1. Prescription Drug Information for Patients: History

2. 1500s: Ethical Statutes of Royal College of Physicians
“Let no physician teach the people about medicines or even tell them the names of the medicines, particularly the more potent ones … for the people may be harmed by their improper use.”
violations resulted in a 40 shilling fine

3. 1938: Federal Register Notice
Drug labeling should be written “only in such medical terms as are not likely to be understood by the ordinary individual.”

4. Culture Changed

5. 1960s – 1970s Short isoproterenol warning
Patient Package Inserts (PPIs) to be written and distributed for oral contraceptives and estrogens
directed to healthy women using drugs associated with significant health risks

6. 1980s 1980: Regulation issued for a pilot project
1982: Regulation withdrawn in favor of encouraging private sector initiatives
1982 forward: Through national patient surveys, FDA monitored oral and written information provided by physicians and pharmacists
PPIs not mandated through regulations continued to be issued
1980: 10 drug classes requiring PPIs
1982: NCPIE formed
AMA provided written patient information at low cost to physicians

7. Culture Continued to Change
Population sophistication/education
Consumer empowerment -- desire for involvement in one’s own health care
Litigious environment
Greater attention to improving outcomes and reducing risk
Aging population

8. 1990-1995 1993: OBRA ’90 requirements changed pharmacy environment
movement away from paper
Surveys showed continuing low levels of information provision
1995: Medication Guide Proposed Regulations
set goals and time frames for information provision
proposed FDA-approved information for certain Rx products
1993: explain OBRA – Omnibus Budget Reconciliation Act of 1990
increased pharmacy computerization provisions took effect in 1993
required “offer to counsel” Medicaid patients
Continuing surveys, examples of other FDA products, including pet food, for which consumers are given extensive information ….
Continuing expressed patient desire for useful information
1995: Goals/time frames for provision of private sector-produced written Rx drug patient information
plenty of details about goals later on
Medication Guides for products (drugs and biologics) that pose “serious and significant” public health concerns

9.
1996: Public Law (PL)
adopted goals and time frames for private sector to provide useful written information
mandated process for developing a private sector long-range Action Plan
limited FDA’s ability to take further regulatory steps to require a comprehensive program
1997: HHS Secretary accepts Action Plan
1996: law codified goals and laid out restrictions on regulatory action
if goals achieved, no need for mandatory FDA-approved labeling
however, if goals not achieved FDA can then consult with the public about how to achieve them
Clarify that 1997 acceptance wsa of the plan called for in the 1996 PL

10. Remaining 1990s 1998: FDA publishes Medication Guide final regulations
1999: Medication Guide regulations become effective
1999: FDA sponsors limited evaluation (8-State study) of status of information provision to give feedback to information providers
scientifically accurate, unbiased in content and tone, sufficiently specific and comprehensive, presented in an understandable and legible format readily comprehensible to consumers, timely and up-to-date, and useful
“useful” is enabling patient to use medicine properly and appropriately, receive maximum benefit, and avoid harm

11. 2000s
2001: FDA sponsors national evaluation of progress toward PL’s initial goal
allows private sector program to continue
2005: FDA issues draft guidance regarding how it assesses written patient information
2006: FDA issues final guidance
2008: FDA-sponsored evaluation of progress toward PL’s final goal for written information provision

12. Current Varieties of Prescription Drug Patient Information
FDA-Approved Patient “Labeling”
Patient Package Inserts or PPIs
Medication Guides
Consumer Medication Information (CMI)
Promotional materials
Which brings us to the present …
Clarify that CMI is “unregulated”
NOTE that promotional materials are NOT being addressed at this meeting

13. What Types of Written Information Might Patients Receive With Their Prescription?
FDA-approved and regulated:
Medication Guides (MG)
Patient Package Inserts (PPI)
Not FDA-reviewed or regulated:
Consumer Medication Information (CMI)
FDA (CDER) has a long-standing interest in assuring that patients receive useful information with their prescription medicines.

14. What Types of Written Information Might Patients Receive With Their Prescription?
FDA-approved and regulated:
Medication Guides (MG)
Patient Package Inserts (PPI)
Not FDA-reviewed or regulated:
Consumer Medication Information (CMI)

15. When is a Medication Guide required?
Primarily for outpatient prescription products.
The product must have a “serious and significant” public health concern for which patient information is necessary to ensure safe and effective use.
There are 3 “triggering criteria”

16. “triggering criteria”
A Medication Guide is required if FDA determines one or more exist:
Patient labeling could help prevent serious Adverse Events
Product has serious risks that could affect patient’s decision to use or continue to use
Patient adherence to directions is crucial to effectiveness

17. Medication Guides Usually written by manufacturers
Reviewed and approved by FDA
Becomes part of professional labeling
Distribution requirements
Manufacturer is responsible for providing sufficient numbers of Medication Guides such that each patient receives one with every new and refilled prescription
Dispenser required to provide Medication Guide with each prescription when product is dispensed

18. Medication Guide Requirements (1)
Nontechnical, understandable language
6th to 8th grade reading level
Nonpromotional in tone and content
Specific and comprehensive content that is consistent with professional labeling
10 point minimum type size

19. Medication Guide Requirements (2)
Legible and clearly presented
appropriate use of highlighting techniques
Use of white space, bolding, headers, “chunking”
Uniform order of headings/information
Specified section headings (Q & A format)

20. Medication Guide Headers (applied as appropriate)
Brand name, established name, phonetic spelling
What is the most important information I should know about [DRUG]?
What is [DRUG]?
Who should not take [DRUG]?
How should I take [DRUG]?
What should I avoid while taking [DRUG]?
What are the possible side effects of [DRUG]?
General information (specific verbatim statements)

21. Medication Guides
The Food and Drug Administration Amendments Act of 2007 (FDAAA) stated that Medication Guides developed after March 25, 2008 will be considered part of a Risk Evaluation and Mitigation Strategy (REMS) for purposes of development and evaluation.
This means that the effectiveness of a Medication Guide as a tool to mitigate the risks associated with the drug must be evaluated.

22. Assessments
An evaluation is required to assess the effectiveness of the Medication Guide as a tool to mitigate the risks associated with the product.
Manufacturer develops survey (or other mechanism) to evaluate at 18 months, 3 years, 7 years (and sometimes more often)

23. Some of the better assessments have included questions about:
Patients receipt of the Medication Guide
Patients understanding of the specific risks or safety information conveyed in the Medication Guide
understand the information
demonstrate knowledge about what to do if they experience the event

24. Some proposals where we’ve recommended revisions have included:
Patient attestation of receipt and understanding (check boxes)
Recruit selected physicians offices or pharmacies to survey patients
Use approved Medication Guide as a reference during survey
Using general population (not necessarily patients) to test materials

25. Some proposals where we’ve recommended revisions have included:
Using patients of competitor products (“potential patients”)
Reeducating patients prior to survey by providing a Medication Guide at the time they are recruited to take survey (but not at time of survey)
Allowing respondents to be eligible to participate in multiple waves of evaluation

26. Questions under consideration to facilitate consistency (in addition to specific risk questions)
Who gave you the Medication Guide?
Did you read the Medication Guide?
Did you understand what you read in the Medication Guide?
Did someone offer to explain to you the information in the Medication Guide?
Did you accept the offer?
Did you understand the explanation that was given to you?
Used to evaluate the Medication Guide for that product
Used to evaluate Medication Guides across all products (that have Medication Guides)
Some of these are probably more “nice to know” than “need to know”

27. Questions under consideration to facilitate consistency (in addition to specific risk questions)
Did or do you have any question about the Medication Guide?
How long did you keep your Medication Guide for [DRUG]?
Other than the first time you received the Medication Guide for [DRUG], did you refer back to it for any reason?
Where did you fill your prescription for [DRUG]?
Used to evaluate the Medication Guide for that product
Used to evaluate Medication Guides across all products (that have Medication Guides)
Some of these are probably more “nice to know” than “need to know”

28. What Types of Written Information Might Patients Receive With Their Prescription?
FDA-approved and regulated:
Medication Guides (MG)
Patient Package Inserts (PPI)
Not FDA-reviewed or regulated:
Consumer Medication Information (CMI)

29. Patient Package Insert (PPI)
Two kinds of PPIs:
Required PPIs for two drug categories
oral contraceptives
estrogens
“Voluntary” PPIs for other products
Content and format not covered by regulation
Manufacturers are not required to provide to dispensers
Dispensers are not required to disseminate with each prescription

30. Patient Package Insert (PPI)
Considered to be FDA-approved labeling
Generally when FDA or manufacturer considers necessary for appropriate use
Can include Patient Instructions for Use

31. Distribution of Patient Labeling
As of June , any FDA-approved patient labeling must be reprinted with or accompany professional labeling
No way to know if patients are receiving or understanding the information
any printed patient information required to be distributed to the patient … shall be reprinted at the end of the labeling.

32. What Types of Written Information Might Patients Receive With Their Prescription?
FDA-approved and regulated:
Medication Guides (MG)
Patient Package Inserts (PPI)
Not FDA-reviewed or regulated:
Consumer Medication Information (CMI)

33. Consumer Medication Information (CMI)
Printed information typically stapled to outside of or put inside pharmacy bag
Not reviewed or regulated by FDA
Developed by commercial vendors, then sold to pharmacies
not developed by drug manufacturers

34. (1996) Public Law 104-180 Required an action plan be developed
Specified goals for receipt of useful written information with new prescriptions
75% by year 2000
95% by year 2006
If goals not met, FDA could take action to regulate these materials
By the year 2000, 75% of people receiving new prescriptions would receive “useful” written patient information with their prescriptions.
The legislation called for FDA to assess the distribution and quality of the patient information to ensure that the goals are met within the specified time frames.
The law prohibited FDA from taking regulatory action specifying uniform content or format for CMI provided the private sector initiatives met the goals within the specified timeframes.

35. 1997 Action Plan - Criteria for Useful Medication Information
Essential elements of useful information developed by consensus - "Keystone criteria”
1. Scientifically Accurate
Unbiased in Content and Tone
Sufficiently Specific and Comprehensive
Presented in an Understandable and Legible Format that is Readily Comprehensible to Consumers
Timely and up-to-date
Useful - enabling patient to use medicine properly and appropriately, receive maximum benefit, and avoid harm
Action Plan for the Provision of Useful Prescription Medicine Information
The Keystone Center, an independent organization that facilitates consensus-building processes, convened a group that consisted of HCPs, Consumer organizations, voluntary health agencies, pharmaceutical manufacturers, prescription drug wholesalers, drug information database companies, CMI developers, and others

36. Setting up for Evaluating Goals
1998: FDA contracted an independent assessment of the proposed program and methodology
8-state study to test the methodology for collecting CMI
Expert Panel evaluated materials
developed 8 categories of “useful” by combining the Action Plan criteria and components

37. 8 Criteria for “Useful” (1-4)
Drug names, indications for use, and how to monitor for improvement
Contraindications and what to do if they apply
Specific directions about storage and overdose
Specific precautions and warnings
The 8 categories listed were developed by an expert panel, for FDA’s evaluation of CMI in 2000, by combining the Action Plan criteria and components.
These are the 8 criteria operationalized in the 2 National evaluations of CMI (2001, 2008)

38. 8 Criteria for “Useful” (5-8)
Symptoms of serious or frequent AEs and what to do
Certain general information, including encouraging patients to communicate with healthcare professionals, and disclaimer statements
Information that is scientifically accurate, unbiased in tone and content, and up-to-date
Information is understandable and legible format that is readily comprehensible to consumers
The 8 categories listed were developed by an expert panel, for FDA’s evaluation of CMI in 2000, by combining the Action Plan criteria and components.
These are the 8 criteria operationalized in the 2 National evaluations of CMI (2001, 2008)

39. Results of 2001 Evaluation of Year 2000 Goal
almost 90% distribution
only about 50% met the minimum criteria for usefulness
Year 2000 goal of 75% not met
This study also added a consumer evaluation, which was one of the complaints about the 1998 pilot study.

40. Guidance: Useful Written Consumer Medication Information
After 2001 study, National Council on Patient Information and Education (NCPIE) convened CMI stakeholders
Improve CMI so 2006 goal (95%) can be met
Asked FDA to give advice
2006: FDA publishes final Guidance for Consumer Medication Information (CMI)

41. Results of 2008 Evaluation of Year 2006 Goal
almost 94% distribution
only about 75% met the minimum criteria for usefulness
Year 2006 goal of 95% not met
Drs. Kimberlin and Winterstein will present on the details of the 2008 evaluation.

42. Thank you for your attention