# Presentation: 580070

## Expert and Consumer Evaluation of Consumer Medication Information (CMI) 

Carole L. Kimberlin, PhD
Almut G. Winterstein, PhD

*Carole L. Kimberlin, PhD*
*Almut G. Winterstein, PhD*

## RESEARCH QUESTIONS

- What percentage of shoppers filling prescriptions were given *any* written CMI beyond label directions?
- What percentage of CMI adhered to quality criteria as determined by a national panel of pharmacy experts?
- What percentage of CMI adhered to criteria consumers were asked to use to evaluate quality of the leaflets?
- How did expert and consumer evaluations of the quality of CMI differ in the 2001 and 2008 studies?

## METHODS OVERVIEW

- Two study medications – lisinopril and metformin
- National Association of Boards of Pharmacy purchased electronic list of retail pharmacies
- Sample of 420 pharmacies selected using random selection procedure
- Subcontractor (Second to None) hired professional shoppers to pose as patients and present 2 prescriptions

## METHODS (CONT.)

- Shoppers trained to use standard protocol for playing patient role and answering questions in pharmacies
- Physicians recruited by FDA and located near sampled pharmacies wrote prescriptions
- All written material dispensed in pharmacies sent to UF
- UF conducted expert and consumer evaluations of CMI

## EXPERT EVALUATION FORM (EEF)

- Four clinical experts from UF and Shands Hospital formed Development Expert Panel
- Reviewed Standards/Criteria from 2001 evaluation and 2006 FDA Guidance document on useful CMI
- Examined FDA approved labeling for study drugs and monographs (and if available patient information monographs) in all other standard drug compendia
- Developed explicit criteria to operationally define CMI standards for the 2 drugs

## STANDARDS FOR USEFUL CMI

- Include drug names and indications
- Include contraindications and what to do if applicable
- Include specific directions about how to use, monitor, and get most benefit
- Include specific precautions and how to avoid harm while using it
- Include symptoms of serious or frequent adverse reactions and what to do
- Include general information and encouragment to ask questions
- Be scientifically accurate, unbiased, and up-to-date
- Be readily comprehensible and legible

- Content

- Format

## NATIONAL EXPERT PANEL

- Eight pharmacy experts
- Reviewed and modified EEF
- 40 CMI rated independently by pairs to determine inter-rater reliability and modify content as needed
- Inter-rater reliability checks continued during data collection

## SCORING PROCEDURES

- Criteria 1-6:Raters indicated whether each item of information identified for each subcriterion was present or not
- Criterion 7: Raters evaluated scientific accuracy
- Criterion 8: Format
- Expert panel assessed four of the readability criteria
- Staff assessed explicit measures such as font size, amount of white space around text, line length, use of bullets, reading level

## SCORING PROCEDURES (CONT.)

- Adherence of CMI to criteria reported as a percent of total possible points obtained for:
- Overall aggregate score
- For each individual general criterion (1-8)
- For each individual subcriterion
- Means and standard deviations / 95% confidence intervals for aggregate and general criteria reported

## SCORING PROCEDURES (CONT.)

- Frequency distributions reflecting six levels of adherence  (used to compare to 2001 findings)
- Level 0: no written information provided
- Level 1: information included 0-19% of subcriteria
- Level 2: information included 20-39% of subcriteria
- Level 3: information included 40-59% of subcriteria
- Level 4: information included 60-79% of subcriteria
- Level 5: information included 80-100% of subcriteria

## CONSUMER EVALUATION FORM

- Developed by Svarstad and Mount and used in 2001 study.
- 5 point semantic differential scale – low scores = low quality
- First 9 items ask how consumer would feel about leaflet if taking medicine for 1st time
- Remaining three items – overall opinion about readability, comprehensibility and usefulness of leaflet
- Responses for all items summated and reported as average percent and standard deviation of possible points along with 5-level frequency distributions obtained to compare to 2001

## RECRUITMENT OF CONSUMER EVALUATORS

- 14 site coordinators in 13 states
- Recruited 12-20 consumers each
- All materials approved by UF IRB and local IRBs for site coordinators
- Snowball recruitment from clinics, churches, apartments, organizations
- Consumers had to
- Read CMI in English
- Have no training as health professional
- Not have diabetes or hypertension or have taken medications in same class as study drugs

## RESULTS

- 365 pharmacies dispensed prescriptions for study drugs (1 pharmacy only dispensed for lisinopril)
- 22 (6%) – no CMI for either lisinopril or metformin
- CMI ranged from 33 words to 2,482 words
- Publishers of content
- No publisher identified – 43%
- Of remainder:
- 		56% First Databank
- 		42% Wolters Kluwer Health
- 		  2% Other

## RESULTS – OVERALL QUALITY OF CMI

**Figure: Frequency of CMI Quality  for Lisinopril (n=365) and Metformin (n=364)**

## RESULTS –QUALITY OF CMI PER CRITERION

**Figure: Mean Quality  of Dispensed CMI**

## COMPARISON TO 2001

|  | 2001 | 2006 |
| --- | --- | --- |
| Cat 1 (Indication) | 43% | 68% |
| Cat 2 (CI) | 33% | 82% |
| Cat 3 (Directions) | 67% | 31% |
| Cat 4 (Precautions) | 21% | 80% |
| Cat 5 (ADRs) | 27% | 84% |
| Cat 6 (General) | 18% | 61% |
| Cat 7 (Accuracy) | 98% | 97% |
| Cat 8 (Format) | 18% | 8% |

**Percent dispensed CMI that met >=60% of Expert Quality Criteria**

## HIGHS AND LOWS IN CATEGORY 3: "DIRECTIONS"

|  | Lisinopril |
| --- | --- |
| Action: ask about lab tests | 8% |
| Frequency of tests | 13% |
| Action: ask about BP readings / self-monitor | 18% |
| Overdose symptoms | 32% |
| Phone number of poison control center | 32% |
|  |  |
| Administration with our without food | 91% |

|  | Metformin |
| --- | --- |
| Action: ask about lab tests | 0% |
| Vitamin B12 monitoring | 1% |
| Frequency of lab tests | 5% |
| Monitoring schedule for HbA1c | 9% |
| Phone number of poison control center | 17% |
|  |  |
| Administration with food | 91% |

## HIGHS AND LOWS IN CATEGORY 8: "FORMAT"

|  | Lisinopril |
| --- | --- |
| Black box warning in bold or box | 3% |
| Bolded text used for emphasis | 5% |
| Bullets used to enhance readibility | 7% |
| Written at ≤ 8th grade reading level | 10% |
| Space between lines ≥ 2.2 mm | 15% |
|  |  |
| Upper and lower case lettering | 99% |
| Minimal use of italics or ornate typeface | 99% |
| Good ink-paper contrast | 97% |
| Limited use of medical / technical terms | 94% |

## OTHER LOW SCORES

|  | Lisinopril | Metformin |
| --- | --- | --- |
| Angioedema can be fatal | 2% |  |
| Action for serious side effect: don’t take drug | 3% | 18% |
| Physical description of drug or imprint code | 45% | 39% |
| Other precautions: leucopenia, neutropenia | 41% |  |
| Date of publication | 51% | 48% |
| Brand names | 39% | 37% |
| Contraindicated: contrast agent |  | 40% |
| Usual dosing  | 38% | 34% |

## RESULTS – PHARMACY OWNERSHIP AND EXPERT-RATED QUALITY

| Lisinopril | Independent  | Chain |
| --- | --- | --- |
| Overall Quality* | 55.1 ±20.3 | 70.0 ±9.3 |
| Content* | 53.0 ±28.7 | 75.1 ±12.4 |
| Format* | 49.6 ±10.1 | 41.8 ±10.8 |
| Word Count* | 856 ±546 | 1314 ±316 |

| Metformin | Independent  | Chain |
| --- | --- | --- |
| Overall Quality* | 52.1 ±20.1 | 65.8 ±9.9 |
| Content* | 49.0 ±28.1 | 70.1 ±12.8 |
| Format* | 49.5 ±10.5 | 40.2 ±10.5 |
| Word Count* | 978 ±677 | 1553 ±401 |

- * p<0.05

## RESULTS – CONSUMER-RATED QUALITY OF CMI

**Figure: Frequency of CMI Quality  for Lisinopril (n=343) and Metformin (n=342)**

## COMPARISON OF CONSUMER-RATED QUALITY TO 2001

|  | Level 1 (<20%) | Level 2 (<40%) | Level 3 (<60%) | Level 4 (<80%) | Level 5 (<100%) |
| --- | --- | --- | --- | --- | --- |
| 2001 
(n=1,236) | 7.9 | 14.8 | 21.0 | 30.9 | 25.4 |
| 2008 (n=685) | 0 | 3.8 | 25.1 | 47.0 | 24.1 |

## ARE SOME PUBLISHERS BETTER?

- No noteworthy difference in overall quality, content or format quality
- Significant variability of leaflets within one publisher

## FIRST DATA BANK I

## FIRST DATA BANK II

## Slide 26

## WOLTERS I

## WOLTERS II

## HOW DO PUBLISHERS SELECT INFORMATION FOR CMI?

*Macrovascular Outcomes—There have been no clinical studies establishing conclusive *evidence of macrovascular risk reduction with GLUCOPHAGE or GLUCOPHAGE XR or any other anti-diabetic drug. *Monitoring of renal function—Metformin is known to be substantially excreted by the *kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Thus, patients with serum creatinine levels above the upper limit of normal for their age should not receive GLUCOPHAGE or GLUCOPHAGE XR. In patients with advanced age, GLUCOPHAGE and GLUCOPHAGE XR should be carefully titrated to establish the minimum dose for adequate glycemic effect, because aging is associated with reduced renal function. In elderly patients, particularly those ≥80 years of age, renal function should be monitored regularly and, generally, GLUCOPHAGE and GLUCOPHAGE XR should not be titrated to the maximum dose (see **WARNINGS and DOSAGE AND ADMINISTRATION). **Before initiation of GLUCOPHAGE or GLUCOPHAGE XR therapy and at least annually thereafter, renal function should be assessed and verified as normal. In patients in whom development of renal dysfunction is anticipated, renal function should be assessed more frequently and GLUCOPHAGE or GLUCOPHAGE XR discontinued if evidence of renal impairment is present. *Use of concomitant medications that may affect renal function or metformin disposition— *Concomitant medication(s) that may affect renal function or result in significant hemodynamic change or may interfere with the disposition of metformin, such as cationic drugs that are eliminated by renal tubular secretion (see **PRECAUTIONS: Drug Interactions), should be used with caution. **21 *Radiologic studies involving the use of intravascular iodinated contrast materials (for example, intravenous urogram, intravenous cholangiography, angiography, and computed tomography (CT) scans with intravascular contrast materials)—Intravascular *contrast studies with iodinated materials can lead to acute alteration of renal function and have been associated with lactic acidosis in patients receiving metformin (see **CONTRAINDICATIONS). Therefore, in patients in whom any such study is planned, **GLUCOPHAGE or GLUCOPHAGE XR should be temporarily discontinued at the time of or prior to the procedure, and withheld for 48 hours subsequent to the procedure and reinstituted only after renal function has been re-evaluated and found to be normal. *Hypoxic states—Cardiovascular collapse (shock) from whatever cause, acute congestive *heart failure, acute myocardial infarction and other conditions characterized by hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia. When such events occur in patients on GLUCOPHAGE or GLUCOPHAGE XR therapy, the drug should be promptly discontinued. *Surgical procedures—GLUCOPHAGE or GLUCOPHAGE XR therapy should be *temporarily suspended for any surgical procedure (except minor procedures not associated with restricted intake of food and fluids) and should not be restarted until the patient’s oral intake has resumed and renal function has been evaluated as normal. *Alcohol intake—Alcohol is known to potentiate the effect of metformin on lactate *metabolism. Patients, therefore, should be warned against excessive alcohol intake, acute or chronic, while receiving GLUCOPHAGE or GLUCOPHAGE XR. *Impaired hepatic function—Since impaired hepatic function has been associated with *some cases of lactic acidosis, GLUCOPHAGE and GLUCOPHAGE XR should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. *Vitamin B12 levels—In controlled clinical trials of GLUCOPHAGE of 29 weeks duration, *a decrease to subnormal levels of previously normal serum vitamin B12 levels, without clinical manifestations, was observed in approximately 7% of patients. Such decrease, possibly due to interference with B12 absorption from the B12-intrinsic factor complex, is, however, very rarely associated with anemia and appears to be rapidly reversible with discontinuation of GLUCOPHAGE or vitamin B12 supplementation. Measurement of hematologic parameters on an annual basis is advised in patients on GLUCOPHAGE or GLUCOPHAGE XR and any apparent abnormalities should be appropriately investigated and managed (see **PRECAUTIONS: Laboratory Tests). **22 Certain individuals (those with inadequate vitamin B12 or calcium intake or absorption) appear to be predisposed to developing subnormal vitamin B12 levels. In these patients, routine serum vitamin B12 measurements at two- to three-year intervals may be useful. *Change in clinical status of patients with previously controlled type 2 diabetes—A patient *with type 2 diabetes previously well controlled on GLUCOPHAGE or GLUCOPHAGE XR who develops laboratory abnormalities or clinical illness (especially vague and poorly defined illness) should be evaluated promptly for evidence of ketoacidosis or lactic acidosis. Evaluation should include serum electrolytes and ketones, blood glucose and, if indicated, blood pH, lactate, pyruvate, and metformin levels. If acidosis of either form occurs, GLUCOPHAGE or GLUCOPHAGE XR must be stopped immediately and other appropriate corrective measures initiated (see also **WARNINGS). ***Hypoglycemia—Hypoglycemia does not occur in patients receiving GLUCOPHAGE or *GLUCOPHAGE XR alone under usual circumstances of use, but could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents (such as sulfonylureas and insulin) or ethanol. Elderly, debilitated, or malnourished patients, and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects. Hypoglycemia may be difficult to recognize in the elderly, and in people who are taking beta-adrenergic blocking drugs. *Loss of control of blood glucose—When a patient stabilized on any diabetic regimen is *exposed to stress such as fever, trauma, infection, or surgery, a temporary loss of glycemic control may occur. At such times, it may be necessary to withhold GLUCOPHAGE or GLUCOPHAGE XR and temporarily administer insulin. GLUCOPHAGE or GLUCOPHAGE XR may be reinstituted after the acute episode is resolved. The effectiveness of oral antidiabetic drugs in lowering blood glucose to a targeted level decreases in many patients over a period of time. This phenomenon, which may be due to progression of the underlying disease or to diminished responsiveness to the drug, is known as secondary failure, to distinguish it from primary failure in which the drug is ineffective during initial therapy. Should secondary failure occur with either GLUCOPHAGE or GLUCOPHAGE XR or sulfonylurea monotherapy, combined therapy with GLUCOPHAGE or GLUCOPHAGE XR and sulfonylurea may result in a 23 response. Should secondary failure occur with combined GLUCOPHAGE/sulfonylurea therapy or GLUCOPHAGE XR/sulfonylurea therapy, it may be necessary to consider therapeutic alternatives including initiation of insulin therapy.

- Volume – what is the right amount?
- Leaflets were rated based on presence of information, not efficiency or prioritizing of information
- The more the better

## Slide 31

## Slide 32

## WORD EFFICIENCY

- Word count distribution of leaflets with content quality >80%
- 			**Lisinopril****	****	****Metformin**
- Average 		 1523			    1918
- Minimum	 1112			    1462
- Maximum	 2106			    2482

## CONTENT QUALITY AND WORD COUNT

- Regression of word count on content quality for lisinopril and metformin (for quadratic relationship R2>0.75)

- Format – how to organize and present the information

## Slide 39

- Distractors – how to maintain focus on critical information

## Slide 42

## DISCUSSION – RESEARCH AGENDA SURROUNDING CMI

- Data Warehouse

- Pharmacy

- Patient

- Hand-over with or without verbal counseling

- Modifications (content/format)? Updates?
- Individualized / individualizable?
- Disclaimers?

- Selection criteria for content?
- Patient relevance?
- Updates?
- Format?

- How do patients use leaflets (eg. PRN or before medication use)?
- Determinants of comprehension?

- What is the evidence base for labeling information?

## PROPOSED FUTURE RESEARCH QUESTIONS

- What information in the label is clinically significant?
- What criteria for CMI content selection should be used?
- Clinical significance/severity
- Prevalence
- Importance for self management
- Relevance to individual patient
- Legal protection
- Are there better media than a leaflet?
- How does verbal counseling during dispensing change the usefulness of CMI?
- How does any of the above affect comprehension and patient ability to make informed decisions regarding medication use?