A pragmatic utility function to describe the risk-benefit composite of opioid and non-opioid analgesic medication

Albert Dahan, Anne Olesen, Suzanne Broens, Soren Olesen, Monique van Velzen, Asbjorn Drewes, Marieke Niesters, Erik Olofsen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

It is not straightforward to simultaneously evaluate benefits and harms of pain management, as different drugs may possess different analgesia and adverse effect profiles. Utility functions, derived from the pharmacokinetics and pharmacodynamics of individual outcome parameters, have been constructed to address this problem. Here we construct "pragmatic" utility functions based on measurements of benefit and harms, but without making assumptions about the underlying pharmacokinetics and pharmacodynamics. Using data from two previous studies, utility functions were designed by estimating the probability of occurrence of benefit and harm and combining these into one function. Study 1 was a clinical trial on the effect of oral pregabalin on pain relief in chronic pancreatitis patients, with end-points analgesia and dizziness monitored for 21 days. Study 2 was an experimental study on the effect of intravenous fentanyl on antinociception and respiratory depression in healthy volunteers. From study 1 the utility function was negative the first week of treatment, indicative of the greater probability of dizziness than analgesia, but positive thereafter. From study 2 the utility function showed a nadir 30 minutes after dosing, after which the probability function slowly increased towards zero. A pragmatic utility function based on the probability of two binary outcomes, analgesia and adverse effect, was successfully constructed using data from two previous studies. Results yielded valuable insights into the utility of treatment and may be highly educative for physicians and may be used in development of potent analgesics with serious side effects.

OriginalsprogEngelsk
TidsskriftThe Journal of Pharmacology and Experimental Therapeutics
ISSN0022-3565
DOI
StatusE-pub ahead of print - 15 nov. 2018

Fingeraftryk

Analgesia
Opioid Analgesics
Analgesics
Dizziness
Pharmacokinetics
Chronic Pancreatitis
Fentanyl
Pain Management
Respiratory Insufficiency
Healthy Volunteers
Clinical Trials
Physicians
Pain
Therapeutics
Pharmaceutical Preparations

Citer dette

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abstract = "It is not straightforward to simultaneously evaluate benefits and harms of pain management, as different drugs may possess different analgesia and adverse effect profiles. Utility functions, derived from the pharmacokinetics and pharmacodynamics of individual outcome parameters, have been constructed to address this problem. Here we construct {"}pragmatic{"} utility functions based on measurements of benefit and harms, but without making assumptions about the underlying pharmacokinetics and pharmacodynamics. Using data from two previous studies, utility functions were designed by estimating the probability of occurrence of benefit and harm and combining these into one function. Study 1 was a clinical trial on the effect of oral pregabalin on pain relief in chronic pancreatitis patients, with end-points analgesia and dizziness monitored for 21 days. Study 2 was an experimental study on the effect of intravenous fentanyl on antinociception and respiratory depression in healthy volunteers. From study 1 the utility function was negative the first week of treatment, indicative of the greater probability of dizziness than analgesia, but positive thereafter. From study 2 the utility function showed a nadir 30 minutes after dosing, after which the probability function slowly increased towards zero. A pragmatic utility function based on the probability of two binary outcomes, analgesia and adverse effect, was successfully constructed using data from two previous studies. Results yielded valuable insights into the utility of treatment and may be highly educative for physicians and may be used in development of potent analgesics with serious side effects.",
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A pragmatic utility function to describe the risk-benefit composite of opioid and non-opioid analgesic medication. / Dahan, Albert; Olesen, Anne; Broens, Suzanne; Olesen, Soren; van Velzen, Monique; Drewes, Asbjorn; Niesters, Marieke; Olofsen, Erik.

I: The Journal of Pharmacology and Experimental Therapeutics, 15.11.2018.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - A pragmatic utility function to describe the risk-benefit composite of opioid and non-opioid analgesic medication

AU - Dahan, Albert

AU - Olesen, Anne

AU - Broens, Suzanne

AU - Olesen, Soren

AU - van Velzen, Monique

AU - Drewes, Asbjorn

AU - Niesters, Marieke

AU - Olofsen, Erik

PY - 2018/11/15

Y1 - 2018/11/15

N2 - It is not straightforward to simultaneously evaluate benefits and harms of pain management, as different drugs may possess different analgesia and adverse effect profiles. Utility functions, derived from the pharmacokinetics and pharmacodynamics of individual outcome parameters, have been constructed to address this problem. Here we construct "pragmatic" utility functions based on measurements of benefit and harms, but without making assumptions about the underlying pharmacokinetics and pharmacodynamics. Using data from two previous studies, utility functions were designed by estimating the probability of occurrence of benefit and harm and combining these into one function. Study 1 was a clinical trial on the effect of oral pregabalin on pain relief in chronic pancreatitis patients, with end-points analgesia and dizziness monitored for 21 days. Study 2 was an experimental study on the effect of intravenous fentanyl on antinociception and respiratory depression in healthy volunteers. From study 1 the utility function was negative the first week of treatment, indicative of the greater probability of dizziness than analgesia, but positive thereafter. From study 2 the utility function showed a nadir 30 minutes after dosing, after which the probability function slowly increased towards zero. A pragmatic utility function based on the probability of two binary outcomes, analgesia and adverse effect, was successfully constructed using data from two previous studies. Results yielded valuable insights into the utility of treatment and may be highly educative for physicians and may be used in development of potent analgesics with serious side effects.

AB - It is not straightforward to simultaneously evaluate benefits and harms of pain management, as different drugs may possess different analgesia and adverse effect profiles. Utility functions, derived from the pharmacokinetics and pharmacodynamics of individual outcome parameters, have been constructed to address this problem. Here we construct "pragmatic" utility functions based on measurements of benefit and harms, but without making assumptions about the underlying pharmacokinetics and pharmacodynamics. Using data from two previous studies, utility functions were designed by estimating the probability of occurrence of benefit and harm and combining these into one function. Study 1 was a clinical trial on the effect of oral pregabalin on pain relief in chronic pancreatitis patients, with end-points analgesia and dizziness monitored for 21 days. Study 2 was an experimental study on the effect of intravenous fentanyl on antinociception and respiratory depression in healthy volunteers. From study 1 the utility function was negative the first week of treatment, indicative of the greater probability of dizziness than analgesia, but positive thereafter. From study 2 the utility function showed a nadir 30 minutes after dosing, after which the probability function slowly increased towards zero. A pragmatic utility function based on the probability of two binary outcomes, analgesia and adverse effect, was successfully constructed using data from two previous studies. Results yielded valuable insights into the utility of treatment and may be highly educative for physicians and may be used in development of potent analgesics with serious side effects.

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JO - The Journal of Pharmacology and Experimental Therapeutics

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