Buprenorphine Butrans — Buprenorphine is an FDA-approved medication for the treatment of opioid use disorder. It is about 25 to times more potent than morphine, but it does not provide a euphoric high like other opioids. Buprenorphine is used in drug detox to relieve and reduce opioid withdrawal symptoms.
Oxymorphone — Oxymorphone is sold under brand names such as Opana and Numorphone. Oxymorphone is used to relieve moderate to severe pain in patients who are unable to reduce or control pain with other medications. Oxymorphone is 3 times stronger than morphine when taken in tablet form, and 10 times stronger than morphine when received as an intravenous injection.
Hydromorphone — Hydromorphone is used to relieve moderate to severe pain and is about two to eight times more potent than morphine, reports the DEA. It is available as an injection, tablet, liquid, and rectal suppository. Heroin — Heroin is an illicit drug classified as a Schedule I substance with a high potential for abuse.
Heroin is usually two to five times stronger than morphine and commonly mixed with other potent substances such as fentanyl or carfentanil. In , heroin was involved in 14, overdose deaths in the U. Methadone Dolophine, Methadose — Methadone is another FDA-approved medication for the treatment of opioid addiction and is about three times stronger than morphine.
Methadone is often used for long-term maintenance in people in recovery from opioid addiction, and can only be dispensed at an outpatient clinic under direct medical supervision. OxyContin — OxyContin is a brand name for Oxycodone, a well-known extended-release opioid. The CDC reports that oxycodone is one of the most common drugs involved in prescription opioid overdose deaths. In , prescription opioids like oxycodone contributed to 14, overdose deaths in the U.
It is usually sold as a tablet that is meant to last an entire day, which is often bypassed by drug abusers to quicken the release time. Street names include O. Percocet — This drug is a combination of oxycodone and acetaminophen. We contacted authors of all the included studies to acquire details as possible.
Publication bias was assessed through testing funnel plot asymmetry which should be interpreted in the light of visual inspection of the funnel plot [ 18 ]. Two types of costs were included in the model: costs associated with cancer pain titration and adverse drug reactions. Costs of cancer pain titration consisted of CR oxycodone, SR morphine and morphine hydrochloride tablets. The probabilities of occurrence of adverse drug reactions were derived from our included studies. The costs of adverse drug reactions were calculated as incidence of adverse drug reactions multiplied by costs of medicine for corresponding events.
The resource utilization was estimated based on patient records reviewed at the Sichuan cancer hospital. We adopted phenolphthalein, metoclopramide, diphenhydramine, megestrol and catheterization to manage constipation, emesis, pruritus, anorexia and urinary retentron respectively.
The total costs of cancer pain titration and adverse drug reactions were estimated based on official pricelist of National Health Commission of P. Detailed information of unit costs were shown in Table 1. The costs of cancer pain titration and adverse drug reactions were shown in Table 2.
The decision-tree-based incremental cost-effectiveness analysis was performed with Decision Tree Software TreeAge Pro The events examined in the decision tree were pain controlled rate while receiving opioid titration within model cycle. The probabilities used in the decision tree were determined from the meta-analysis of efficacy and safety.
The costs used in the decision tree were those determined in our analysis of the costs of treatment and adverse drug reactions. In the absence of specific utility value for cancer pain titration, we used pain control rate to estimate efficacy.
According to NRS score: 0 refers painless; 1—3 refers to mild pain; 4—6 refers to moderate pain; 7—10 refers to severe pain [ 8 ]. The criteria of analgesic efficacy evaluation included: 1 complete remission: painless, 2 partial remission: NRS score down to 1—3, 3 mild remission: NRS score down to 4—6, 4 non-remission: stable or incremental NRS score. To examine the stability of the model to alternative input parameters and assumptions, we conducted sensitivity analysis.
Here, individual parameters were varied independently with the usual convention being that both a value less than and a value higher than the base-case input parameters were tasted. We summarized the results of sensitivity analysis by examining the effect of changing parameter values or assumptions on the total costs of treatment.
Monte Carlo Simulation was conducted to analysis sensitivity of probability [ 19 , 20 ]. Cost-effectiveness acceptability curve and cost-effectiveness scatterplot were displayed. The search identified papers; after duplicates were removed, papers remained, with 81 papers included for full-text review, and 19 papers patients were included in this study [ 21 — 39 ]. Of the excluded papers, 20 papers adopted neither CR oxycodone nor SR morphine as comparison group.
The way of cancer pain titration reported in 23 papers could not meet our model, such as subcutaneous administration, drug combination, dosage reversed and cancer pain assessment with visual analog scale.
A flow chart describing study selection was presented in Fig 2. The risk of bias graph and the risk of bias summary for the included studies were described in Fig 3 , Fig 4. The funnel plots for assessment of publication bias were showed in Figs 5 — Two studies reported the pain control rate 97 patients [ 36 , 38 ]. As for SR morphine, the pain control rate were All of the included studies reported adverse drug reactions. CR oxycodone titration resulted fewer constipation Table 3.
The total costs of CR oxycodone group and SR morphine group were calculated at the events of 24h,48h,72h pain control and pain control failure after 72h separately. For each events, the total costs of CR oxycodone group were higher than SR morphine group. The pain control rate of cancer pain titration were Thousand samples were calculated by using Monte Carlo Simulation for our established decision tree. The simulation running results were shown as cost-effectiveness acceptability curve Fig 11 and cost-effectiveness scatter plot Fig Alternative assumptions and parameters were investigated in sensitivity analysis.
Three titration strategies were used to change the research assumption to test the stability of the results. If the initial titration dose of CR oxycodone is set at 10mg, the costs of CR oxycodone will reduced to a similar level of SR morphine Table 6.
The above mentioned variation of input parameter displayed minimal impact on the ICER. This is the first study to evaluate the economic of CR oxycodone compared with SR morphine in the treatment of cancer pain titration based on a decision tree model. Decision tree model increasingly use cost-effectiveness analysis to inform decision making on competing health care interventions. Economic models facilitate these analysis by providing a framework to combine information from different sources and enable probabilistic estimations.
Our cost-effectiveness analysis based on a decision tree model predicted the benefits of CR oxycodone compared with SR morphine for moderate to severe cancer pain titration.
The relative costs of cancer pain therapies has become an increasingly important issue in recent years due to growing concerns about the rising costs of health care and the lack of data demonstrating the superiority of one agent over another. The willingness-to-pay WTP threshold has not been officially defined in China, the general consensus is to be set at 1 gross domestic product GDP per capita, which is defined by the WHO [ 40 ]. Due to higher costs, CR oxycodone could not be deemed to be cost-saving.
Considering the heavy economic burden for patients associated with cancer treatment especially in antineoplastic drugs, the WTP of cancer pain titration may far less than 1GDP in developing country. SR morphine would be still a good choice for patient in financial straits. As a result of unique drug release technology of CR oxycodone, CR oxycodone may be better than SR morphine in cancer pain titration, but there was no evidence to support it.
At our knowledge, this is the first pharmacoeconomic study to support that perspective. The economic model established in this study can be generalized to other countries for cost-effectiveness analysis of opioid titration by inputting local data. For one-way sensitivity analysis, we further assumed that titration strategy would change in real world treatment. Despite this, CR oxycodone remained cost-effective. In addition, drug-acquisition costs was another crucial factor.
Hence, one-way sensitivity analysis demonstrated CR oxycodone was a cost-effective choice. It is true that there are methodological problems and a plethora of extraneous variables that influence the reliability and validity of studies conducted in pharmacoeconomic area [ 3 ].
Some limitations of our study need to be taken into account when interpreting the results. First, the use of efficacy data from two randomized control trials [ 36 , 38 ] may limit the ability to generalize the findings of this analysis to a broader population, and more up-to-date clinical data may be available.
Patients with cancer pain often receive concurrent chemotherapy or radiotherapy, which also have several side effects that can interfere with observation results of opioid adverse drug reactions. Most of the included studies did not describe whether patients received chemotherapy or radiotherapy during the cancer pain titration.
In addition, the included studies in our analysis did not have exactly the same titration strategy and course of treatment that may effect on adverse drug reaction rate and costs estimating. To account for such differences, we conducted several sensitivity analysis. We changed our assumptions of titration strategy to another three common modes and found CR oxycodone remained cost-effective in these conditions.
These titration strategies were discussed with clinical experts and were considered reasonable. Furthermore, the drug-acquisition costs of moderate to severe cancer pain titration were calculated. Due to the cancer pain was a complication in the cancer therapy, the cancer pain titration was implemented in conjunction with chemotherapy or radiotherapy.
The other hospitalization costs such as bed fee, chemotherapy fee, radiotherapy fee and indirect costs were not included in our analysis.
It is difficult to accurately quantify these costs especially in developing countries where there are limited research and data [ 3 ]. Considering the influence of drug price on results, we attempted to ascertain the impact of parameter variation via alternatives in a one-way sensitivity analysis.
In all the alternative scenarios conducted, the results were stable and consistent with base-case analysis. In our study, the cost-effectiveness was calculated based on the first three days of cancer pain titration.
So the costs were much lower than the reported in previous literatures. Finally, there are intrinsic biases that may influence the results. Potential bias could arise from study heterogeneity, such as in study population and study designs.
Then, the body becomes physically dependent on the drug to avoid going into opioid withdrawals. However, not all opioids are the same. Here are the most common opioids of abuse, listed from strongest to weakest.
Fentanyl is among the strongest and most dangerous opioids. It is 50 times more potent than heroin. However, it has become a very popular street drug of abuse. Due to its low cost and extremely high potency, street dealers often mix fentanyl with heroin, which can easily result in a fatal overdose.
If a person with little to no tolerance to opioids consumes the smallest amount of the substance, they are at serious risk for overdose. Heroin is derived from morphine and is the second strongest opioid. Although most opioids have a medical purpose — heroin does not. It is an illegal substance with a very high potential for abuse. Whether it is sold as a sticky black substance or a white or brown powder, heroin rapidly enters the bloodstream and causes intense feelings of euphoria.
Regardless if it is snorted, injected, or smoked, it is extremely dangerous and can result in an overdose. Heroin is particularly dangerous because it is manufactured in clandestine laboratories. Sometimes, it is cut with fentanyl or other dangerous substances. It can be difficult to tell exactly what chemicals are in different batches of heroin until it is too late.
Hydromorphone, or Dilaudid, is prescribed as a pain reliever for severe pain. Since it is significantly stronger than morphine, it produces relaxation and extreme sedation. The drug can be dissolved and injected, causing instant effects similar to those of heroin. Consequently, many people who suffer from an opioid use disorder will use hydromorphone as a substitute for heroin. Oxymorphone is sold under the brand name Opana.
Although it has medicinal use in treating moderate to severe pain, it still has a high potential for abuse. It is usually dispensed in pill form, however, it also comes as a liquid made for injection. Those who abuse oxymorphone might swallow the pills, snort them, or inject them.
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