An accelerated pathway for targeted cancer therapies.

A well-defined pathway for the accelerated development and approval of targeted cancer therapies and companion diagnostics would reduce uncertainty, improve efficiency in development and provide an effective incentive for developers.

A large observational study of cardiovascular outcomes associated with atorvastatin or simvastatin therapy in hypertensive patients without prior cardiovascular disease.

The objective of this study was to examine whether differences in effectiveness exist between statins in hypertensive patients seen in clinical practice. We assessed cardiovascular (CV) outcomes in hypertensive patients without cardiovascular disease who began therapy with atorvastatin (10 or 20 mg/d) or simvastatin (20 or 40 mg/d) between January 1, 2003, and September 30, 2005, using claims data from 92 US managed care plans in the PharMetrics database. A total of 98,471 hypertensive patients were identified, comprising 74,685 atorvastatin users (mean dose 13.6 mg/d) and 23,786 simvastatin users (mean dose 28.6 mg/d), and followed a median 1.5 years for the occurrence of a first CV event. The crude CV event rates were 2.81 and 3.92 per 100 person-years for atorvastatin and simvastatin, respectively [unadjusted hazard ratio (HR): 0.73; 95% confidence interval (CI): 0.68-0.78, P < 0.001]. After adjusting for clinical and demographic confounders, use of atorvastatin was associated with fewer CV events compared with simvastatin (HR: 0.91; 95% CI: 0.84-0.98, P = 0.009). However, the lipid-lowering efficacy of the 2 statins could not be assessed as patient lipid data were unavailable. In conclusion, hypertensive patients without cardiovascular disease who initiated atorvastatin (10 or 20 mg/d) had a significantly lower risk of subsequent CV events compared with those who initiated simvastatin at doses of similar potency (20 or 40 mg/d). As with all observational studies, the study is subject to certain limitations, and the findings should be regarded as hypothesis generating.

An evaluation of recent federal spending on comparative effectiveness research: priorities, gaps, and next steps.

The American Recovery and Reinvestment Act of 2009 included new funding for developing better evidence about health interventions, with a down payment of $1.1 billion for comparative effectiveness research. Our analysis of funds allocated in the legislation found that nearly 90 percent of the $1.1 billion will eventually be spent on two main types of activity: developing and synthesizing comparative effectiveness evidence, and improving the capacity to conduct comparative effectiveness research. Based on our analysis, priorities for the new funding should include greater emphasis on experimental research; evaluation of reforms at the health system level; identification of effects on subgroups of patients; inclusion of understudied groups of patients; and dissemination of results.

Comparative effectiveness research: Policy context, methods development and research infrastructure.

Comparative effectiveness research (CER) has received substantial attention as a potential approach for improving health outcomes while lowering costs of care, and for improving the relevance and quality of clinical and health services research. The Institute of Medicine defines CER as 'the conduct and synthesis of systematic research comparing different interventions and strategies to prevent, diagnose, treat, and monitor health conditions. The purpose of this research is to inform patients, providers, and decision-makers, responding to their expressed needs, about which interventions are most effective for which patients under specific circumstances.' Improving the methods and infrastructure for CER will require sustained attention to the following issues: (1) Meaningful involvement of patients, consumers, clinicians, payers, and policymakers in key phases of CER study design and implementation; (2) Development of methodological 'best practices' for the design of CER studies that reflect decision-maker needs and balance internal validity with relevance, feasibility and timeliness; and (3) Improvements in research infrastructure to enhance the validity and efficiency with which CER studies are implemented. The approach to addressing each of these issues should be informed by the understanding that the primary purpose of CER is to help health care decision makers make informed clinical and health policy decisions.

Does a single-pill antihypertensive/lipid-lowering regimen improve adherence in US managed care enrolees? A non-randomized, observational, retrospective study.

BACKGROUND: A previous study in 4703 patients suggested that a single-pill combination of amlodipine and atorvastatin is associated with greater adherence to therapy than a two-pill calcium channel antagonist (calcium channel blocker [CCB]) and HMG-CoA reductase inhibitor (statin) regimen. However, the impact of prior medication use on the potential adherence benefits of single-pill amlodipine/atorvastatin has not been studied. OBJECTIVE: To compare adherence to single-pill amlodipine/atorvastatin versus two-pill CCB + statin regimens in a large managed care population, stratified according to prior CCB and statin use. METHODS: This retrospective study was conducted among managed care enrolees in the US. Patients included in the analysis had to have a pharmacy claim for single-pill amlodipine/atorvastatin or claims for both a CCB and a statin within any 30-day window between April 2004 and April 2005. Adherence was measured over 6 months following the index date (the date of the first single-pill amlodipine/atorvastatin claim or of the claim for the second medication class for any two-pill CCB + statin regimen) as the proportion of days covered (PDC) by both CCB and statin therapy; patients were considered 'adherent' if PDC was > or =80%. Patients were divided into four cohorts based on pre-index CCB and statin use: (i) naive (CCB)/naive (statin); (ii) experienced (CCB)/naive (statin); (iii) naive (CCB)/experienced (statin); and (iv) experienced (CCB)/experienced (statin). Within each cohort, adherence was compared for patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin or other two-pill CCB + statin regimens (including amlodipine or atorvastatin but not both) at index. Multivariable logistic regression with propensity score weighting was used to adjust for covariates, including age, sex and co-morbidities. RESULTS: In total, 35,430 patients were included in the analysis. At month 6 (after adjusting for covariates), patients in the experienced (CCB)/naive (statin) cohort receiving single-pill amlodipine/atorvastatin were more than twice as likely to be adherent as those receiving two-pill amlodipine + atorvastatin (odds ratio [OR] 2.20; p < 0.0001) or other two-pill CCB + statin regimens (OR 2.75; p < 0.0001). Similarly, patients in the naive (CCB)/experienced (statin) cohort receiving single-pill amlodipine/atorvastatin were more likely to be adherent than those receiving two-pill amlodipine + atorvastatin (OR 1.72; p < 0.0001) or other two-pill CCB + statin regimens (OR 2.81; p < 0.0001). In contrast, in the naive (CCB)/naive (statin) cohort there was no significant difference in adherence between patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin (OR 1.00), although patients receiving single-pill amlodipine/atorvastatin were slightly more likely to be adherent than those receiving other two-pill CCB + statin regimens (OR 1.29; p < 0.01). In the experienced (CCB)/experienced (statin) cohort there was also no significant difference between patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin (OR 1.08), and only a slightly greater likelihood of achieving adherence to single-pill amlodipine/atorvastatin versus other two-pill CCB + statin regimens (OR 1.19; p < 0.01). CONCLUSIONS: This large retrospective study confirms previous observations that single-pill amlodipine/atorvastatin can help improve adherence versus two-pill CCB + statin regimens. However, greater improvements in adherence are likely to be observed in patients with prior experience of either CCB or statin therapy than in those either naive to, or experienced with, both therapies.

Propensity score matching in the evaluation of drug therapy management programs: an illustrative analysis of a program for patients with hepatitis C virus.

This retrospective cohort analysis demonstrates the application of propensity score methods in the Be In Charge (BIC) program, a drug therapy management program for patients with hepatitis C. Data were drawn from BIC participant records and program utilization and from a longitudinal database of administrative claims for pharmacy and medical services. Eligible patients must have received peginterferon alfa-2b (PEG-IFN alfa-2b) and ribavirin, but analyses evaluated only PEG-IFN alfa-2b use; BIC enrollees were matched with patients not enrolled in BIC (controls). Adherence was measured on the basis of the number of injections dispensed and the proportion of patients for whom an average of at least 1 injection per week was dispensed during follow-up. BIC subjects refilled 1.2 more injections than did controls (P < .001) within 12 weeks, 2.7 more (P < .001) within 24 weeks, and 6.7 more (P < .001) within 48 weeks. BIC enrollees were more likely than controls to refill the indicated dose (1 injection per week) within 12 weeks (72% vs 64%, P < .001), 24 weeks (52% vs 41%, P < .001), and 48 weeks (22% vs 13%, P = .002) of initiation. These data suggest that the BIC program may significantly improve adherence to PEG-IFN alfa-2b.

Predictors of discontinuing overactive bladder medications.

OBJECTIVE: To identify predictors of self-reported discontinuation of overactive bladder (OAB) medication using a three-phase survey. PATIENTS AND METHODS: In January 2005, a phase 1 survey was sent to 260 000 households in the USA to assess the prevalence of OAB symptom bother, treatment patterns and healthcare consulting behaviour. In July 2005, a detailed phase 2 follow-up survey was sent to 6577 phase 1 respondents who had used one or more OAB medications within the 12 months before phase 1; the phase 2 survey included questions about respondents' sociodemographic characteristics, general health status, OAB symptom bother, healthcare consulting behaviour, beliefs about OAB and treatment options, and medication usage. Six months later, a phase 3 survey was sent to 3387 phase-2 respondents who were persistent with OAB medication or had discontinued within <18 months of phase 2; the phase 3 survey measured the same variables as phase 2. Only phase 3 respondents who were persistent with OAB medication at phase 2 were included in the analyses reported here. Assessed were the proportions of respondents who were still persistent with OAB medication at phase 3 and who discontinued OAB medication between phases 2 and 3. The variables measured during the phase 2 survey were screened as potential predictors of discontinuation at phase 3 using univariate analysis and then assessed using multivariate logistic regression. RESULTS: Among 2838 respondents at phase 3 (84% response rate), 1194 had recently discontinued and 1644 were persistent with medication at phase 2. Among phase-3 respondents who were persistent at phase 2, 1040 (66%) continued to be persistent at phase 3, 280 (18%) had discontinued between phases 2 and 3, and 261 (17%) had switched medication between phases 2 and 3; 63 respondents had missing prescription information at phase 3. Predictors of discontinuing at phase 3 included smoking (odds ratio 1.80; 95% confidence interval 1.15-2.83; P = 0.010), not knowing whether treating bladder problems requires multiple daily doses of medication (1.71, 1.10-2.67; P = 0.018), believing (2.11, 1.34-3.33; P = 0.001) or not knowing (1.76, 1.23-2.52; P = 0.002) whether adverse effects of OAB medications are often severe, and being bothered 'quite a bit or more' by a sudden urge to urinate (1.54, 1.05-2.26; P = 0.028). Respondents taking two or more medications were less likely to discontinue (odds ratio 0.45-0.58; P < 0.05). CONCLUSION: Persistence with OAB medications might be improved by addressing predictors of discontinuation in the management of OAB, by proactively informing patients about the severity of antimuscarinic adverse effects, and dosing regimens. Bother associated with the key OAB symptom, urgency, is a predictor of discontinuation of treatment.

Patient-reported reasons for discontinuing overactive bladder medication.

OBJECTIVE: To evaluate patient-reported reasons for discontinuing antimuscarinic prescription medications for overactive bladder (OAB). PATIENTS AND METHODS: A phase 1 screening survey was sent to a representative sample of 260 000 households in the USA to identify patients using antimuscarinic agents for OAB. A detailed phase-2 follow-up survey was sent to 6577 respondents with one or more antimuscarinic prescriptions for OAB in the 12 months before the phase 1 survey. The follow-up survey included questions about demographics, clinical characteristics, antimuscarinic use, beliefs about OAB, treatment expectations, OAB symptom bother, and pre-coded reasons for discontinuation. Patients who reported discontinuing one or more OAB medication during the 12 months before phase 2 were grouped by reason, using latent class analysis (LCA); the Lo-Mendell-Rubin likelihood statistical test was used to determine the number of classes. Conditional probabilities of reasons for discontinuation were calculated for each class. Multivariable logistic regression was used to assess the influence of demographic and clinical characteristics on class assignment. RESULTS: In all, 162 906 (63%) and 5392 (82%) useable responses were returned in phases 1 and 2, respectively; the demographics were similar in respondents and nonrespondents in both phases. In all, 1322 phase 2 respondents (24.5%) reported discontinuing one or more antimuscarinic drugs during the 12 months before phase 2. LCA identified two classes (Lo-Mendell-Rubin statistic, P = 0.01) based on reasons for discontinuation. Most respondents (89%) reported discontinuing OAB medication primarily due to unmet treatment expectations and/or tolerability; many respondents in this class switched to a new antimuscarinic agent. A smaller group (11%) indicated a general aversion to taking medication. Age, sex, race, income, and history of incontinence were not predictive of class assignment. CONCLUSIONS: Expectations about treatment efficacy and side-effects are the most important considerations in discontinuing OAB medications for most patients. Interventions to promote realistic expectations about treatment efficacy and side-effects might enhance adherence.

Comparing adherence and persistence across 6 chronic medication classes.

BACKGROUND: The National Quality Forum recently endorsed the proportion of days covered (PDC)-a measure of medication adherence-as an indicator of quality in drug therapy management. OBJECTIVE: To inform initial efforts to improve the quality of drug therapy management, we compared PDC and persistence among new users of 6 commonly used chronic medication categories. METHODS: A retrospective analysis of pharmacy claims in a database of more than 64 million members enrolled in 100 health plans assessed persistence and adherence to drug therapy in 6 chronic conditions. Patients were included in the analysis if they initiated a prescription drug of interest in any of 6 drug classes-prostaglandin analogs, statins, bisphosphonates, oral antidiabetics, angiotensin II receptor blockers (ARBs), and overactive bladder (OAB) medications-between January 1 and December 31, 2005. The first claim for a drug of interest during this period was considered a patient's index date. Patients were required to have a minimum of 12 months of continuous enrollment both preceding and following their index date. New users of a treatment were identified by excluding patients who filled a prescription for any drug in the same class during the previous 12 months and were followed for a minimum of 12 months. Nonpersistence was defined as discontinuation of the therapy class following an allowed gap between refills-30-, 60-, and 90-day refill gaps were used. Adherence was defined as a continuous measure of the proportion of days covered (PDC) during the 12-month post-index period. Logistic regression analyses predicted (a) nonpersistence during the 12-month post-index period and (b) adherence (PDC) of at least 80%, with drug class as the predictor variable of interest, controlling for demographic variables, insurance and plan type, history of hospitalization, Charlson comorbidity score, copayment for index medication, and number of medications at index. RESULTS: A total of 167,907 patients were identified across 6 cohorts. Using the 60-day gap, 6-month persistence rates were prostaglandin analogs 47%, statins 56%, bisphosphonates 56%, oral antidiabetics 66%, ARBs 63%, and OAB medications 28%. After the first 90 days of therapy, relative persistence was stable across cohorts, and rates declined consistently from 6 months post-index to study end. Logistic regression models showed that oral antidiabetic users had a 59%, 36%, 37%, and 79% decreased risk of nonpersistence in a 12-month follow-up period compared with patients taking prostaglandin analogs, statins, bisphosphonates, or OAB medications, respectively. Risk of nonpersistence decreased with increasing age. Mean (SD) 12-month adherence rates were: prostaglandin analogs 37% (26%), statins 61% (33%), bisphosphonates 60% (34%), oral antidiabetics 72% (32%), ARBs 66% (32%), and OAB medications 35% (32%). Logistic regression indicated that oral antidiabetic use was a significant predictor of adherence (PDC) of at least 80% compared with other therapy classes. Adjusted odds ratios for oral antidiabetics were 17.60 (95% confidence interval [CI] = 15.38-20.14) versus prostaglandin analogs, 2.06 (95% CI = 1.99-2.12) versus statins, 1.92 (95% CI = 1.83-2.02) versus bisphosphonates, 1.29 (95% CI = 1.24-1.34) versus ARBs, and 5.77 (95% CI = 5.38-6.19) versus OAB medications. CONCLUSION: This analysis of adherence (PDC) and persistence across a sample of 6 chronic therapies found variable but uniformly suboptimal medication use. Adherence to prostaglandin eye drops and OAB medications was lower than to cardiovascular, oral antidiabetic, and oral osteoporosis therapies. These findings provide useful baseline information for the development of initiatives to improve the quality of drug therapy management.

Difficult to swallow: patient preferences for alternative valproate pharmaceutical formulations.

OBJECTIVE: To determine the degree to which swallowing valproate (VP) tablets is an issue, the proportion of patients who would prefer an alternative formulation, and the predictors of preference. METHODS: A quantitative telephone survey of eligible adults (n = 400, >/=18 years old) who currently take (n = 236) or previously took (n = 164) VP tablets within the past 6 months was conducted. RESULTS: More than half of the patients indicated that VP tablets were 'uncomfortable to swallow' (68.5%, n = 274) and were 'very interested' (65.8%, n = 263) in medications that were easier to swallow. When choosing conceptually between taking VP tablet once/day or an equally safe and effective but significantly smaller soft gel capsule twice per day, the 82.8%, (n = 331) preferred the soft gel capsule. In the multivariate regression analysis, perceiving soft gel capsules to be easier to swallow (OR = 73.54; 95% CI = 15.01 to 360.40) and taking VP more frequently (OR = 2.02; 95% CI = 1.13 to 3.61) were significant predictors of soft gel capsule treatment preference. CONCLUSION: VP users would prefer a formulation that is easier to swallow, even if it is needed to be taken twice per day. When choosing between medications with similar efficacy and safety, physicians can consider patient preferences to optimize conditions for medication adherence.

Are high-risk hypertensive patients being prescribed concomitant statin therapy?: a retrospective cohort study.

BACKGROUND: Treatment guidelines for dyslipidemic patients have focused on lipid levels and risk assessments. However, normolipidemic patients who have multiple risk factors for cardiovascular disease may also benefit from HMG-CoA reductase inhibitor (statin) therapy. OBJECTIVE: We examined the frequency of statin prescriptions in patients initiating antihypertensive drug treatment in a US managed-care setting. STUDY DESIGN AND PATIENT: This retrospective cohort study used the PharMetrics' Patient-Centric Database to identify enrollees initiating antihypertensive treatment (September 2001 to February 2004). Patients newly treated with antihypertensives and with various levels of coronary heart disease (CHD) risk (including dyslipidemia, established CHD, type 2 diabetes mellitus, and no CHD but three or more cardiovascular risk factors) were included in the study. MAIN OUTCOME MEASURE: Cumulative probability of receiving statin therapy each month after antihypertensive initiation. Multivariable logistic regression was used to identify factors associated with receiving concomitant statin therapy. RESULTS: Of 142 389 patients (mean age 51.7 years) newly treated with antihypertensives, 32 056 (22.5%) were prescribed statins within 1 year. The cumulative probability of being prescribed a statin increased with increasing numbers of CHD risk factors, irrespective of dyslipidemia status. After adjusting for age, sex, and other potential predictors, patients were more likely to receive statin therapy if they had a history of dyslipidemia (adjusted odds ratio [AOR] 5.68 [95% CI 5.52, 5.85]), established CHD/congestive heart failure (AOR 3.39 [95% CI 3.16, 3.63]), or three or more additional cardiovascular risk factors but no CHD (AOR 3.01 [95% CI 2.74, 3.30]). CONCLUSION: Among patients beginning antihypertensive treatment, those with established CHD or CHD risk factors were more likely to receive statins, but a substantial fraction did not fill any statin prescription. The increased use of statin therapy could benefit many hypertensive patients with additional CHD risk factors.

Association between prescription burden and medication adherence in patients initiating antihypertensive and lipid-lowering therapy.

PURPOSE: The association between prescription burden and medication adherence in patients initiating antihypertensive and lipid-lowering therapy was studied. METHODS: Patients enrolled in managed care organizations who initiated antihypertensive therapy coincident with lipid-lowering therapy (no more than 90 days apart) between January 1, 1997, and April 30, 2000, were eligible for inclusion. Analysis was limited to new users of antihypertensive and lipid-lowering therapy. The proportion of days covered (PDC) by antihypertensive and lipid-lowering therapy was calculated for the first year after therapy initiation; patients with a PDC of > or =80% for both drug classes were considered adherent. Prescription burden was defined as the number of prescription medications taken in the year prior to starting antihypertensive and lipid-lowering therapy. Demographic, clinical, and health-service-use variables associated with both prescription burden and medication adherence were measured using medical and pharmacy claims data from the year before initiation of antihypertensive and lipid-lowering therapy. RESULTS: Among 5759 patients, the mean +/- S.D. prescription burden was 3.6 +/- 3.7 (median, 3) medications, and the mean +/- S.D. PDC with antihypertensive and lipid-lowering therapy was 53.9% +/- 31.9% (median, 58.5%). Among patients with 0, 1, and 2 prior medications, 41%, 35%, and 30% of patients were adherent, respectively, to antihypertensive and lipid-lowering therapy. Among patients with 10 or more prior medications, 20% were adherent. CONCLUSION: Among patients in a managed care database taking antihypertensive and lipid-lowering medications, adherence to those regimens became less likely as the number of prescription medications increased. The reduction in adherence with additional prescription medications was greatest in patients with the fewest preexisting prescriptions.

Generic and therapeutic statin switches and disruptions in therapy.

BACKGROUND: The study objective was to compare dose-equivalence, adherence and subsequent switch rates among patients recently switched from a branded to generic version of the same statin (generic substitution, GS) vs. those switched from branded statin to generic version of a different statin (therapeutic substitution, TS). METHODS: In a retrospective cohort analysis among adult enrollees in over 90 US health plans, the authors identified adult patients who switched from a branded to generic statin from July-December 2006 (simvastatin became generic in June 2006). Patients were classified by type of statin switch: GS (e.g., branded simvastatin --> generic simvastatin), and TS (e.g., branded atorvastatin --> generic simvastatin). Demographic and clinical data were collected from claims before switch through 6 months follow-up. Separate outcomes of interest included proportion of patients that switched to a less potent daily dose, that switched back to previous branded statin after switch, and that were at least 80% adherent during the 6 months after initial switch. Significant predictors of each clinical outcome were identified using multivariable logistic regression models, adjusting for differences between groups in covariates and potential confounders. RESULTS: The 6-month TS (n = 3807) and GS (n = 40,165) groups were generally similar demographically. Compared to GS, TS patients were significantly more likely to be switched to a less potent dose (26.2% vs. 0.5%, adjusted odds ratio [AOR] in patients with high-potency index medication = 83.4, p < 0.0001); 33% less likely to be adherent in the 6 months after switch (67.7% vs. 75.9%, AOR in patients with no switch in first 6 months follow-up = 0.67, p < 0.0001); and four times more likely to switch back to previous branded statin (11.3% vs. 2.9%, AOR = 4.1, p < 0.0001). LIMITATIONS: This study did not account for co-payment changes, lipid measurements, or changes in pill burden. CONCLUSIONS: While this study did not have data on why patients had TS (e.g., for cost or clinical reasons), TS was more likely to involve a subsequent disruption to statin therapy than GS. TS could potentially lead to adverse impacts on patients' outcomes, and should be studied further.

Bother related to bladder control and health care seeking behavior in adults in the United States.

PURPOSE: We measured patient reported bother due to overactive bladder syndrome, patterns of physician consultation and prescription medication use for overactive bladder symptoms in adults in the United States. MATERIALS AND METHODS: A survey sample was derived from a consumer panel of 600,000 American households developed to match the United States Census of 260,000 adults. The survey included the Overactive Bladder-Validated 8 awareness tool, which includes 8 questions that measure the degree of bother due to specific bladder symptoms. A score of 8 or greater denotes probable overactive bladder. Additional questions probed treatment patterns, health care consultation, overactive bladder diagnosis, treatment type and prescription treatment used. A nonrespondent telephone survey in 1,004 participants was done to evaluate differences between mail survey respondents and nonrespondents. RESULTS: The response rate was 63% (162,906 respondents). Women represented 55.1% of the sample and 21.8% of respondents were 65 years old or older. Symptom bother, as determined by an Overactive Bladder-Validated 8 score of 8 or greater, was reported by 26.6% of the total sample, including 23.7% of men and 28.9% of women. The percent of men and women reporting bother increased with age. Of respondents with probable overactive bladder only 45.7% had discussed the symptoms with a medical provider, 22.5% had previously used prescription medication for overactive bladder, 13.5% had used overactive bladder medication in the last 12 months and 8.1% were currently on treatment. CONCLUSIONS: A substantial proportion of adults in the United States reported some degree of bother due to overactive bladder symptoms. The degree of bother was associated with age and gender. Overall less than half of patients with probable overactive bladder discussed the symptoms with a health care provider. A small proportion was prescribed medication and an even smaller proportion was currently on treatment.