Association of a Risk Evaluation and Mitigation Strategy Program With Transmucosal Fentanyl Prescribing

William Fleischman, Doris Auth, Nilay D Shah, Shantanu Agrawal, Joseph S. Ross

Research output: Contribution to journalArticle

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Abstract

Importance: Transmucosal immediate-release fentanyl (TIRF) drugs are potent, rapid-acting opioids approved to treat breakthrough pain in patients with cancer who are tolerant to other around-the-clock opioid analgesics. In March 2012, a US Food and Drug Administration-approved Risk Evaluation and Mitigation Strategy (REMS) was implemented, mandating prescribers, distributors, pharmacies, and patients to enroll in the REMS to prescribe, dispense, or receive TIRF drugs. Objective: To evaluate the association of the TIRF-REMS Access Program with TIRF prescribing. Design, Setting, and Participants: Cohort study using an interrupted time series analysis of TIRF prescriptions to Medicare Part D beneficiaries nationwide from 2010 to 2014. Data were analyzed from August 2017 through July 2018. Main Outcomes and Measures: Prescribing of TIRF per 100 000 Medicare Part D beneficiaries, overall and stratified by cancer status; percentage of TIRF prescriptions for patients without cancer, overall and by brand; and percentage of TIRF prescriptions for patients without known opioid tolerance, defined as patients prescribed at least 60 morphine milligram equivalents per day, overall and by brand. Results: There were 99 601 TIRF prescriptions written by 8619 clinicians to 10 472 patients. Most of the patients (79%) were younger than 65 years (mean [SD] age, 56 [13] years), and most (67%) did not have cancer. Implementation of TIRF-REMS was associated with a 26.7% relative level decrease in TIRF prescribing (95% CI, -33.3% to -19.4%; P < .001) but was followed by 2.0% monthly increases in prescribing (95% CI, 1.3% to 2.7%; P < .001). Sensitivity analyses that accounted for overall opioid prescribing trends were consistent with these findings. Furthermore, there were no significant changes associated with REMS implementation in the level (0.47%; 95% CI, -5.36% to 4.69%; P = .85) or trend (0.16%; 95% CI, -0.06% to 0.37%; P = .15) of the percentage of prescriptions for patients without cancer. However, a sensitivity analysis that used a broader cancer definition found implementation was associated with a 7.2% (95% CI, -13.5% to -0.48%; P = .04) level decrease in the percentage of TIRF prescriptions for patients without cancer. Lastly, the TIRF-REMS was associated with a 22.5% level decline in the percentage of TIRF prescriptions for patients without known opioid tolerance (95% CI, -36.1% to -5.95%; P = .01) followed by 1.98% monthly decreases (95% CI, -3.19% to -0.80%; P = .001). Conclusions and Relevance: Implementation of the TIRF-REMS Access Program, a restrictive drug distribution program, was associated with a temporary reduction in the rate of TIRF prescribing to Medicare Part D beneficiaries, and with a sustained decrease in the percentage of TIRF prescriptions for patients without known opioid tolerance. Implementation may have also been associated with a temporary decrease in the percentage of TIRF prescriptions for patients without cancer.

Original languageEnglish (US)
Pages (from-to)e191340
JournalJAMA network open
Volume2
Issue number3
DOIs
StatePublished - Mar 1 2019

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Fentanyl
Prescriptions
Opioid Analgesics
Medicare Part D
Neoplasms
Breakthrough Pain
Pharmacies
United States Food and Drug Administration

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Association of a Risk Evaluation and Mitigation Strategy Program With Transmucosal Fentanyl Prescribing. / Fleischman, William; Auth, Doris; Shah, Nilay D; Agrawal, Shantanu; Ross, Joseph S.

In: JAMA network open, Vol. 2, No. 3, 01.03.2019, p. e191340.

Research output: Contribution to journalArticle

Fleischman, William ; Auth, Doris ; Shah, Nilay D ; Agrawal, Shantanu ; Ross, Joseph S. / Association of a Risk Evaluation and Mitigation Strategy Program With Transmucosal Fentanyl Prescribing. In: JAMA network open. 2019 ; Vol. 2, No. 3. pp. e191340.
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title = "Association of a Risk Evaluation and Mitigation Strategy Program With Transmucosal Fentanyl Prescribing",
abstract = "Importance: Transmucosal immediate-release fentanyl (TIRF) drugs are potent, rapid-acting opioids approved to treat breakthrough pain in patients with cancer who are tolerant to other around-the-clock opioid analgesics. In March 2012, a US Food and Drug Administration-approved Risk Evaluation and Mitigation Strategy (REMS) was implemented, mandating prescribers, distributors, pharmacies, and patients to enroll in the REMS to prescribe, dispense, or receive TIRF drugs. Objective: To evaluate the association of the TIRF-REMS Access Program with TIRF prescribing. Design, Setting, and Participants: Cohort study using an interrupted time series analysis of TIRF prescriptions to Medicare Part D beneficiaries nationwide from 2010 to 2014. Data were analyzed from August 2017 through July 2018. Main Outcomes and Measures: Prescribing of TIRF per 100 000 Medicare Part D beneficiaries, overall and stratified by cancer status; percentage of TIRF prescriptions for patients without cancer, overall and by brand; and percentage of TIRF prescriptions for patients without known opioid tolerance, defined as patients prescribed at least 60 morphine milligram equivalents per day, overall and by brand. Results: There were 99 601 TIRF prescriptions written by 8619 clinicians to 10 472 patients. Most of the patients (79{\%}) were younger than 65 years (mean [SD] age, 56 [13] years), and most (67{\%}) did not have cancer. Implementation of TIRF-REMS was associated with a 26.7{\%} relative level decrease in TIRF prescribing (95{\%} CI, -33.3{\%} to -19.4{\%}; P < .001) but was followed by 2.0{\%} monthly increases in prescribing (95{\%} CI, 1.3{\%} to 2.7{\%}; P < .001). Sensitivity analyses that accounted for overall opioid prescribing trends were consistent with these findings. Furthermore, there were no significant changes associated with REMS implementation in the level (0.47{\%}; 95{\%} CI, -5.36{\%} to 4.69{\%}; P = .85) or trend (0.16{\%}; 95{\%} CI, -0.06{\%} to 0.37{\%}; P = .15) of the percentage of prescriptions for patients without cancer. However, a sensitivity analysis that used a broader cancer definition found implementation was associated with a 7.2{\%} (95{\%} CI, -13.5{\%} to -0.48{\%}; P = .04) level decrease in the percentage of TIRF prescriptions for patients without cancer. Lastly, the TIRF-REMS was associated with a 22.5{\%} level decline in the percentage of TIRF prescriptions for patients without known opioid tolerance (95{\%} CI, -36.1{\%} to -5.95{\%}; P = .01) followed by 1.98{\%} monthly decreases (95{\%} CI, -3.19{\%} to -0.80{\%}; P = .001). Conclusions and Relevance: Implementation of the TIRF-REMS Access Program, a restrictive drug distribution program, was associated with a temporary reduction in the rate of TIRF prescribing to Medicare Part D beneficiaries, and with a sustained decrease in the percentage of TIRF prescriptions for patients without known opioid tolerance. Implementation may have also been associated with a temporary decrease in the percentage of TIRF prescriptions for patients without cancer.",
author = "William Fleischman and Doris Auth and Shah, {Nilay D} and Shantanu Agrawal and Ross, {Joseph S.}",
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T1 - Association of a Risk Evaluation and Mitigation Strategy Program With Transmucosal Fentanyl Prescribing

AU - Fleischman, William

AU - Auth, Doris

AU - Shah, Nilay D

AU - Agrawal, Shantanu

AU - Ross, Joseph S.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Importance: Transmucosal immediate-release fentanyl (TIRF) drugs are potent, rapid-acting opioids approved to treat breakthrough pain in patients with cancer who are tolerant to other around-the-clock opioid analgesics. In March 2012, a US Food and Drug Administration-approved Risk Evaluation and Mitigation Strategy (REMS) was implemented, mandating prescribers, distributors, pharmacies, and patients to enroll in the REMS to prescribe, dispense, or receive TIRF drugs. Objective: To evaluate the association of the TIRF-REMS Access Program with TIRF prescribing. Design, Setting, and Participants: Cohort study using an interrupted time series analysis of TIRF prescriptions to Medicare Part D beneficiaries nationwide from 2010 to 2014. Data were analyzed from August 2017 through July 2018. Main Outcomes and Measures: Prescribing of TIRF per 100 000 Medicare Part D beneficiaries, overall and stratified by cancer status; percentage of TIRF prescriptions for patients without cancer, overall and by brand; and percentage of TIRF prescriptions for patients without known opioid tolerance, defined as patients prescribed at least 60 morphine milligram equivalents per day, overall and by brand. Results: There were 99 601 TIRF prescriptions written by 8619 clinicians to 10 472 patients. Most of the patients (79%) were younger than 65 years (mean [SD] age, 56 [13] years), and most (67%) did not have cancer. Implementation of TIRF-REMS was associated with a 26.7% relative level decrease in TIRF prescribing (95% CI, -33.3% to -19.4%; P < .001) but was followed by 2.0% monthly increases in prescribing (95% CI, 1.3% to 2.7%; P < .001). Sensitivity analyses that accounted for overall opioid prescribing trends were consistent with these findings. Furthermore, there were no significant changes associated with REMS implementation in the level (0.47%; 95% CI, -5.36% to 4.69%; P = .85) or trend (0.16%; 95% CI, -0.06% to 0.37%; P = .15) of the percentage of prescriptions for patients without cancer. However, a sensitivity analysis that used a broader cancer definition found implementation was associated with a 7.2% (95% CI, -13.5% to -0.48%; P = .04) level decrease in the percentage of TIRF prescriptions for patients without cancer. Lastly, the TIRF-REMS was associated with a 22.5% level decline in the percentage of TIRF prescriptions for patients without known opioid tolerance (95% CI, -36.1% to -5.95%; P = .01) followed by 1.98% monthly decreases (95% CI, -3.19% to -0.80%; P = .001). Conclusions and Relevance: Implementation of the TIRF-REMS Access Program, a restrictive drug distribution program, was associated with a temporary reduction in the rate of TIRF prescribing to Medicare Part D beneficiaries, and with a sustained decrease in the percentage of TIRF prescriptions for patients without known opioid tolerance. Implementation may have also been associated with a temporary decrease in the percentage of TIRF prescriptions for patients without cancer.

AB - Importance: Transmucosal immediate-release fentanyl (TIRF) drugs are potent, rapid-acting opioids approved to treat breakthrough pain in patients with cancer who are tolerant to other around-the-clock opioid analgesics. In March 2012, a US Food and Drug Administration-approved Risk Evaluation and Mitigation Strategy (REMS) was implemented, mandating prescribers, distributors, pharmacies, and patients to enroll in the REMS to prescribe, dispense, or receive TIRF drugs. Objective: To evaluate the association of the TIRF-REMS Access Program with TIRF prescribing. Design, Setting, and Participants: Cohort study using an interrupted time series analysis of TIRF prescriptions to Medicare Part D beneficiaries nationwide from 2010 to 2014. Data were analyzed from August 2017 through July 2018. Main Outcomes and Measures: Prescribing of TIRF per 100 000 Medicare Part D beneficiaries, overall and stratified by cancer status; percentage of TIRF prescriptions for patients without cancer, overall and by brand; and percentage of TIRF prescriptions for patients without known opioid tolerance, defined as patients prescribed at least 60 morphine milligram equivalents per day, overall and by brand. Results: There were 99 601 TIRF prescriptions written by 8619 clinicians to 10 472 patients. Most of the patients (79%) were younger than 65 years (mean [SD] age, 56 [13] years), and most (67%) did not have cancer. Implementation of TIRF-REMS was associated with a 26.7% relative level decrease in TIRF prescribing (95% CI, -33.3% to -19.4%; P < .001) but was followed by 2.0% monthly increases in prescribing (95% CI, 1.3% to 2.7%; P < .001). Sensitivity analyses that accounted for overall opioid prescribing trends were consistent with these findings. Furthermore, there were no significant changes associated with REMS implementation in the level (0.47%; 95% CI, -5.36% to 4.69%; P = .85) or trend (0.16%; 95% CI, -0.06% to 0.37%; P = .15) of the percentage of prescriptions for patients without cancer. However, a sensitivity analysis that used a broader cancer definition found implementation was associated with a 7.2% (95% CI, -13.5% to -0.48%; P = .04) level decrease in the percentage of TIRF prescriptions for patients without cancer. Lastly, the TIRF-REMS was associated with a 22.5% level decline in the percentage of TIRF prescriptions for patients without known opioid tolerance (95% CI, -36.1% to -5.95%; P = .01) followed by 1.98% monthly decreases (95% CI, -3.19% to -0.80%; P = .001). Conclusions and Relevance: Implementation of the TIRF-REMS Access Program, a restrictive drug distribution program, was associated with a temporary reduction in the rate of TIRF prescribing to Medicare Part D beneficiaries, and with a sustained decrease in the percentage of TIRF prescriptions for patients without known opioid tolerance. Implementation may have also been associated with a temporary decrease in the percentage of TIRF prescriptions for patients without cancer.

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