Descriptive study of the real-world, long-term cost estimates and duration of use for hormonal and nonhormonal intrauterine devices using US commercial insurance claims.

BACKGROUND: Intrauterine devices (IUDs) have comparable efficacy to permanent surgical contraceptive methods; however, long-term costs are infrequently considered. Existing estimates inconsistently account for costs outside of IUD insertion or removal, actual duration of use, or differences between hormonal and nonhormonal IUDs. OBJECTIVE: To describe health care resource utilization and commercial payer costs that arise throughout hormonal and nonhormonal IUD use. METHODS: In this retrospective cohort study, paid claims data (Merative, MarketScan) from a large US commercial claims database were evaluated between 2013 and 2019. Claims were included from individuals aged 12 to 45 years who had an IUD inserted in 2014, continuous insurance coverage for 1 year prior to insertion and throughout follow-up, and no insertion, removal, or reinsertion in the previous year. Procedures and services that could be IUD-related were identified using Current Procedural Terminology and International Classification of Diseases, Ninth and Tenth Edition codes. Duration of IUD use was evaluated by Kaplan-Meier analysis of time to IUD removal. Event rates were determined for identified procedures and services; costs were calculated as the sum of payer reimbursements per enrolled individual. All IUD types available during the study period were described: 2 hormonal IUDs (52-mg and 13.5-mg levonorgestrel-releasing [LNG]) and the nonhormonal (380-mm2 copper) IUD. RESULTS: Of 195,009 individuals meeting the age requirement and receiving an IUD in 2014, 63,386 met the inclusion criteria and 53,744 had their IUD type on record-42,777 (67.5%) 52-mg LNG, 2,932 (4.6%) 13.5-mg LNG, and 8,035 (12.7%) nonhormonal IUD users. Despite differences in their indicated duration (13.5-mg LNG, 3 years; 52-mg LNG, 5 years; and nonhormonal, 10 years), most individuals had their IUD removed before its indicated full duration of use (13.5-mg LNG, 56.1%; 52-mg LNG, 61.3%; nonhormonal [at 5 years], 54.6%). The event rate per 100 individuals during the follow-up period was highest for abnormal uterine bleeding (16.2), ovarian cysts (9.3), and surgical management of uterine perforations (4.5). IUD insertion costs (mean ± SE) per enrolled individual for the 13.5-mg LNG, 52-mg LNG, and nonhormonal IUDs were $931 ± $9, $1,107 ± $4, and $897 ± $6, respectively. Cumulative mean ± SE 5-year postinsertion costs for the 13.5-mg LNG, 52-mg LNG, and nonhormonal IUDs were $2,892 ± $232, $1,514 ± $31, and $1,389 ± $97, respectively, among the remaining enrolled individuals. CONCLUSIONS: In this descriptive study of commercially insured IUD users, at least half had their IUD removed before its indicated duration. IUD improvements that reduce the frequency of abnormal uterine bleeding, ovarian cysts, and uterine perforations may help reduce long-term IUD costs.

The prevalence of opioid-related major potential drug-drug interactions and their impact on health care costs in chronic pain patients.

BACKGROUND: Literature has shown that chronic pain patients prescribed opioids are at an increased risk for experiencing drug-drug interactions as a result of polypharmacy. In addition, chronic, noncancer pain patients who experience drug-drug interactions have been shown to have greater health care utilization and costs. However, no study has focused on the health economics of major clinically significant drug-drug interactions associated with long-acting opioids. OBJECTIVES: To (a) estimate the prevalence of major drug-drug interactions among patients prescribed a long-acting opioid and (b) evaluate the potential impact of major drug-drug interactions on health care costs. METHODS: This study was a retrospective cohort analysis using claims data from the MarketScan Commercial Claims and Encounter Database between 2008 and 2010. Patients with at least 1 prescription for a long-acting opioid for ≥ 30 days were placed into cohorts according to the expected clinical impact of the potential drug-drug interaction: major versus none. Propensity score matching was used to mitigate differences in baseline characteristics between the cohorts. Health care costs were based on payments for all covered health care services, which consisted of inpatient and outpatient medical, emergency department, and outpatient prescription costs. RESULTS: Among 57,752 chronic, noncancer pain patients who met all inclusion and exclusion criteria, 5.7% (3,302) were exposed to a potential major drug-drug interaction. The costs associated with a potential interaction versus no potential interaction were significantly more after baseline characteristics of the cohorts were normalized by propensity score matching. Monthly health care costs in the 90-day post-index period were significantly greater ($3,366 vs. $2,757, a $609 difference) in patients exposed to a potential drug-drug interaction of major clinical significance, compared with those not exposed to a drug-drug interaction. The higher health care costs were mainly driven by outpatient and inpatient medical costs. CONCLUSIONS: Exposure to potential drug-drug interactions may result in unnecessary and unintended health care costs. Physicians should be made aware of commonly administered cytochrome P450 (CYP450) metabolized drugs in the chronic pain patient and consider prescribing non-CYP450 metabolized opioid and nonopioid analgesics. Managed care's use of utilization management tools to avoid these exposures may reduce costs.

Economic implications of potential drug-drug interactions in chronic pain patients.

Chronic pain patients may be subject to polypharmacy because of long-term pharmacological pain treatment and additional comorbidities. Many chronic pain patients expose themselves to potential drug-drug interactions (DDIs) and these interactions can have unintended and severe consequences. Prevalence and costs associated with DDIs are inconsistent and has led to an inadequate level of awareness among the medical community; therefore, it has become necessary to re-evaluate the rates of DDIs in chronic pain patients. Utilizing medical and prescription claims databases, five studies were conducted to assess the health care utilization of and associated financial payments for patients >18 years with chronic noncancer pain. The studies evaluated drug-drug exposures with the potential to cause DDIs specifically occurring through the CYP450 enzyme system. The studies reported that drug-drug exposures are prevalent, costly and can occur in any age group and that physicians should consider ways to limit their patients' exposure to potential DDIs.

Development of a questionnaire to assess the impact of chronic low back pain for use in regulated clinical trials.

BACKGROUND: Chronic low back pain (CLBP) is the most common chronic pain condition and is associated with clinical, economic, social, and public health impacts. The effect of CLBP on patients' health-related quality of life (HRQoL) is significant. The symptoms and impacts most often associated with CLBP include pain and disability; patients most affected are often crippled by the condition. CLBP also affects patients' mental, physical, and psychosocial well-being. A variety of self-report measures have been developed for the assessment of CLBP, such as the Roland Morris Disability Questionnaire (RMDQ); however, existing measures may not meet current regulatory expectation for the development, documentation, and use of patient-reported outcomes (PRO) questionnaires (U.S. Department of Health and Human Services, Food and Drug Administration, 2009). OBJECTIVES: This report describes the qualitative development of the Chronic Low Back Pain Impact Questionnaire (CLBP-IQ), created for use in clinical trials. METHODS: A total of 22 CLBP patients recruited by clinicians participated in concept elicitation interviews to identify target measurement concepts. An instrument development team generated the instructions, items, and response options guided by patient input. Cognitive debriefing interviews were conducted with 21 patients recruited by the same clinicians who recruited for concept elicitation interviews. During cognitive interviews, a draft instrument composed of 28 items was presented to individuals with CLBP to evaluate its readability and comprehensiveness. All research activities were conducted in the US. RESULTS: During concept elicitation interviews, participants reported a variety of physical, emotional, and social impacts associated with CLBP. Participants also reported CLBP impacts on sleep, energy, daily activities, work, household activities, leisure activities, cognition, self-care, and sex life. Impacts deemed simple, important, and relevant to CLBP patients became targets of measurement for the CLBP-IQ. During cognitive debriefing, seventeen items were interpreted as intended by at least 90 % of participants, and no items were interpreted incorrectly by more than five patients (24 %). Additionally, seventeen items were experienced by at least 90 % of participants, and no single item was experienced by less than 67 % of participants (n = 14). CONCLUSIONS: The CLBP-IQ was developed in accordance with current US Food and Drug Administration guidance on instrument development. Results from both concept elicitation and cognitive debriefing interviews support the content validity of the CLBP-IQ in patients with CLBP. Future development should proceed with psychometric evaluation.

Estimated economic benefits from low-frequency administration of atypical antipsychotics in treatment of schizophrenia: a decision model.

The objective of this study was to quantify the direct medical resources used and the corresponding burden of disease in the treatment of patients with schizophrenia. Because low-frequency administration (LFA) of risperidone guarantees adherence during treatment intervals and offers fewer opportunities to discontinue, adherence and persistence were assumed to improve, thereby reducing relapses of major symptoms.A decision tree model including Markov processes with monthly cycles and a five-year maximum timeframe was constructed. Costs were adapted from the literature and discounted at a 3% annual rate. The population is a demographically homogeneous cohort of patients with schizophrenia, differentiated by initial disease severity (mildly ill, moderately ill, and severely ill). Treatment parameters are estimated using published information for once-daily risperidone standard oral therapy (RIS-SOT) and once-monthly risperidone long-acting injection (RIS-LAI) with LFA therapy characteristics derived from observed study trends. One-year and five-year results are expressed as discounted direct medical costs and mean number of relapses per patient (inpatient, outpatient, total) and are estimated for LFA therapies given at three, six, and nine month intervals.The one-year results show that LFA therapy every 3 months (LFA-3) ($6,088) is less costly than either RIS-SOT ($10,721) or RIS-LAI ($9,450) with similar trends in the 5-year results. Moreover, the model predicts that LFA-3 vs. RIS-SOT vs. RIS LAI therapy will reduce costly inpatient relapses (0.16 vs. 0.51 vs. 0.41). Extending the interval to six (LFA-6) and nine (LFA-9) months resulted in further reductions in relapse and costs.Limitations include the fact that LFA therapeutic options are hypothetical and do not yet exist and limited applicability to compare one antipsychotic agent versus another as only risperidone therapy is evaluated. However, study results have quantified the potential health state improvements and potential direct medical cost savings achievable with the development and use of LFA medication delivery technologies.

Development of a men's Preference for Testosterone Replacement Therapy (P-TRT) instrument.

BACKGROUND: This study used a standard research approach to create a final conceptual model and the Preference for the Testosterone Replacement Therapy (P-TRT) instrument. METHODS: A discussion guide was developed from a literature review and expert opinion to direct one-on-one interviews with participants who used testosterone replacement therapy and consented to participate in the study. Data from telephone interviews were transcribed for theme analysis using NVivo 9 qualitative analysis software, analyzed descriptively from a saturation grid, and used to evaluate men's P-TRT. Data from cognitive debriefing for five participants were used to evaluate the final conceptual model and validate the initial P-TRT instrument. RESULTS: Item saturation and theme exhaustion was achieved by 58 male participants of mean age 55.0 ± 10.0 (22-69) years who had used testosterone replacement therapy for a mean of 175.0 ± 299.2 days. The conceptual model was developed from items and themes obtained from the participant interviews and saturation grid. Items comprising eight dimensions were used for instrument development, ie, ease of use, effect on libido, product characteristics, physiological impact, psychological impact, side effects, treatment experience, and preference. Results from the testosterone replacement therapy preference evaluation provide a detailed insight into why most men preferred a topical gel product over an injection or patch. CONCLUSION: Items and themes relating to use of testosterone replacement therapy were in concordance with the final conceptual model and 29-item P-TRT instrument. The standard research approach used in this study produced the P-TRT instrument, which is suitable for further psychometric development and use in clinical practice.

Economic impact of potential drug-drug interactions among osteoarthritis patients taking opioids.

Patients with osteoarthritis (OA) taking at least one CYP450-metabolized opioid concurrently with another CYP450-metabolized medication experience a drug-drug exposure (DDE), which puts them at risk of a pharmacokinetic drug-drug interaction (PK DDI). This study compared patients with and without such an incident DDE to determine healthcare utilization and associated payments. Using a retrospective database analysis, the impact of DDEs was evaluated in terms of associated clinical events, healthcare services utilization (office visits, outpatient visits, ED visits, hospitalization), and payments in patient populations based on age (those under age 65 and those 65 years of age and older), during the 6 months after exposure. DDE patients had significantly more inpatient hospitalizations than no-DDE patients. Mean total payments at 6 months were significantly higher for both younger and older patients with DDE compared to similar patients without DDE ($9,469, SD = $12,192 vs. $8,382, SD = $14,078, respectively, for younger patients, resulting in a difference of $1,087, P < 0.004, and $9,829, SD = $11,721 vs. $8,622, SD = $10,131, respectively, for older patients, resulting in a difference of $1,207, P = 0.001). In both age groups, DDE patients had significantly higher payments for nonopioid prescription drugs ($1,824 SD = $2,420 vs. $1,362, SD = $1,891, respectively, for younger patients, resulting in a difference of $462, P < 0.001, and $2,197 SD = $2,332 vs. $2,013, SD = $2,437, respectively, for older patients, resulting in a difference of $184, P = 0.020). Overall, patients with OA who experienced DDEs had significantly greater utilization rates of healthcare resources and higher associated payments in the 6-month observation period following the exposure, compared to patients without DDEs, consistent with the risk of PK DDIs associated with DDEs.

Economic impact of potential CYP450 pharmacokinetic drug-drug interactions among chronic low back pain patients taking opioids.

Chronic low back pain (cLBP) patients who take at least 1 CYP450-metabolized opioid analgesic agent concurrent with at least 1 other CYP450-metabolized medication experience a drug-drug exposure (DDE), which puts them at risk for a pharmacokinetic drug-drug interaction (PK DDI). This study compared utilization of healthcare resources and associated payments in cLBP patients with and without incident DDEs with the potential to cause PK DDIs. A retrospective database analysis examined the associated clinical events, healthcare utilization (measured in terms of claims for office visits, outpatient visits, emergency department visits, and hospitalization), and cost to the health plan, as defined as the sum of health plan payments for resources used. Patients were grouped into 2 cohorts by age (those under 65 and those 65 years and over). In the 6 months after exposure, total healthcare payments were significantly higher for DDE patients than those without DDEs (no-DDE), in both in the younger ($7,086, SD = $8,370) and $6,353, SD = $8,352, respectively, P < 0.001) and the older cohorts ($7,806 vs. $7,043, respectively, P = 0.013). Younger and older patients with DDE had significantly higher prescription payments than those without DDE ($2,041, SD = $2,706 vs. $1,565, SD = $2,349, respectively, P < 0.001 for younger and $2,482, SD = $2,481 vs. $2,286, SD = $2,521, respectively, P = 0.044 for older patients). Both older and younger patients with DDE had significantly more claims for office visits and higher associated payments than similar patients without DDE. Patients in the study who experienced DDEs that placed them at risk for PK DDIs had significantly greater utilization rates of healthcare resources and higher associated payments in the 6-month observation period following exposure.

Direct and indirect costs of patients treated with extended-release oxymorphone HCl or controlled-release oxycodone HCl.

OBJECTIVE: Compare direct and indirect costs of oxymorphone extended-release ('oxymorphone') and oxycodone controlled-release ('oxycodone') users. METHODS: Patients, aged 18+, with ≥1 claim for oxymorphone/oxycodone, Q2:2006-Q4:2009, were selected from a de-identified private payer claims database and observed from the first such claim ('index date') until the earliest of: use of comparator drug; end of continuous eligibility; 12 months ('study period'). Patients with claims for any formulation of the comparator drug during the first 30 days of the study period were excluded. Direct (medical and drug) costs paid by private insurers were reported for patients aged 18-64 (n = 8354) and 65+(n = 3515), as well as sub-sets without cancer (n = 7090 and n = 2444, respectively). Indirect costs (medically-related absenteeism and disability) were reported for all employees, aged 18-64 (n = 1313), and employees without cancer (n = 1146). Multivariate models were used to estimate risk-adjusted costs controlling for patient characteristics. RESULTS: Oxymorphone users, aged 18-64, had lower drug costs ($693 vs $763, p = 0.0035) and similar medical costs ($1875 vs $1976, p = 0.3570) per patient-month compared with oxycodone users (mean follow-up 236 and 280 days, respectively). Indirect costs were not different ($662 vs $670, p = 0.9370). Oxymorphone users, aged 65+, had similar Medicare supplemental drug costs ($533 vs $588, p = 0.0840) and lower medical costs ($459 vs $747, p < 0.0001). Results were comparable for subsets without cancer. LIMITATIONS: Patients with concomitant use of oxymorphone and oxycodone were excluded. CONCLUSIONS: Oxymorphone users incur lower risk-adjusted costs in several cost categories, compared with oxycodone users, and no higher costs in any of the examined categories.

Daily average consumption of 2 long-acting opioids: an interrupted time series analysis.

BACKGROUND: Oxycodone controlled release (CR) and oxymorphone extended release (ER) are frequently prescribed long-acting opioids, which are approved for twice-daily dosing. The US Food and Drug Administration approved a reformulated crush-resistant version of oxycodone CR in April 2010. OBJECTIVE: To compare the daily average consumption (DACON) for oxycodone CR and for oxymorphone ER before and after the introduction of the reformulated, crush-resistant version of oxycodone CR. METHODS: This was a retrospective claims database analysis using pharmacy claims from the MarketScan database for the period from January 2010 through March 2011. The interrupted time series analysis was used to evaluate the impact of the introduction of reformulated oxycodone CR on the DACON of the 2 drugs-oxycodone CR and oxymorphone ER. The source of the databases included private-sector health data from more than 150 medium and large employers. All prescription claims containing oxycodone CR and oxymorphone ER dispensed to members from January 1, 2010, to March 31, 2011, were included in the analysis. Prescription claims containing duplicate National Drug Codes, missing member identification, invalid quantities or inaccurate days supply of either drug, and DACON values of <1 and >500 were removed. RESULTS: The database yielded 483,063 prescription claims for oxycodone CR and oxymorphone ER from January 1, 2010, to March 31, 2011. The final sample consisted of 411,404 oxycodone CR prescriptions (traditional and reformulated) dispensed to 85,150 members and 62,656 oxymorphone ER prescriptions dispensed to 11,931 members. Before the introduction of reformulated oxycodone CR, DACON values for the highest strength available for each of the 2 drugs were 0.51 tablets higher for oxycodone CR than for oxymorphone ER, with mean DACON values of 3.5 for oxycodone CR and 3.0 for oxymorphone ER (P <.001). The differences of mean DACON between the 2 drugs for all lower strengths were 0.46 tablets, with mean DACON values of 2.7 for oxycodone CR and 2.3 for oxymorphone ER (P <.001). After the introduction of the new formulation, the difference in mean DACON between the 2 drugs was slightly lower: 0.45 tablets for the highest-strength and 0.40 tablets for the lower-strength pairs. Regression analyses showed that the immediate and overall impact of the reformulation of oxycodone CR on the DACON of oxycodone CR was minimal, whereas no changes were seen in the DACON of oxymorphone ER. The estimated DACON for oxycodone CR decreased by 0.1 tablets, or 3.7% (P <.001), 6 months after the new formulation was introduced. CONCLUSION: The mean DACON was 0.4 tablets per day higher for oxycodone CR compared with oxymorphone ER for all dosage strengths for the entire study period. After the introduction of the reformulated oxycodone CR, the DACON for this drug was slightly mitigated; however, there was a minimal impact on the mean differences between oxycodone CR and oxymorphone ER.

A comparison of daily average consumption (DACON) of oxycodone and oxymorphone long-acting oral tablets.

BACKGROUND: The utilization of high-potency opioids is an important component of chronic pain management, and appropriate utilization of these medicines is a common concern of payers. Two of the most commonly prescribed oral long-acting opioids, oxycodone controlled-release (CR) and oxymorphone extended-release (ER), are FDA-approved for twice-daily dosing, which equates to a theoretical average consumption (DACON) of 2 tablets per day. DACON values greater than 2 have budget and policy implications for managed care pharmacists. OBJECTIVES: To assess from the perspective of the pharmacy benefit decision maker the DACONs of oxycodone CR and oxymorphone ER. METHODS: The main outcome measure for the analysis was DACON. Pharmacy and medical claims data from a large commercially insured population (i3 InVision Data Mart database) were analyzed to identify patients with at least 1 pharmacy claim for either oxycodone CR or oxymorphone ER from July 1, 2007, to September 30, 2009. After an initial 30-day titration period, all subjects included in the study had 1 or more claims totaling at least a 90-day supply of either study drug during the subsequent 90 days (DACON measurement period). Patients were excluded if there was evidence of a switch from one to the other study opioid during the 90-day measurement period. There were no limitations on the use of other opioids, either short- or long-acting, during either the DACON measurement period or the previous 6 months (baseline period). In addition, patients were excluded if the enrollee was younger than 18 years old, pregnant, did not have continuous insurance coverage for the 6 months before and after the start of the 90-day DACON measurement, or were enrolled in an HMO plan. Bivariate analyses were performed with between-group differences in DACON values assessed using t-tests and Wilcoxon rank sum tests. Patient characteristics including age, sex, geographic location, and baseline Charlson Comorbidity Index (CCI) for each drug group were evaluated descriptively using either the Pearson chi-square test or t-test. Multivariate analyses were conducted using generalized linear models (GLM) to adjust for the observed heterogeneity among patients in the observational database. For the GLMs, the gamma distribution and log link function were chosen to account for non-normal distributions of DACON. Independent variables included study drug, tablet strengths, age, sex, CCI, the maximum days gap between prescription refills during the DACON measurement period, and other opioid medication use. Several sensitivity analyses were conducted to verify all findings. RESULTS: The final analyses were conducted on 6,567 oxycodone CR patients and 796 oxymorphone ER patients. The unadjusted DACON mean value for the highest strength of oxycodone CR 80 milligrams (mg) was 3.9, compared with 2.9 for oxymorphone ER 40 mg (P < 0.001); mean DACON values were 3.0 versus 2.4, respectively, for lower strengths (P < 0.001) and 3.1 versus 2.5 for all strengths (P < 0.001). After adjusting for age, sex, CCI, maximum gap days, and other opioid medication use, a risk-adjusted mean difference in DACON remained, with oxycodone CR patients receiving on average 0.6 tablets more per day than those dispensed oxymorphone ER (P < 0.001). The direction, magnitude, and statistical significance of these differences were essentially unchanged in sensitivity analyses. CONCLUSIONS: On average during a 90-day time period, patients taking oxymorphone ER consumed 0.6 fewer tablets per day than did patients taking oxycodone CR. Further research is necessary to see if this difference amounts to cost savings for health plans that provide prescription reimbursement for patients with chronic pain syndromes.

Economic impact of potential drug-drug interactions in opioid analgesics.

OBJECTIVE: Patients managing chronic non-cancer pain with cytochrome P450 (CYP450)-metabolized opioid analgesics who concurrently take another CYP450-metabolized medication experience a drug-drug exposure (DDE), which puts them at risk for a pharmacokinetic drug-drug interaction (PK DDI). This study examined the economic impact of incident DDEs with the potential to cause PK DDIs compared to similar patients without such exposure. STUDY DESIGN: This retrospective analysis used paid claims from a large, commercially insured population during January 1, 2004 through December 31, 2008. METHODS: Propensity matching was used to control for baseline differences in comparisons between 85,043 exposed and 85,043 non-exposed patients. RESULTS: Comparisons yielded mean total costs 6 months after the DDEs that were significantly higher in subjects with DDE versus matched subjects without DDE [$8165 (SD $11,357) vs. $7498 (SD $11,668), respectively, p<0.01] resulting in a difference of $667. This was driven by medical costs [$5520 (SD $10,505) vs. $5222 (SD $10,689), respectively, p<0.01] a $298 difference, and total prescription costs [$2646 (SD $3262) vs. $2276 (SD $3907), respectively, p<0.01] a $369 difference. LIMITATIONS: The study design demonstrates associations only and cannot establish causal relationships. Further, relevant DDEs were not included if concurrent consumption occurred outside the index period and when CYP450 substances were consumed that are not reflected in pharmacy claims (herbals, over-the-counter medications). CONCLUSION: Since concurrent exposure to DDEs with the potential to cause PK DDIs may be relatively common, policy decisions-makers should consider the use of long-acting opioids that are not metabolized through the CYP450 pathway.

Exposure to potential CYP450 pharmacokinetic drug-drug interactions among osteoarthritis patients: incremental risk of multiple prescriptions.

Patients taking more than one drug metabolized through the cytochrome P450 (CYP450) enzyme system experience a drug-drug exposure (DDE), which puts them at risk for a potential pharmacokinetic drug-drug interaction (DDI), defined as two or more drugs interacting in such a way that the effectiveness and/or toxicity of one or all drugs are changed. Any patient subjected to a DDE is at risk for a potentially serious DDI, the epidemiology of which has not been thoroughly studied. Many drugs are metabolized primarily via the CYP450 enzyme system, including certain opioids used to manage moderate to severe chronic pain. We conducted a retrospective analysis of a large commercial claims database and a Medicare database to assess the prevalence of DDEs among patients with osteoarthritis taking CYP450-metabolized opioids. The overall prevalence of DDEs in this population was 26%, with females more likely to experience DDEs than males (28.4% vs. 21.0%, respectively). The number of unique concurrent prescriptions at baseline, gender, age, and Charlson Comorbidity Index were statistically significant predictors of DDEs (P < 0.05). This study challenged previous assumptions about DDEs in that advanced age was not positively associated with the risk of DDE. However, the number of prescriptions the patient received in the 90-day window prior to the index date was a risk factor. For patients taking at least two medications in the 90-day period prior to the index date, every additional prescription taken increased their risk for a DDE during the observation period by 138% (on average). The risk of DDE during the study period was threefold greater for patients with one medication in the 90-day period before index date compared with similar patients with no prescriptions in that same period before the index date. DDEs are more common than may be generally believed in patients with osteoarthritis, regardless of age, and can occur even in patients taking few medications. When selecting an opioid analgesic to treat osteoarthritis, physicians should consider the potential for exposure of these patients to drugs that could interact unfavorably.

Prevalence of exposure to potential CYP450 pharmacokinetic drug-drug interactions among patients with chronic low back pain taking opioids.

Drug-drug interactions (DDIs) have been defined as two or more drugs interacting in such a way that the effectiveness and/or toxicity of one or all drugs are changed. Patients taking more than one drug metabolized through the cytochrome P450 (CYP450) enzyme system, including some, but not all, opioids experience a drug-drug exposure (DDE), which may result in a potentially dangerous DDI. Using a retrospective analysis of a large commercial claims database and a Medicare database, we evaluated DDEs that have the potential to cause DDIs among chronic low back pain (cLBP) patients on long-term opioid analgesia, which metabolizes through the CYP450 enzyme system, concomitant with other CYP450-metabolized drug(s). The overall prevalence of DDEs among cLBP patients was 27%. Women had a higher prevalence of DDEs (30.6% vs. 22% for men). Patients aged 45 to 55 and 56 to 64 years had the highest prevalence of DDEs (30.4% and 29.8%, respectively), followed by patients 34 to 45 years (27.9%). For patients>65 years, the prevalence of DDEs was 23.1%. In general, the prevalence of DDEs was fairly consistent across age ranges in this population. This study suggests that DDEs are common in the cLBP population. When selecting an opioid to treat cLBP, physicians should consider the potential for exposure of these patients to drugs that might unfavorably interact and, for that reason, the use of opioids that do not rely on the CYP450 system as their primary means of metabolism might be worthy of consideration.

Comparing healthcare costs of Medicaid patients with postherpetic neuralgia (PHN) treated with lidocaine patch 5% versus gabapentin or pregabalin.

OBJECTIVE: To compare healthcare resource utilization and costs of postherpetic neuralgia (PHN) patients initiating lidocaine patch 5% (lidocaine patch) or oral gabapentin/pregabalin. METHODS: Patients with PHN diagnosis, or herpes zoster diagnosis and ≥30 days PHN-recommended treatment were selected from de-identified Medicaid claims data from Florida, Iowa, Missouri, and New Jersey, 1999-2007. Patients initiated monotherapy with lidocaine patch or gabapentin/pregabalin after PHN diagnosis, had continuous eligibility 6 months before (baseline) and 6 months after (study period) medication index date, and were ≥18 years old. Lidocaine patch patients were matched to gabapentin/pregabalin patients based on their propensity to initiate treatment. Study period resource utilization and costs from a Medicaid perspective were compared between treatment groups using univariate analysis. RESULTS: Matched patients were on average 61.3 years old, approximately 73% were women, and 55% had other painful conditions during the baseline period. 6-month per patient PHN-related prescription drug costs were similar for matched lidocaine patch (n=312) and gabapentin/pregabalin (n=312) patients ($854 vs. 820, p=0.75), while PHN-related medical costs appeared lower in the lidocaine patch group ($145 vs. 353, p=0.12). Furthermore, there were no statistically significant differences between treatment groups during the observation period in overall resource utilization, total prescription drug costs, and total medical costs per patient. CONCLUSIONS: In spite of higher list prices, PHN patients treated with lidocaine patch cost no more than patients treated with gabapentin or pregabalin in terms of overall healthcare costs over the 6-month study period. The study suggests that PHN-related medical costs may be lower among lidocaine patch patients. LIMITATIONS: Findings are based on a Medicaid sample and may not be generalizable to all PHN patients.

Descriptive analysis of Medicaid patients with postherpetic neuralgia treated with lidocaine patch 5%.

OBJECTIVES: To compare demographic and comorbidity profiles and healthcare costs of Medicaid patients with postherpetic neuralgia (PHN) treated with lidocaine patch 5% (lidocaine patch) versus patients not treated with the lidocaine patch. Repeat comparison for the subset of patients treated in long-term care (LTC) settings. METHODS: Patients, age≥18 years, with PHN diagnosis, or PHN-likely patients with herpes zoster diagnosis and ≥30 days of PHN-recommended treatment, were identified in Medicaid claims from Florida, Iowa, Missouri, and New Jersey (1999-2007). Patients had continuous eligibility 6 months before (baseline) and 12 months after (study period) the PHN index date. Patients with ≥1 claim for a lidocaine patch during the study period (n=872) were compared to patients without a lidocaine patch claim (comparison group). Baseline characteristics, study period treatment and healthcare costs (reimbursements by Medicaid for medical services and prescription drugs) were compared between groups using univariate analyses. RESULTS: PHN patients in the lidocaine patch group were older (64.5 vs. 62.2 years; p=0.002) and had higher rates of pain-related comorbidities (e.g., back/neck pain, osteoarthritis) than comparison patients. Average PHN-related drug costs per patient were higher ($1994 vs. 1137; p<0.0001) among lidocaine patch patients, with lidocaine patch accounting for $505 of the difference. PHN-related medical costs appeared lower in the lidocaine patch group, although not statistically significant ($983 vs. 1294; p=0.1348). No significant differences were found in total healthcare costs ($20,175 vs. 19,124; p=0.3720) across groups, despite higher total prescription drug costs among lidocaine patch patients. A similar pattern was observed among LTC patients. CONCLUSIONS: Despite higher rates of comorbidities and prescription drug costs, lidocaine patch patients had similar study period healthcare costs as comparison patients. The cost of the lidocaine patch represented a small fraction of overall costs incurred over the study period. LIMITATIONS: Findings are based on a Medicaid sample and may not be generalizable to all PHN patients.

Predicting EQ-5D utility scores from the 25-item National Eye Institute Vision Function Questionnaire (NEI-VFQ 25) in patients with age-related macular degeneration.

PURPOSE: In this study, we explored different statistical approaches to identify the best algorithm to predict EQ-5D utility scores from the NEI-VFQ 25 in patients with age-related macular degeneration (AMD). METHODS: Ordinary least squares (OLS), Tobit, and censored least absolute deviation (CLAD) approaches were compared using cross-sectional data (primary dataset, n = 151) at screening from a phase I/II clinical trial in patients with AMD. Three models were specified in this study: full (includes all 12 dimensions of the NEI-VFQ 25), short (includes only the general health dimension and the composite score), and reduced model (using stepwise regression). To evaluate the predictive accuracy of the models, the mean absolute prediction error (MAPE), mean error, and root means squared error were calculated using in-sample cross-validation (within the primary dataset) and out-of-sample validation using an independent dataset (n = 393). The model that provided the lowest prediction errors was chosen as the best model. RESULTS: In-sample cross-validation and out-of-sample validation consistently demonstrated that, compared to other approaches, heteroscedasticity-adjusted OLS produced the lowest MAPE (mean values were 0.1400, 0.1593, respectively) for the full model, while CLAD performed best for the short and reduced models (mean values were 0.1299, 0.1483, respectively). The normality and homoscedasticity assumptions of both OLS and Tobit were rejected. CLAD, however, can accommodate these particular violations. CONCLUSIONS: The CLAD-short model is recommended for producing the EQ-5D utility scores when only the NEI-VFQ 25 data are available.