CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`
`
`APPLICATION NUMBER:
`22-272
`
`
`RISK ASSESSMENT and RISK MITIGATION
`REVIEW(S)
`
`
`
`
`
`
`

`

`
`
`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Surveillance and Epidemiology
`
`June 18, 2010
`
`Bob Rappaport, MD, Director
`Division of Anesthesia and Analgesia Products (DAAP)
`
`Mary Willy, MPH, Deputy Director
`Division of Risk Management (DRISK)
`Gita A. Toyserkani, Pharm.D., MBA, Senior Drug Risk
`Management Analyst, Acting TL
`Mary Dempsey BS, Coordinator for Risk Management
`Programs, DRISK
`
`Prior Approval REMS Modification
`
`OxyContin Tablets
`(oxycodone hydrochloride controlled-release)
`NDA 022272
`Purdue Pharma L.P.
`2010-1354
`
`Date:
`
`To:
`
`Through:
`
`From:
`
`Subject:
`
`Drug Name(s):
`
`Application Type:
`Applicant/sponsor:
`OSE RCM #:
`
`
`
` 1
`
` Background
`The Division of Anesthesia and Analgesia Products (DAAP) requested that the Division
`of Risk Management (DRISK) review the OxyContin (oxycodone hydrochloride
`controlled-release) tablets Prior Approval REMS Modification Supplement for New Drug
`Application (NDA 022272) submitted by Purdue Pharma L.P. on June 10, 2010. This
`supplemental new drug application provides for revisions to the Training Guide for
`Healthcare Providers, boxed warning, table of contents, references, removal of website
`reference, and upper/lower case text.
`
`

`

`The OxyContin (oxycodone hydrochloride controlled-release) tablets REMS was
`approved April 5, 2010 with the following elements:
`• Medication Guide
`• Elements to Assure Safe Use
`o Healthcare provider training
`o Dear Healthcare Professional letter mailed at least three (3) weeks prior to
`first availability of Oxycontin
`o Prescriber re-training every two (2) years
`• Timetable for Submission of Assessment
`
`
`
`
`2 Material Reviewed
`• April 2, 2010 Purdue submitted REMS Supporting Document
`• April 5, 2010 Oxycontin REMS approval
`June 10, 2010 Purdue submitted Prior Approval REMS Modification
`•
`
` 3
`
` Proposed REMS Elements
`The Oxycontin June 10, 2010 submission provides the proposed REMS modification,
`Medication Guide, Dear Healthcare Professional Letter, Healthcare Provider Training
`Guide, and Education Confirmation Form. The REMS Supporting Document is not
`included in this submission. The product is in pre-launch development and not currently
`marketed; therefore, it is reasonable to state that insufficient time has passed since the
`REMS approval to provide a meaningful assessment. The cover letter of the June 10,
`2010 submission states the following:
`
`
`
`
`
`“The approved REMS Supporting Document remains unchanged and is identical
`to the version submitted on April 2, 2010
`
`Herein we are submitting the revised REMS…which include revisions only to the
`Training Guide for Healthcare Providers. In our view, these revisions are minor
`and do not change the content, but rather improve the document quality. For ease
`of review, the revisions are outlined below:
`“(oxycontin hydrochloride controlled release) added to headline page and the
`•
`indication pg 4
`• Boxed warning from approved FPI replaced current version that was
`developed for use in HCP Guide. This ensures that a consistent official black
`box warning is used in the FPI and Training Guide [this is the only one that
`should be in circulation]
`“Full Prescribing “ and Boxed Warning- Uppercased throughout the document
`
`•
`
`
`
`
`
`2
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`

`

`• Table of Contents (TOC moved to page 3 after black boxed warning, This
`ensures that the TOC precedes the Introduction section, rather than after the
`Introduction where it is currently located
`• Removed reference to website on page 11 as not relevant to section
`• References reordered to be in numerical sequence (previously jumped from #1
`to # 7).”
`
`
`
`
`
` 4
`
` Discussion and Conclusion
`DRISK performed a comparison of the June 10, 2010 submitted proposed REMS and
`Medication Guide to the approved Oxycontin REMS and Medication Guide and found
`then to be identical. The revisions to the Healthcare Provider Training Guide proposed
`by Purdue are acceptable.
`
`
`5. Recommendation
`Approve the REMS modification as submitted June 10, 2010.
`
`
`
`
`
`3
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`

`

`Application
`Type/Number
`--------------------
`NDA-22272
`
`Submission
`Type/Number
`--------------------
`SUPPL-5
`
`Submitter Name
`
`Product Name
`
`--------------------
`PURDUE PHARMA
`INC
`
`------------------------------------------
`OXYCONTIN
`
`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`MARY J DEMPSEY
`06/18/2010
`
`MARY E WILLY
`06/19/2010
`I concur
`
`

`

`
`
`Department of Health and Human Services
`Public Health Service
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Surveillance and Epidemiology
`
`
`
`April 2, 2010
`
`Bob Rappaport, MD, Director
`Division of Anesthesia and Analgesia Products (DAAP)
`Claudia Karwoski, Pharm.D., Director
`Division of Risk Management (DRISK)
`
`Scientific Lead:
`Jeanne Perla, Ph.D., Risk Management Analyst
`
`Team Members:
`DRISK
`Marcia Britt, Ph.D., Health Education Reviewer
`Brian Gordon, MA, Social Science Reviewer
`Sharon Mills, BSN, RN, CCRP, Patient Product Information
`Reviewer Acting Team Leader
`Gita Toyserkani, Pharm.D., MBA, Acting Team Leader
`
`Division of Pharmacovigilance II
`Afrouz Nayernama, Pharm.D., Safety Evaluator
`
`Division of Medication Error Prevention and Analysis
`Kristina Arnwine, Pharm.D., Safety Evaluator
`
`Division of Drug Marketing, Advertising and Communication
`Mathilda Fienkeng, Pharm.D., Regulatory Review Officer
`Twyla Thompson, Pharm.D., Regulatory Review Officer
`
`Office of Compliance Division of Risk Management and
`Surveillance
`Agnes Plante, BSN, RN, Consumer Safety Officer
`Review of Risk Evaluation and Mitigation Strategy (REMS)
`OxyContin® (oxycodone hydrochloride controlled-release)
`NDA 22-272
`
`Purdue Pharma Inc
`RCM: 2009-788
`
`
`
`1
`
`Date:
`To:
`
`Thru:
`
`From:
`
`Subject:
`Drug Name(s):
`Application
`Type/Number:
`Applicant/sponsor:
`OSE RCM #:
`
`
`
`

`

`
`
`EXECUTIVE SUMMARY
`OxyContin® (oxycodone hydrochloride controlled-release) is an opioid analgesic with the
`proposed indication for the management of moderate to severe chronic pain when a
`continuous, around-the-clock opioid analgesia is needed for an extended period of time.
`The Sponsor submitted a proposed Risk Minimization Action Plan (RiskMAP) on
`November 29, 2007, during the first review cycle. In accordance with section 505-1 of
`the FDCA, the Agency determined that a REMS is necessary for OxyContin® to ensure
`that the benefits of the drug outweigh the risks of abuse, misuse, and overdose. The
`Sponsor was officially notified of this requirement on June 17, 2009.
`The Agency has been considering REMS elements that should be implemented for a
`number of opioid products, including modified-release opioids, to address the risks of
`abuse, misuse, and overdose. A class REMS for long-acting and high potency opioids is
`also being considered. Until the Agency has determined the elements or possibly a class-
`wide REMS, DAAP with input from OSE, has decided that an interim REMS for long-
`acting and high potency opioids will be required as these products are approved.
`The Sponsor submitted an interim REMS to address the risks of abuse, misuse, overdose,
`and addiction on March 24, 2010. The REMS includes a Medication Guide, Element to
`Assure Safe Use, specifically a plan to ensure Healthcare providers who prescribe
`OxyContin® will receive training under 505-1(f)(3)(A), and a timetable for submission of
`assessment of the REMS. We find the proposed REMS submitted on March 24, 2010, to
`be acceptable.
`Once the elements of the class-wide opioid REMS are determined, the Sponsor will be
`notified to resubmit a REMS incorporating these elements, as was conveyed to the
`Sponsor in the June 17, 2009 Information Request letter.
`
`1 BACKGROUND
`
`1.1 INTRODUCTION
`The proposed indication for OxyContin® is for the management of moderate to severe
`chronic pain in patients requiring continuous, around-the-clock opioid analgesia for an
`extended period of time. OxyContin® tablets are manufactured in 10 mg, 15 mg, 20 mg,
`30 mg, 40 mg, 60 mg and 80 mg dosage strengths. A single dose of OxyContin® greater
`than 40 mg, or a total daily dose greater than 80 mg are only for use in opioid-tolerant
`patients to avoid fatal respiratory depression. OxyContin® must not be cut, broken,
`chewed, crushed, or dissolved. Doing so can lead to rapid release and absorption of a
`potentially fatal dose of oxycodone. The clinical review of the clinical trials did not
`identify any unexpected adverse events, but did find the typical opioid-related adverse
`events.
`A joint meeting of the Anesthetic and Life Support Drugs Advisory Committee and the
`Drug Safety and Risk Management Advisory committee was held on September 24,
`2009. The joint committee was asked to discuss a) whether the studies performed by the
`sponsor adequately characterize the physical attributes of the reformulated OxyContin®
`product, b) whether the change in formulation affects the overall safety profile of
`
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`
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`OxyContin® and c) whether this application for a reformulated OxyContin® should be
`approved.
`
`The advisory panel consensus was that studies performed by the sponsor did adequately
`characterize the physical attributes of the reformulated OxyContin® product; however,
`many members expressed major concern with the lack of detail in the data presented by
`the sponsor. After discussing the effects of the change in formulation on overall safety,
`fourteen members voted to approve, four members voted not to approve, and one member
`abstained.
`
`1.2 REGULATORY HISTORY
`FDA approved OxyContin® Tablets (NDA 20-553), a controlled-release oral formulation
`of oxycodone hydrochloride on December 12, 1995. Due to the ongoing public health
`concerns indicating abuse and diversion of the current approved formulation of
`OxyContin®, FDA and Purdue discussed the development of an abuse deterrent/abuse
`resistant formulation of OxyContin®.
`The sponsor submitted a RiskMAP on November 29, 2007 with the original NDA
`application for the reformulated OxyContin® product. A Complete Response (CR) letter
`was sent to the Sponsor on October 3, 2008 because the agency had determined that a
`Risk Evaluation and Mitigation Strategy (REMS) was necessary and in the CR letter a
`detailed description of the required elements of the proposed REMS were provided.
`During the review of this NDA, the Agency was considering implementing a REMS
`across the class of modified-release opioids to address the risks of abuse and overdose
`and use in non-opioid tolerant individuals. Therefore, on December 4, 2008 the sponsor
`was sent a letter requesting that the sponsor not submit a Risk Evaluation and Mitigation
`Strategy (REMS) until the Agency notified the sponsor in writing about the elements
`necessary for a REMS across the class of modified-release opioids and that the Sponsor
`would be notified once that determination was made. .
`
`On June 17, 2009, a General Correspondence Letter was sent to the Sponsor informing
`them that a class REMS for modified-released opioids would be implemented in the
`future. Until such a REMS was approved, Purdue Pharma was to submit a REMS that
`comprised of a Medication Guide, a Communication Plan, and a timetable for submission
`of assessments. The letter stated that once the elements of the class-wide REMS were
`determined, the sponsor would be required to submit a REMS incorporating these
`elements.
`On July 23, 2009 (and amended on September 18, 2009 and November 13, 2009), Purdue
`submitted a proposed REMS in response to the general correspondence letter. After
`reviewing the proposed REMS and upon further consideration, the Agency determined
`that a Medication Guide and communication plan would not be adequate to ensure
`adequate training of healthcare providers to address the risks of abuse, misuse, and
`overdose. Therefore, on December 11, 2009, Purdue was notified that the REMS for
`OxyContin® (oxycodone hydrochloride controlled-release) must contain an element to
`assure safe use, specifically healthcare provider training under 505-1(f)(3)(A), to ensure
`that the benefits of OxyContin® (oxycodone hydrochloride controlled-release) outweigh
`
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`the risks. Subsequently, the Sponsor submitted proposed REMS amendments on
`December 21, 2009, February 4, 2010, and March 24, 2010.
`
`2 MATERIAL REVIEWED
`
`2.1 DATA AND INFORMATION SOURCES
`1. General Correspondence Letter sent June 17, 2009
`2. Proposed REMS submitted July 23, 2009
`3. Proposed REMS amendment, submitted September 18, 2009
`4. REMS notification letter sent December 11, 2009
`5. Proposed REMS amendment (in response to REMS notification letter), submitted
`December 21, 2009.
`6. Proposed REMS amendment, submitted February 4, 2010.
`7. Proposed REMS amendment, with final REMS proposal submitted March 24, 2010.
`
`2.2 ANALYSIS TECHNIQUES
`
`The submission was reviewed for conformance with Title IX, Subtitle A, Section 901 of
`the Food Drug Administration Amendments Act of 2007 (FDAAA) and the elements
`outlined in the REMS Notification Letter, as well as responsiveness to comments
`submitted to the Sponsor as part of the ongoing review.
`
`3
`
`RESULTS OF REVIEW
`
`3.1 SAFETY CONCERNS
`Safety concerns identified by the sponsor, DAAP and OSE are the potential for abuse,
`misuse, overdose, and addiction of OxyContin®, as well as the risk of use of OxyContin®
`60 mg and 80 mg tablets, or doses great than 40 mg, in non-opioid-tolerant individuals.
`
`3.2 PROPOSED REMS
`The March 24, 2010 final proposed REMS submission contains the following:
`3.2.1 Goals:
`1. To inform patients and healthcare professionals about the potential for abuse,
` misuse, overdose, and addiction of OxyContin®
`2. To inform patients and healthcare professionals about the safe use of
` OxyContin®
`
`3.2.2 Medication Guide (MG)
`In accordance with 21 CFR 208.24, a Medication Guide will be dispensed with each
`OxyContin® prescription. Purdue Pharma L.P. will ensure that the Medication Guide
`is available for distribution to patients receiving a prescription for OxyContin® by
`providing sufficient numbers to distributors and authorized dispensers.
`
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`
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`1. One copy of Full Prescribing Information, which includes the Medication
`Guide, will be packaged with each bottle of OxyContin®.
`
`2. Two separate additional Medication Guides will also be packaged with each
`bottle of OxyContin®.
`
`
`3. Per 21CFR 208.24(d) the label of each container or package of OxyContin®
`will include a prominent and conspicuous statement:
`
`a) instructing authorized dispensers to provide a Medication Guide to each
`patient to whom the drug is dispensed (eg, “Attention Dispenser:
`Accompanying Medication Guide must be provided to each patient upon
`dispensing”), and
`b) stating how the Medication Guide is provided.
`
`
`
`4. Medication Guides will also be available via Purdue Pharma L.P. Field Sales
`representatives, through an Internet presence, and from Purdue’s Medical
`Services Department (1-888-726-7535).
`3.2.3. Elements to Assure Safe Use
`1. Healthcare providers who prescribe OxyContin® will receive training.
`
`a. Purdue will ensure that training will be provided to healthcare providers who
`prescribe OxyContin®. To become trained, each prescriber will be provided with
`the OxyContin® Educational materials.
`
`The Training includes the following:
`
`i) Proper patient selection;
`
`ii) Appropriate OxyContin® dosing and administration;
`
`iii) General principles of safe opioid use, including information about opioid
`abuse and how to identify patients who are at risk for addiction;
`
`iv) Potential abuse, misuse, overdose and addiction from exposure to opioids,
`including OxyContin®;
`
`v) Risks of OxyContin®, including:
`
`1. The risk of overdose caused by exposure to an essentially immediate-
`release form of oxycodone by consuming broken, chewed, crushed or
`dissolved OxyContin® tablets;
`
`2. The risk of addiction from exposure to OxyContin®; and
`
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`3. The risk of overdose in patients who have not developed tolerance to the
`sedating or respiratory-depressant effects of opioids from exposure to a
`single dose of OxyContin greater than 40 mg;
`
`vi) Information to counsel patients and caregivers on the need to store opioid
`analgesics safely out of reach of children and household acquaintances and the
`need to properly dispose of unused drugs when no longer needed by the
`patient; and
`
`vii) Importance of providing each patient a Medication Guide with each
`prescription and instructing the patient to read the Medication Guide.
`
`
`
`b. Purdue will ensure that at least 3 weeks prior to first availability of OxyContin® to
`healthcare professionals, a Dear Healthcare Professional letter will be mailed to
`prescribers most experienced in treating chronic pain with opioid agonists,
`including pain specialists, physiatrists, and primary care physicians. This letter is
`designed to convey and reinforce the risks of abuse, misuse, overdose and
`addiction of OxyContin® as well as the need to complete the OxyContin® REMS
`Educational Program. This letter will be available on the Purdue website
`(www.OxyContinrems.com) for 1 year from the date of mailing.
`
`c. The mailings will include the following OxyContin® REMS Educational Program
`materials:
`
`i) OxyContin® Medication Guide
`
`ii) Prescribing OxyContin® Tablets CII: A Guide for Healthcare Providers
`
`iii) OxyContin® Education Confirmation Form
`
`d. Additional printed educational material will be available through field-force
`distribution and by calling the toll-free number at Purdue (1-888-726-7535).
`
`
`e. The educational material will also be available for download at
`www.OxyContinrems.com.
`
`f. Purdue will maintain a list of all prescribers who have completed the OxyContin®
`REMS Educational Program.
`
`Prescribers will be re-trained every two years or following substantial changes to the
`OxyContin® REMS. Substantial changes may include changes in the OxyContin®
`
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`
`Full Prescribing Information, OxyContin® Medication Guide, or OxyContin® REMS
`that require substantial modification of the educational materials.
`
`The following materials are part of the REMS and are appended:
`o Dear Healthcare Professional Letter
`o Medication Guide
`o The Healthcare Provider Guide, “Prescribing OxyContin® Tablets CII: A
`Training Guide for Healthcare Providers”
`o OxyContin® Education Confirmation Form
`
`Reviewer comment:
`The Sponsor requested that the mailing date of the DHCP letter be closer to the date of
`first shipment [i.e., approximately three weeks prior to first shipment], rather than “within
`60 days of approval” as was specified in the March 18, 2010 Discipline Review (DR)
`letter. DRISK consulted the Office of Compliance (OC) and they agreed to the alternate
`timeframe closer to launch but requested that the date of shipment of the DHCP
`letter/Educational materials and the number of mailings be included in the information
`needed for assessments.
`
`3.2.4 Implementation System
`Because OxyContin® can be approved without the Elements to Assure Safe Use
`described under FDCA 505-1(f)(3) (B), (C), and (D) of the Act, an implementation
`system is not required.
`
`3.2.5. Timetable for Submission of Assessments
`
`Purdue Pharma L.P. will submit REMS Assessments to FDA every 6 months for the first
`year from the date of approval of the REMS and annually thereafter. To facilitate
`inclusion of as much information as possible, while allowing reasonable time to prepare
`the submission, the reporting interval covered by each assessment will conclude no
`earlier than 60 days before the submission date for that assessment. Purdue L.P. will
`submit each assessment so that it will be received by the FDA on or before the due date.
`The REMS Assessment Plan was summarized in the REMS Supporting Document and
`will be included in the approval letter. As part of the negotiations of the final OxyContin
`REMS, comments came from Office of Compliance regarding the information needed for
`Assessments and requested to include the date of the shipment of the DHCL letter and the
`number of mailings. The information needed for assessment will include at a minimum:
`
`
`1. An evaluation of patients’ understanding of the serious risks of OxyContin®.
`
`2. A report on periodic assessments of the distribution and dispensing of the
`Medication Guide in accordance with 21 CFR 208.24.
`
`
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`3. A report on failures to adhere to distribution and dispensing requirements, and
`corrective actions taken to address noncompliance.
`
`4. A report on the status of the training program for healthcare providers
`including the number of Dear Healthcare Professional letters mailed to each
`specialty identified in the REMS, when the letters were mailed, and what
`information was included in the mailings.
`
`
`5. An evaluation of healthcare providers’ awareness and understanding of the
`serious risks associated with OxyContin® (for example, through surveys of
`healthcare providers).
`
`
`6. Specification of measures that would be taken to increase awareness if
`surveys of healthcare providers indicate that healthcare provider awareness is
`not adequate.
`
`7. An analysis and summary of surveillance and monitoring activities for abuse,
`misuse, overdose, and addiction and any intervention taken resulting from
`signals of abuse, misuse, overdose, and addiction.
`
`
`8. A claims study to evaluate OxyContin® (oxycodone hydrochloride) utilization
`patterns including opioid-tolerant utilization patterns before and after
`implementation of the REMS.
`
`
`
`
`
`
`
`9. With respect to REMS goals, an assessment of the extent to which the
` elements to assure safe use are meeting the goals or whether the goals or such
` elements should be modified.
`
`Reviewer comments:
`The Sponsor did not submit the survey instruments or methodologies. Without the
`survey instruments and methodologies there is insufficient information to complete a
`review of the patient and prescriber surveys. The Sponsor was informed on March 18,
`2010 in a DR letter to submit for review the detailed plans that will be used to evaluate
`patients’, prescribers’, and pharmacists’ understanding about the risks associated with
`and safe use of OxyContin® at least 90 days before the evaluation will be conducted. The
`submission should include all methodology and instruments that will be used to evaluate
`the knowledge about the risks associated with and safe use of OxyContin®.
`
`Upon further review it was determined that a pharmacist survey is not necessary as the
`target audience for the mailing and educational materials includes only prescribers.
`Please convey to the Sponsor that a pharmacist survey will not be necessary and refer
`them to the revised comments on the survey methodology (Appendix A).
`
` 4
`
` DISCUSSION AND CONCLUSION
`An interim REMS will be implemented by the Sponsor until a class-wide opioid REMS
`has been approved. The proposed REMS dated March 24, 2010 contains the required
`
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`REMS elements which includes a Medication Guide, element to assure safe use, and a
`timetable for submission of assessments.
`
`The REMS Supporting Document outlines the information that the Sponsor will use to
`assess the effectiveness of the REMS in meeting the goals. The Sponsor did not submit
`the patient and prescriber survey instruments or methodologies; however, this
`information does not need to be submitted for FDA review prior to approval of the
`REMS. The DR letter of March 18, 2010 indicated that the Sponsor must submit for
`review the detailed plans that will be used to evaluate patients’, prescribers’, and
`pharmacists’ understanding about the risks associated with and safe use of OxyContin® at
`least 90 days before the evaluation will be conducted. Please convey to the Sponsor that a
`pharmacist survey will not be necessary and to refer them to the revised comments on the
`surveys (Appendix 1). Please consult DRISK request once the survey instruments and
`methodologies have been submitted by the Sponsor.
`
`Based on our current understanding of the risks of OxyContin®, DRISK believes that a
`REMS comprised of these components is appropriate until a class-wide opioid REMS is
`established.
`
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`
`
`Appendix A: Revised Comments on Survey Methodology and Instruments
`
`
`Submit for review the detailed plan that will be used to evaluate patients’ and
`prescribers’ understanding about the safe use of OxyContin®. The proposed plan
`does not need to be submitted for FDA review prior to approval of the REMS,
`however it should be submitted at least 90 days before the evaluation will be
`conducted. The submission should be coded “REMS Correspondence.” The
`submission should include all methodology and instruments that will be used to
`evaluate the knowledge about the risks associated with and safe use of OxyContin®.
`1. We encourage you to recruit respondents using a multi-modal approach. For
`example, respondents could be recruited online, through physicians’ offices,
`through pharmacies, managed care providers, or through consumer panels.
`Explain how often non-respondent follow-up or reminders will be completed, and
`the planned frequency.
`Explain how an incentive or honorarium will be offered, and the intended amount.
`Explain how any recruitment sites will be selected.
`Submit for review any recruitment advertisements.
`2. Define the sample size and confidence associated with that sample size.
`3. Define the expected number of people to be surveyed, and how the sample will be
`determined (selection criteria).
`4. Explain the inclusion criteria for patients and prescribers; that is, who is an
`eligible respondent. For example, patient respondents might be:
`• Age 18 or older
`• Currently taking OxyContin® or have taken in past 3 months
`• Not currently participating in a clinical trial involving OxyContin®
`• Not a healthcare provider
`Submit any screener instruments, and describe if any quotas of sub-populations
`will be used.
`5. Explain how often surveys will be administered, and the intended frequency.
`Offer respondents multiple options for completing the survey. This is especially
`important for inclusion of the lower literacy population. For example, surveys
`could be completed online or through email, in writing or by mail, over the phone,
`and in person.
`Explain how surveyors will be trained.
`6. Explain controls used to compensate for the limitations or bias associated with the
`methodology.
`7. The sample should be demographically representative of the population who use
`the drug (patients), or prescribe the drug (doctors).
`
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`8. If possible and appropriate, sample should be diverse in terms of: age, race,
`ethnicity, sex, socio-economic status, education level, geographically.
`9. Submit for review the introductory text that will be used to inform respondents
`about the purpose of the survey.
`Potential respondents should be told that their answers will not affect their ability
`to receive or take (patients), prescribe (doctors), and that their answers and
`personal information will be kept confidential and anonymous.
`10. Respondents should not be eligible for more than one wave of the survey.
`11. Results should be analyzed on an item-by-item or variable-by-variable basis. The
`data may be presented using descriptive statistics, such as sample size, mean,
`standard deviation, median, minimum and maximum (for continuous variables),
`and frequency distributions (for categorical variables).
`Data may be stratified by any relevant demographic variable, and presented in
`aggregate. Submit with your assessments all methodology and instruments that
`were utilized.
`Regarding an assessment of patients’ knowledge:
`12. The assessment is to evaluate the effectiveness of the REMS in achieving the goal
`by evaluating patients’ knowledge of the serious risks associated with use of the
`drug; the assessment is not to evaluate consumer comprehension of the
`Medication Guide.
`Other than when the patient received the Medication Guide at the time the
`prescription was filled/dispensed, respondents should not be offered an
`opportunity to read or see the Medication Guide, Package Insert, or any other
`related educational materials again prior to taking the survey.
`13. Submit for review the survey instruments (questionnaires and/or moderator’s
`guide), including any background information on testing survey questions and
`correlation to the messages in the Medication Guide.
`14. The patient knowledge survey should include a section with questions asking
`about the specific risks or safety information conveyed in the Medication Guide to
`see if the patient not only understands the information, but knows what to do if
`they experience the event.
`Most of the risk-specific questions should be derived from information located in
`the “What is the Most Important Information I should know about OxyContin®?”
`section of the Medication Guide.
`The risk-specific questions should be non-biased, non-leading, multiple choice
`questions with the instruction to “select all that apply.” Each question should
`have an “I don’t know” answer option.
`The order of the multiple choice responses should be randomized on each survey.
`15. The order of the patient questions should be such that the risk-specific questions
`are asked first, followed by questions about receipt of the Medication Guide.
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`Demographic questions should be collected last or as part of any screener
`questions.
`Respondents should not have the opportunity or ability to go back to previous
`questions in the survey.
`Explain if and when any education will be offered for incorrect responses.
`16. Include questions about receipt of the Medication Guide in the patient survey as a
`way to fulfill the obligation to report on the distribution of the Medication Guide.
`17. Just prior to the questions about receipt of the Medication Guide, include text that
`describes a Medication Guide. For example,
`Now we are going to ask you some questions about the Medication Guide you
`may have received with OxyContin®. The Medication Guide is a paper handout
`that contains important information about the risks associated with use of
`OxyContin® and how to use OxyContin® safely. Medication Guides always
`include the title “Medication Guide”.
`18. Use the following (or similar) questions to assess receipt and use of the
`Medication Guide.
`• Who gave you the Medication Guide for OxyContin®? (Select all that apply)
`• My doctor or someone in my doctor’s office
`• My pharmacist or someone at the pharmacy
`• Someone else - please explain: ___________________________
`I did not get a Medication Guide for OxyContin®
`•
`• Did you read the Medication Guide?
`• All,
`• Most,
`• Some,
`• None
`• Did you understand what you read in the Medication Guide?
`• All,
`• Most,
`• Some,
`• None
`• Did someone offer to explain to you the information in the Medication Guide?
`• Yes, my doctor or someone in my doctor’s office
`• Yes, my pharmacist or someone at the pharmacy
`• Yes, someone else – please explain:
`______________________________
`• No
`• Did you accept the offer? Yes or No
`• Did you understand the explanation that was given to you?
`• All,
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`• Most,
`• Some,
`• None
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`• Did or do you have any questions about the Medication Guide? Yes or No (If
`Yes, list your question(s) below) Note: This is an open text field that should
`be grouped/coded by the sponsor prior to submitting to FDA
`Regarding an assessment of healthcare providers’ (prescribers) knowledge:
`19. The assessment is to evaluate the effectiveness of the REMS in achieving the goal
`by evaluating healthcare providers’ knowledge of: the serious risks associated
`with use of OxyContin®, how to properly prescribe OxyContin®, and how to how
`to properly monitor for the serious risks associated with the use of OxyContin®;
`th