DODAC and DSaRM Advisory Committee August 1, 2007 Pregnancy Registry and Root Cause Analysis Cynthia Kornegay, Ph.D. Division of Drug Risk Evaluation Office

DODAC and DSaRM Advisory Committee DODAC and DSaRM Advisory Committee August 1, 2007August 1, 2007

Pregnancy Registry andPregnancy Registry and Root Cause Analysis Root Cause Analysis

Pregnancy Registry andPregnancy Registry and Root Cause Analysis Root Cause Analysis

Cynthia Kornegay, Ph.D.Cynthia Kornegay, Ph.D.

Division of Drug Risk EvaluationDivision of Drug Risk EvaluationOffice of Surveillance and EpidemiologyOffice of Surveillance and Epidemiology

Center for Drug Evaluation and Research Center for Drug Evaluation and Research

Food and Drug AdministrationFood and Drug Administration

Cynthia Kornegay, Ph.D.Cynthia Kornegay, Ph.D.

Division of Drug Risk EvaluationDivision of Drug Risk EvaluationOffice of Surveillance and EpidemiologyOffice of Surveillance and Epidemiology

Center for Drug Evaluation and Research Center for Drug Evaluation and Research

Food and Drug AdministrationFood and Drug Administration

2DODAC and DSaRM Advisory Committee DODAC and DSaRM Advisory Committee August 1, 2007August 1, 2007

OutlineOutlineOutlineOutline

• Challenges– Pregnancy Registry and Root Cause Analysis

• Background• Possible Barriers• Considerations

– Knowledge and Behavior Assessment• Background• Possible Barriers• Considerations

• Comparison Group• Preliminary Observations

• Challenges– Pregnancy Registry and Root Cause Analysis

• Background• Possible Barriers• Considerations

– Knowledge and Behavior Assessment• Background• Possible Barriers• Considerations

• Comparison Group• Preliminary Observations


Pregnancy Registry and Root Pregnancy Registry and Root Cause Analysis (RCA)Cause Analysis (RCA)

Pregnancy Registry and Root Pregnancy Registry and Root Cause Analysis (RCA)Cause Analysis (RCA)


Background – Background – Pregnancy Registry and RCAPregnancy Registry and RCA


• Root Cause Analysis (RCA) proposed by 2004 AC committee– Purpose is to gather detailed information on all

reported isotretinoin-exposed pregnancies and use aggregate data to improve iPLEDGE program

• Root Cause Analysis (RCA) proposed by 2004 AC committee– Purpose is to gather detailed information on all

reported isotretinoin-exposed pregnancies and use aggregate data to improve iPLEDGE program




• All women who become pregnant are asked to participate in the Registry– Initial data collected at time pregnancy

reported with quarterly follow-up until infant is up to 1 year old

• The RCA is administered as part of the Registry

• All women who become pregnant are asked to participate in the Registry– Initial data collected at time pregnancy

reported with quarterly follow-up until infant is up to 1 year old

• The RCA is administered as part of the Registry


Background – Background – Pregnancy Registry and RCA Pregnancy Registry and RCA

Background – Background – Pregnancy Registry and RCA Pregnancy Registry and RCA

• For the first year of iPLEDGE, the RCA participation rate was approximately 10% the total number of eligible pregnancies*– Insufficient enrollment to use data for

improving iPLEDGE

• For the first year of iPLEDGE, the RCA participation rate was approximately 10% the total number of eligible pregnancies*– Insufficient enrollment to use data for

improving iPLEDGE

*Data derived from iPLEDGE Quarterly Reports from January 1, 2006 through March 31, 2007.


Possible Participation Barriers –Possible Participation Barriers –Pregnancy Registry and RCAPregnancy Registry and RCA


• Reasons for low participation are not known, but several possible barriers may exist– Significant time element involved in

participation– Additional informed consent and

lengthy questionnaires– Intrusive nature of RCA

• Reasons for low participation are not known, but several possible barriers may exist– Significant time element involved in

participation– Additional informed consent and

lengthy questionnaires– Intrusive nature of RCA




• Possible barriers (cont.)– iPLEDGE prescriber may not have

further contact with participant– Registry is not widely promoted– RCA is administered only after

introductory reporting forms have been completed

• Possible barriers (cont.)– iPLEDGE prescriber may not have

further contact with participant– Registry is not widely promoted– RCA is administered only after

introductory reporting forms have been completed


Considerations – Considerations – Pregnancy Registry and RCAPregnancy Registry and RCA

Considerations – Considerations – Pregnancy Registry and RCAPregnancy Registry and RCA

• To help increase participation:– Streamline informed consent process

and questionnaires– Continue to ensure interviewers present

questionnaire in non-judgmental manner

– Increase awareness– Collect RCA information as soon as

possible after pregnancy is reported

• To help increase participation:– Streamline informed consent process

and questionnaires– Continue to ensure interviewers present

questionnaire in non-judgmental manner

– Increase awareness– Collect RCA information as soon as

possible after pregnancy is reported


Knowledge and Behavior Knowledge and Behavior AssessmentAssessment

Knowledge and Behavior Knowledge and Behavior AssessmentAssessment


Background – Background – Knowledge and Behavior AssessmentKnowledge and Behavior Assessment


• Patient education is primary method of risk communication in iPLEDGE– Brochures, workbooks, and videos are

available for patients and prescribers– All patients receive basic materials, but

females of childbearing potential also get additional brochures targeted specifically for them

• Patient education is primary method of risk communication in iPLEDGE– Brochures, workbooks, and videos are

available for patients and prescribers– All patients receive basic materials, but

females of childbearing potential also get additional brochures targeted specifically for them




• iPLEDGE makes effort to provide adequate contraceptive counseling– iPLEDGE prescribers are required to

provide contraceptive counseling as part of the program

– Health care providers can refer patients to contraceptive counselors

– Initial contraceptive counseling is provided free of charge if requested

• iPLEDGE makes effort to provide adequate contraceptive counseling– iPLEDGE prescribers are required to

provide contraceptive counseling as part of the program

– Health care providers can refer patients to contraceptive counselors

– Initial contraceptive counseling is provided free of charge if requested




• Females of childbearing potential must answer a series of questions every month of therapy to assess knowledge of iPLEDGE– At start, questions focus on receipt of

iPLEDGE materials– During therapy, questions assess

contraceptive practices – Must be answered prior to receiving each

prescription

• Females of childbearing potential must answer a series of questions every month of therapy to assess knowledge of iPLEDGE– At start, questions focus on receipt of

iPLEDGE materials– During therapy, questions assess

contraceptive practices – Must be answered prior to receiving each

prescription


Possible Barriers – Possible Barriers – Knowledge and Behavior AssessmentKnowledge and Behavior Assessment


• Possible information overload– Females of childbearing potential

receive over 50 pages of materials at the start of therapy

– Research suggests that even when more information is available, patients may still not understand the risks associated with isotretinoin*

• Possible information overload– Females of childbearing potential

receive over 50 pages of materials at the start of therapy

– Research suggests that even when more information is available, patients may still not understand the risks associated with isotretinoin*

*Allen LaPointe et al. Patient receipt and understanding of written information provided with isotretinoin and estrogen prescriptions. J Gen Intern Med 2007 Jan;22(1):98-101




• Inconsistencies regarding initial counseling by females of childbearing potential– Patient informed consent states that

they have received counseling from their iPLEDGE prescriber

– About 13% of patients reported not receiving contraceptive counseling when starting isotretinoin therapy*

• Inconsistencies regarding initial counseling by females of childbearing potential– Patient informed consent states that

they have received counseling from their iPLEDGE prescriber

– About 13% of patients reported not receiving contraceptive counseling when starting isotretinoin therapy*

*iPLEDGE Year 1 Report, Table 7, March 30, 2007




• Possible disconnect between reading and comprehension of program materials– Although response rates indicate that

over 95% of women had read the materials*:

• 38% of women answered the question “ You can use any forms of birth control for iPLEDGE” incorrectly**

• Possible disconnect between reading and comprehension of program materials– Although response rates indicate that

over 95% of women had read the materials*:

• 38% of women answered the question “ You can use any forms of birth control for iPLEDGE” incorrectly**

*iPLEDGE 4th Quarter 2006 Report, Table B.1, January 31, 2007**iPLEDGE 4th Quarter 2006 Report, Table B.1.5, January 31, 2007




• Monthly questions may need to be revised– Depending on the birth control method

chosen, between 21% and 62% of women answered a key birth control question incorrectly*

– Wording has been improved in recent changes proposed by Sponsors

• Monthly questions may need to be revised– Depending on the birth control method

chosen, between 21% and 62% of women answered a key birth control question incorrectly*

– Wording has been improved in recent changes proposed by Sponsors

*iPLEDGE 4th Quarter 2006 Report, Table B.1.5, January 31, 2007


Considerations – Considerations – Knowledge and Behavior AssessmentKnowledge and Behavior Assessment


• Reduce length of materials• Streamline message on essentials of

iPLEDGE• Review materials to ensure clear,

consistent and patient-friendly language

• Changes to materials should be tested prior to distributing as part of iPLEDGE

• Reduce length of materials• Streamline message on essentials of

iPLEDGE• Review materials to ensure clear,

consistent and patient-friendly language

• Changes to materials should be tested prior to distributing as part of iPLEDGE




• Although patients may receive their contraception from other healthcare providers, isotretinoin prescribers still need to review iPLEDGE’s additional contraceptive requirements with females of child-bearing potential– Two forms of birth control must be

emphasized

• Although patients may receive their contraception from other healthcare providers, isotretinoin prescribers still need to review iPLEDGE’s additional contraceptive requirements with females of child-bearing potential– Two forms of birth control must be

emphasized




• Ongoing review of questions should continue to ensure that:– They are focused on demonstrating

knowledge of the iPLEDGE program– They are clearly worded– Correct answers pertain to iPLEDGE– They provide an accurate assessment

of knowledge

• Ongoing review of questions should continue to ensure that:– They are focused on demonstrating

knowledge of the iPLEDGE program– They are clearly worded– Correct answers pertain to iPLEDGE– They provide an accurate assessment

of knowledge


Comparison GroupComparison GroupComparison GroupComparison Group



• RCA gathers retrospective data on actual contraceptive use

• Comparable information is not available for women who did not get pregnant

• This comparison will help place RCA data in context

• RCA gathers retrospective data on actual contraceptive use

• Comparable information is not available for women who did not get pregnant

• This comparison will help place RCA data in context



• The Agency and Sponsors need to – Consider additional studies to provide

data on non-pregnant females’ contraceptive behaviors for comparison

• Random sample of non-pregnant females (age matched)

– Should help make evaluation of iPLEDGE more informative

• The Agency and Sponsors need to – Consider additional studies to provide

data on non-pregnant females’ contraceptive behaviors for comparison

• Random sample of non-pregnant females (age matched)

– Should help make evaluation of iPLEDGE more informative


Preliminary ObservationsPreliminary ObservationsPreliminary ObservationsPreliminary Observations



• Concerns:– RCA participation rate– Patient understanding of risks

associated with isotretinoin– Evaluation of patient knowledge

• Needs to be valid assessment

• Consideration for minor program adjustments might be helpful– Concerns about program disruption

• Concerns:– RCA participation rate– Patient understanding of risks

associated with isotretinoin– Evaluation of patient knowledge

• Needs to be valid assessment

• Consideration for minor program adjustments might be helpful– Concerns about program disruption



• Evaluation goal is to determine if there are areas of iPLEDGE that can be enhanced to improve the program’s overall effectiveness– Behavior change can be difficult to

achieve – iPLEDGE program effectiveness may be

limited by non-program factors (motivation, perception of risk)

• Evaluation goal is to determine if there are areas of iPLEDGE that can be enhanced to improve the program’s overall effectiveness– Behavior change can be difficult to

achieve – iPLEDGE program effectiveness may be

limited by non-program factors (motivation, perception of risk)

Documents

DODAC and DSaRM Advisory Committee August 1, 2007 Pregnancy Registry and Root Cause Analysis Cynthia Kornegay, Ph.D. Division of Drug Risk Evaluation Office