Changes over time in prescription practices of pain medications in Switzerland between 2006 and 2013: an analysis of insurance claims

Analysis was done of insurance claims data from one of the major health insurers in Switzerland, the Helsana health insurance group. The insurer covers 1.2 million individuals (approximately one-sixth of the Swiss population) in all 26 cantons, and maintains records of all health care invoices including information about prescribed medications. The patient-level linked database provides information on socio-demographic data, health insurance status, prescribed drugs, health care utilization and its associated costs (inpatient, outpatient) as well as the date of death.

All administrative claims data of adults (age 18 years and older) who received reimbursement for at least one pain prescription between January 2006 and December 2013 were included in this analysis. All reimbursed medication claims are labeled with a unique code for the pharmaceutical class (see definitions). The code is based on the WHO pharmacological Anatomical Therapeutic Chemical (ATC) classification system [19]. Patients were identified by the ATC codes representing the following pain medications that were included in this analysis: non-opioids, weak opioids, and strong opioids.

In Switzerland compulsory basic health insurance is universal and covers the population of 8.2 million persons. There are virtually no uninsured residents. The basic health insurance covers a comprehensive benefits package defined by federal authorities and can be supplemented by private/semiprivate insurances that offer additional services [20]. The coverage provided through compulsory, individually purchased health insurance is a comprehensive benefit package that leads to out-of-pocket spending from copayments and deductibles [20]. The amount of copayment depends on the chosen deductible class. Several health care providers and payers are on the market and no centralized registration of prescriptions is available. Further, the 26 Swiss cantons are responsible for the planning and delivery of the health services and thus, the health care system is highly decentralized. Therefore, no centralized opioid use register is available. Opioids cannot be purchased over the counter and for strong opioids a special prescription (a so called “prescription for narcotic substances”) is issued on prescriptions with 3 copies including a unique identification number. One copy remains with the prescribing physician, one with the pharmacy and with the insurance company. While this regulation reduces the risk of abuse, there is no central database that would identify patients with multiple prescriber or other misuse.

Non-opioid pain medications: paracetamol (N02BE01, N02BE51, N02BE71), nonsteroidal anti-inflammatory drugs (NSAIDs, M01AA, M01AB, M01AC, M01AE, M01AG), cox-inhibitors (Coxibs, M01AH), metamizole (N02BB02, N02BB52, N02BB72).

Weak opioids included oral or rectal opioid formulations with a morphine conversion factor of 0.3 or less. ATC codes and substances for weak opioids were: N02AA59 (codeine and combinations), N02AX01 (tilidine), N02AX02 (tramadol), N02AX06 (tapentadol).

Strong opioids: all opioids not defined as weak. The full list of ATC codes, opioid substances, conversion factors, route of administration, and defined daily dose are provided in Additional file 1. In Switzerland hydrocodone (ATC code R05DA03) is not listed by the authorities and not covered by the basic insurance coverage and therefore, not included in this analysis. However, hydrocodone is in rare cases prescribed by physicians and a prescription for narcotic substances is required with the same regulation as described above.

Reimbursed pain medications: Each reimbursement of a pain medication (referred to hereafter as a “claim”) was converted to a total amount of substance by calculating the number of pills per reimbursement × strength of the substance. For each pharmaceutical class of pain medications, the total numbers of claims reimbursed, the average number of claims per person receiving pain medications, and the cumulative dose of milligrams (mg) of the active pharmaceutical substance were calculated and reported for each year between 2006 and 2013. Wherever available we calculate the cumulative dose per drug class: paracetamol, metamizole, weak opioids, strong opioids. For NSAIDs and Coxibs no dose conversion for individual formulations is available. Therefore, we report the cumulative dose per substance (e.g. diclofenac, ibuprofen) and depict selected substances.

Morphine equivalent dose (MED): To account for the different potencies of opioids, the morphine equivalent dose (MED) was calculated for each opioid (weak and strong) as follows: Strength of opioid drug in mg per unit x quantity of units per reimbursed package x number of packages x conversion factor for morphine equivalents. The equianalgesic dose conversions are only estimates and cannot account for individual variability in genetics and pharmacokinetics. Wherever available we used conversion factors provided by the Swiss Agency for Therapeutic Products (Swissmedic, agency comparable to the US Food and Drug Administration, FDA) or the morphine equivalent conversion factor per mg of opioid was based on the CONSORT classification (CONsortium to Study Opioid Risks and Trends [21]). Further, we consulted the literature relevant to the topic and a clinical pharmacologist (See Additional file 1: opioids, examples of brand names, the morphine equivalent conversion factors, and the route of administration). The MED calculation for fentanyl patches is based on the assumption that one patch delivers the dispensed (and bioavailable) mcg per hour over 72 h. The calculation of the total bioavailable MED dose in mg equals (mcg/hour (according to the package reimbursed) x 72 h’ x number of patches per package x number of packages reimbursed x 100 [fentanyl conversion factor])/1000. For example, the total MED in mg for one package containing 10 fentanyl patches that each delivers 12mcg per hour is calculated as follows: 12mcg x 72 h × 10 patches × 100 = 864,000mcg/1000 = 864 mg. For transdermal buprenorphine patches the assumption is that one patch delivers the dispensed (and bioavailable) mcg per hour over 96 h. The total MED dose in milligram equals (mcg/h according to the package reimbursed x 96 h’ x number of patches per package x number of packages reimbursed x 95 [buprenorphine conversion factor]) / 1000.

Defined daily dose (DDD): For strong opioids, treatment days were calculated by using the defined daily dose (DDD). The DDD is provided by the WHO ATC and is based on the assumed average maintenance dose per day for a drug used for its main indication in adults [19]. The WHO ATC/ DDD system allows standardization of drug groupings and a stable drug utilization metric to enable comparisons of drug use between countries [19].

Treatment days in MED: For strong opioids we calculated in addition to total MED the treatment days as follows: total MED per substance/DDD.

Morphine equivalent (MED) per treatment day: Total MED in mg/Total treatment days (for strong opioids).

Pain medication per 100’000 population: Reimbursed pain medications were extrapolated to calculate the amount of each pharmaceutical substance prescribed and the treatment days per 100’000 population.

Opioid substitution programs: Opioid substitution programs: We excluded patients using opioids within a drug substitution program. Since 1999, the insurance companies reimburse the opioids for drug substitution. We excluded diamorphine using the corresponding ATC-code (N07BC06 Diaphin®). Other opioids including morphine (N02AA01 Sevre-Long®), buprenorphine (N07BC01 Subutex®, N02AE01 Temgesic®), and methadone (N07BC02) are used within substitution programs and for pain treatment. For opioid dependency substitution a unique outpatient code is used (Tarmed Position 00.0155: non-physician medication distribution for opioid dependency substitution). We excluded all opioid claims from the analysis for all patients where this unique outpatient code was used at least once during the study period (e.g. in a patient the unique code was identified in the database in 2009 then all opioids reimbursed for this person were excluded).

Descriptive statistics included median and interquartile range for the continuous parameters, and percentages for the categorical outcomes. The annual number of claims and the cumulative dose of milligrams of the active pharmaceutical substance were extrapolated to calculate the amount of each pharmaceutical substance prescribed and the treatment days per 100’000 population stratified by age (strata of 5 years), gender, and canton using methods proposed for the analysis of complex survey analysis [22]. The age-dependent use of pain medications was studied by calculating the mean annual dose per patient between 2006 and 2013 in the following predefined age groups: 45 years or younger (reference category), 46 to 65, 66 to 75, 76 to 85, and 86 years and older.

Statistical analysis was performed using the computing environment R, a freely available system for statistical computation and graphics environment (https://​www.​r-project.​org/​) [23]. The following software packages were used: DescTools, mvtnorm, foreign, Rcpp, RDCOMClient, and tcltk.