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General medicine
Systematic benefit-risk assessment for buprenorphine implant: a semiquantitative method to support risk management
  1. Vicki Osborne1,2,
  2. Miranda Davies1,2,
  3. Debabrata Roy1,2,
  4. Francesco Tescione3,
  5. Saad A W Shakir1,2
  1. 1Drug Safety Research Unit, Southampton, UK
  2. 2School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK
  3. 3L Molteni & C dei F.lli Alitti, Scandicci, Italy
  1. Correspondence to Dr Vicki Osborne, Drug Safety Research Unit, Southampton SO31 1AA, UK; vicki.osborne{at}


Background Prior to approval in the European Union, a systematic benefit-risk assessment was required to compare buprenorphine implant to sublingual buprenorphine as part of the license application to the European Medicines Agency.

Objective The Benefit-Risk Action Team framework was used to describe the overall benefit-risk of buprenorphine implant in comparison to sublingual buprenorphine.

Study selection/methods A value tree of key benefits and risks related to the implant formulation of buprenorphine was constructed. Risk differences (RD) or reporting ORs (ROR) and corresponding 95% CIs were calculated for each outcome, along with the number needed to treat and number needed to harm. Swing weighting was assigned to outcomes and the weighted net clinical benefit (wNCB) was calculated.

Findings Key benefits assessed: reduced risk of illicit opioid use (RD=0.09, 95% CI 0.01 to 0.17), reduced risk of misuse and diversion (ROR=0.13, 95% CI 0.02 to 0.94), improved compliance and convenience (RD=0.20) and quality of life measures (RD=0.03). Key risks assessed: clinically significant implant breakage (RD=0.01, 95% CI 0.00 to 0.01), migration/missing implant (RD=0.01, 95% CI 0.00 to 0.02), infection at insertion/removal site (RD=0.08, 95% CI 0.03 to 0.12) and implant-related allergic reaction (RD=0.07, 95% CI 0.03 to 0.11). The wNCB for buprenorphine implant was 4.96, which suggests a favourable benefit-risk profile.

Conclusions The benefit-risk profile of buprenorphine implant is considered favourable in comparison to sublingual buprenorphine, based on this semiquantitative analysis using available data. Further data from real-world use on benefits and risks should be used for ongoing monitoring of the benefit-risk profile of buprenorphine implants in the postmarketing setting.

  • substance misuse
  • public health

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  • Contributors VO, MD, DR and SAWS designed the study and consulted with FT regarding the design. VO, MD and DR conducted the study and interpreted the data. The manuscript was written primarily by VO. All authors reviewed, contributed to revisions and approved the manuscript, and accept full responsibility for its overall content.

  • Funding The Drug Safety Research Unit (DSRU) is an independent academic institution which works in association with the University of Portsmouth. The DSRU has received funding from L Molteni & C dei F.lli Alitti, the marketing authorisation holder for Sixmo, to conduct this study. The funding source was consulted during the study design phase but the final decision on study design was made by the DSRU.

  • Disclaimer The funding source had no role in the collection, analysis and interpretation of data, though was consulted at the time of writing the report and the manuscript. The final decision on content and to submit the article for publication was made by the DSRU.

  • Competing interests FT is an employee of L Molteni & C dei F.lli Alitti, the marketing authorisation holder for Sixmo. VO, MD, DR and SAWS have no competing interests to declare.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data sharing is not applicable as no data sets were generated and/or analysed for this study. Data used in this analysis are available from the references supplied.

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