 2% 37% TOTAL 100% 100%

Do patients read package inserts ? (5) Studies with elderly in institutional care Elderly in nursing homes (N=198) The insert is no longer distributed to the resident but is read and often kept by the nurses). Elderly in subacute geriatric hospital care (N=224) Despite important changes in the medication list, little information is given during hospital stay and at discharge. Medication given at discharge is not accompanied with written drug information.

Do patients read package inserts ? (6) Randomised clinical trial: Technical Package Insert (TI) versus Patient Package insert (PPI) with strong analgesics used in acute, benign trauma of muscles or joints (N=366) (Van haecht et al., 1991) Did you read the insert ? TI PPI (n=156) (n=161) I have read the insert thoroughly 24% 32% I have read the insert superficially 45% 41% I have not read the insert 31% 27% TOTAL 100% 100%

Are patients satisfied with package inserts ?(1) Material • Population survey of the acceptance of technical package inserts in 1989 (N=398) • Randomised clinical trial : Technical Package Insert (TI) versus Patient Package insert (PPI) (Van haecht et al., 1991)

Are patients satisfied with package inserts ?(2) Survey of technical package inserts (TIs) in 1989 (N=398) • % respondents (moderately) agree with the statement : • The package insert : • is useful (89%), is complete (71%) • is difficult to understand (57%), is difficult to remember (52%) • is difficult to read (45%) • makes one fearful to take the medicine (31%) • deminishes the confidence in the physician (25%)

Are patients satisfied with package inserts ?(3) Randomised clinical trial : Technical Package Insert (TI) versus Patient Package Insert (PPI) with strong analgesics used in acute, benign trauma of muscles or joints (N=366) (Van haecht et al., 1991) In both arms of the study the readers of the insert were satisfied with the insert and found the insert useful. The difference in style between the two types of inserts was perceived: More readers of Patient Package inserts perceived the insert as understandable More readers of Technical Package Inserts perceived the insert as vague

Effects of the insert on behavior • impact on patient complience • impact on minimising risks Effects of the insert on cognition • impact on knowledge • impact on benefit/risk perception Effects on outcomes

Is there effect of inserts on behavior ? • Study of the literature • Little impact on patient compliance • Little evidence available on impact on minisation of risks. • Three randomised clinical trials • More sponteaneous reporting of health problems, attributed to the drug (Van haecht et al., 1991) • A trend indicating impact on patient compliance (measured with electronic monitoring, but undecided because of problems with bias and recruitment in two trials.

Is there impact of the insert on knowlegde ? The conclusion of the literature is : The proces of reading understandable written information has an positive influence on the level of knowledge about medicines among patients (from a very low level to a reasonable level). (Morris et al., 1979). This was confirmed by our experimental psychology study (see further)

Impact on risk/benefit perception ? (1) • Randomised clinical trial: Technical Package Insert (TI) versus Patient Package Insert (PPI) (Van haecht et al., 1991) • In the group of readers of the PPI a slight but significant deterioration of the balance in benefit/risk perception was observed. • Experimental psychology study: Patient Package Inserts with or without a benefit message • see further

How can we improve patient package inserts ? • By making linguistic improvements • See “multilingual medical glossary” on the web • By improving the graphical design • By testing inserts more thoroughly • Computerised readability tests • Field tests of the impact • By adding a benefit message to the insert

Impact of the benefit message (1)

Impact of the benefit message (2) Nature of the study Experimental psychology study among healthy volunteers Interventie Reading a Patient Package Insert (PPI) with a benefit message compared to - reading a normal PPI - a control group with no information

Impact of the benefit message (3) • Three different clinical situations • Cisapride for benign gastric motility disorders • Itraconazol for fungus infection of the toe nail • Risperdon in chronic psychosis • Three exeperimental groups. • Control group (CON) Was asked to read a control text of 900 words, with content not related to medicines. • Intervention group 1: (PPI)Was asked to read a normal, but well written understandable patient package insert of 800 tot 1000 words. • interventiegroep 2: (BEN) Was asked to read the same PPI, but with a benefit message paragraph included (80-100 words extra)

Impact of the benefit message (4) Design Reading of the scenario CON 90 healthy volunteers R PPI Random-isation BEN Intervention: Reading text Test taking

Cisapride for benign gastric motility disorders In normal digestion ingested food flows in one direction from the mouth to the stomach and then to the guts. Little muscles at the entrance and at the exit of the stomach keep the food from flowing back. Other muscles inside the stomach and in the guts mould the food and push it further. [Cisapride] helps these little muscles to work well together. This favours a good digestion.

Itraconazol for toe nail infection A fungus can cause infection of one or more toe nails. [Itraconazol] stops the growth of the fungus and kills it. When the fungus is killed by [itraconazol], a healthy nail will grow back. The natural healing process takes time. Therefore, the signs of infection can still be present for a while. It can take several months before the nail looks completely healthy.

Risperidon in chronic psychosis Psychosis is a mental disease, in which the working of the brain is disturbed as to thinking, feeling and acting. The symptoms can be: confusion, hallucination, distortions in hearing and sight, paranoia, feelings of anxiety and tension. [Risperidone] relieves the symptoms of chronic psychosis and helps to restore normal functioning in society. In most cases the medicine needs to be taken for a long time continuously, to suppress the signs of the disease. When treatment is stopped, the symptoms can return.

Impact of the benefit message (5) Test material • Knowledge test • 20 simple questions • Possible answers : • Yes / No / I do not know • An assessment scale for benefit/risk perception

Impact of the benefit message (6) Measurement of benefit/risk perception of medicines by patients with a 5 point Likert scale. The advantages of this medicine are bigger than its disadvantages. Strongly Moderately Neutral Moderately Strongly agree agree disagree disagree } Procent agree

Impact of the benefit message (7) Results of the knowledge test Number of correct answers to 20 questions 20 16 * * 12 * 8 * Differrence CON versus PPI and BEN p<0.05 Wilcoxon 4 0 CON PPI BEN CON PPI BEN CON PPI BEN CIS ITR RIS

Impact of the benefit message (8) Results of benefit/risk perception assessment % agree with statement : The advantages of this medicine are bigger than its disadvantages. 100% * 84 ** 80% ** 70 * Difference l CON - PPI p<0.05 CHI² ** * 64 62 62 60% 54 41 40% 36 31 ** Differencel PPI - BEN p<0.05 CHI² 20% 0% CON PPI BEN CON PPI BEN CON PPI BEN CIS ITR RIS

General discussion • The studies presented here : • are mostly of small sample sizez and often limited as to generalisation. • have been performed over a period of 15 years. • were conducted in Belgium (mostly Flanders) • had as object the “perception of the patient”, which is difficult to measure.

Conclusions on impact of inserts • Patient Package Inserts are accepted by patients • PPIs are read by the majority of patients • PPIs contribute to patient satisfaction • Patient Package Inserts have an impact • PPIs raise the level of knowledge on medicines • PPIs stimulate the spontanuous reporting of unwanted effects. • PPIs influence benefit/risk perception PPIs earn their place in modern drug distribution systems.

Conclusions on benefit/risk perception • Benefit/risk perception is an important element in the processing of information on medicines. • More comprehension of the cognitive aspects of the impact of patient package inserts is necessary to : • understand the relation between drug information and patient behavior • be able to write better inserts.

Conclusions on the quality of inserts. • Much can be done to further improve patient package inserts • Among writers of the patient package insert more attention should be given to the educational function of this communication instrument • It is worthwhile to further persue the study of the value of a benefit message in the patient package insert.

L’homme a inventé la parole pour cacher ses idées (man has invented words to hide his thougths) Prince De Talleyrand Science must be explained as simple as possible, but not simpler Albert Einstein

Dr. R. Vander Stichele Department of Pharmacology Heymans Institute of Pharmacology