0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

National Trends in Cyclooxygenase-2 Inhibitor Use Since Market Release:  Nonselective Diffusion of a Selectively Cost-effective Innovation FREE

Carolanne Dai, BSc, MSc; Randall S. Stafford, MD, PhD; G. Caleb Alexander, MD, MS
[+] Author Affiliations

Author Affiliations: Harris School of Public Policy Studies (Ms Dai) and the Robert Wood Johnson Clinical Scholars Program and MacLean Center for Clinical Medical Ethics (Dr Alexander), The University of Chicago, Chicago, Ill; Stanford Prevention Research Center, Stanford University, Stanford, Calif (Dr Stafford); and the Department of Internal Medicine, University of Chicago Hospitals, Chicago (Dr Alexander).


Arch Intern Med. 2005;165(2):171-177. doi:10.1001/archinte.165.2.171.
Text Size: A A A
Published online

Background  The withdrawal of rofecoxib has highlighted concerns regarding the safety of cyclooxygenase-2 (COX-2) inhibitors. In some patients COX-2 inhibitors may be safer than nonselective nonsteroidal anti-inflammatory drugs (NSAIDs); however, the public health benefit of COX-2 inhibitors depends on their use in patients at higher than normal risk from NSAIDs. We examined trends in COX-2 inhibitor use based on risk for adverse events from NSAIDs.

Methods  We analyzed data from the National Ambulatory Medical Care Survey (1999-2002) and National Hospital Ambulatory Medical Care Survey (1999-2001), nationally representative surveys of community and hospital-based outpatient practices. The main outcome measure was the proportion of patient visits in which COX-2 inhibitors were prescribed, stratified by risk of adverse gastrointestinal (GI) events from NSAIDs.

Results  Of the visits in which either a COX-2 inhibitor or NSAID was prescribed, the frequency of COX-2 inhibitor use increased from 35% (1999) to 55% (2000) to 61% (2001 and 2002). Among patients with the lowest risk for adverse events from NSAIDs, the proportion receiving a COX-2 inhibitor increased from 12% in 1999 to 35% in 2002. Overall, increases in COX-2 inhibitor use among patients in whom NSAIDs could be used accounted for more than 63% of the growth in COX-2 inhibitor use during the period examined.

Conclusions  Marked increases in COX-2 inhibitor use have occurred since their release, primarily among patients at low risk for adverse events from NSAIDs. These findings demonstrate the challenge of limiting innovative therapies to the settings in which they are initially targeted and maximally beneficial.

Figures in this Article

The clinicians’ choice between cyclooxygenase-2 (COX-2) inhibitors and traditional nonsteroidal anti-inflammatory drugs (NSAIDs) has always been complex. Clinical trials among select populations have demonstrated that COX-2 inhibitors have the same efficacy as NSAIDs but have less gastrointestinal (GI) adverse effects.13 However, the shorter experience with COX-2 inhibitors has led to uncertainty regarding their possible adverse effects,3 which was highlighted by the recent withdrawal of rofecoxib from the market in September 2004. Furthermore, the choice of a COX-2 inhibitor in any patient has always come at considerable expense, since the wholesale price of COX-2 inhibitors is markedly greater than that of NSAIDs.4 Because most of the benefit of COX-2 inhibitors accrues to those at highest risk of NSAID-associated GI toxic effects,5 many guidelines have limited the use of COX-2 inhibitors to those at highest risk from NSAIDs.6,7

Regardless of the ultimate fate of this innovative pharmaceutical class, lessons regarding the evidence-based use of COX-2 inhibitors are particularly important given concerns regarding rising prescription costs. About 40% of these costs are attributable to the use of new drugs rather than changing patient demographics and an increase in the number of drugs per patient.8 Such costs are increasingly paid for out of pocket, pose a growing burden on millions of Americans, and challenge patients, clinicians, and policy makers alike. For individual patients and clinicians, the choice between a COX-2 inhibitor and an NSAID has represented a paradigmatic case of a cost/quality trade-off that may be an important yet neglected topic of discussion in clinical practice.9 At a policy level, trends in the use of innovative but costly pharmaceuticals have important implications for the long-term viability of initiatives such as the Medicare prescription drug benefit as well as efforts to control escalating prescription drug costs.

New technologies are not adopted homogenously among a population,10 and limiting new technologies to settings of maximally proven benefit are seldom successful.11 For example, one recently described study examined the “treatment-risk” paradox of statin use, whereby patients at highest risk of adverse cardiac events were least likely to be treated with these cholesterol-lowering agents.12 Such nonselective diffusion of technologies may undermine their cost-effectiveness depending on the degree of nonselective uptake and the marginal benefit among different populations of users.13

We sought to examine longitudinal trends in the use of COX-2 inhibitors with a focus on the selectivity of use in populations at highest risk for GI adverse events from NSAIDs. In addition to examining patient characteristics, we also explored nonclinical characteristics associated with COX-2 inhibitor use. Although several studies have examined how these characteristics influence the choice to use a COX-2 inhibitor,1418 these studies have generally been conducted among homogenously insured populations and included little detail about physician and visit characteristics that have been demonstrated to be associated with prescribing patterns in other settings.1921

DATA

We used data from the National Ambulatory Medical Care Survey22 (NAMCS, 1999-2002) and the National Hospital Ambulatory Medical Care Survey23 (NHAMCS, 1999-2001). Designed and conducted by the National Center for Health Statistics, Hyattsville, Md, NAMCS is a national probability sample of office-based physicians that provides data on patient office visits. It uses a 3-stage probability sampling procedure that has been previously described.22 The survey uses a 1-page data form completed by the physician or office staff that includes information about patient, physician, and visit characteristics. For each office visit, physicians are asked to record up to 6 prescription or over-the-counter medications for which therapy is either being continued or prescribed. The counterpart of NAMCS, NHAMCS, is a similar national probability sample that uses a 4-stage design to sample visits to outpatient departments of noninstitutional general and short-stay hospitals.23 Patient visit weights in both surveys are adjusted to account for nonresponse and nonparticipation.

GI RISK ASSESSMENT TOOL

Similar to the method of Doshi et al,24 we used a modified version of the GI score risk assessment tool25 to quantify each patient’s risks for NSAID-induced GI adverse events. The GI risk assessment tool is an instrument that weighs 6 items (subject’s age, self-reported health, history of rheumatoid arthritis, corticosteroid use, GI bleeding or ulcers, and GI symptoms with NSAID use) to stratify patients into 4 levels of risk from traditional NSAIDs.26 Based on the method of Doshi et al,24 we included the use of anticoagulants and antiplatelets as additional risk factors. According to this method of risk stratification, subjects with “very low risk” or “low risk” are recommended to receive NSAIDs, subjects with “moderate risk” are recommended to receive different medicines based on the length of expected treatment, and subjects with “high risk” are recommended to receive COX-2 inhibitors. Because we did not have information on self-reported health or length of corticosteroid use in our cross-sectional data, we assumed that subjects were in “fair” health (2 on a 0-4 scale) and that any corticosteroid use was for a moderate duration (3 on 0-5 scale). In our analyses of trends in COX-2 inhibitor use based on the risk of adverse events from NSAIDs, we conducted several sensitivity analyses varying the self-reported health of the population, the duration of corticosteroid use, and the inclusion of antiplatelets and anticoagulants in the GI risk score. We also examined the effect of dichotomizing all patients based on the presence of at least 1 main risk factor for adverse events from NSAIDs (eg, age >65 years) as well as limiting our analyses to patients younger than 65 years who were not receiving anticoagulants.

STATISTICAL ANALYSIS

Because the first COX-2 inhibitors (celecoxib) were released in January 1999, we used descriptive statistics, applying patient sampling weights, to examine trends in the use of COX-2 inhibitors (rofecoxib, celecoxib, and valdecoxib) and NSAIDs (ibuprofen, indomethacin, naproxen, diclofenac, etodolac, fluribiprofen, ketoprofen, ketorolac, meclofenamate, meloxicam, nabumetone, oxaprozin, piroxicam, sulindac, tolmetin) from 1999 through 2002. To examine predictors of COX-2 inhibitor use, we defined our outcome variable as the choice between a COX-2 inhibitor and an NSAID, conditional on having received 1 of these 2 medication classes. We excluded the 0.4% of patients with prescriptions for both an NSAID and a COX-2 inhibitor. We used χ2 analyses to evaluate the bivariate association between hypothesized characteristics of patients (age, sex, race, comorbid conditions, and GI risk score), physicians (specialty and employment status), and visits (source of payment, region of country, new vs established patient, year, type of office, owner of practice, and solo vs group practice) and the outcome of interest. We performed weighted logistic regression for complex survey data to examine the multivariate association between the predictor variables and our outcome variable.27 Initial models included basic demographic characteristics of patient visits, variables significant on bivariate analysis (P<.25), and an interaction term between year and GI risk score to assess whether the association between GI risk and the likelihood of COX-2 inhibitor receipt was independently modified by the year of observation. We also examined several other interaction terms that we hypothesized a priori might be important explanatory variables (eg, race interacted with source of payment, physician specialty interacted with time spent with physician, and physician specialty interacted with patient GI risk), but they did not add considerably to the model’s goodness of fit. Because most comorbid conditions were present in fewer than 5% of all patient visits, we aggregated these comorbid conditions into 2 categories—those that might be an indication for COX-2 inhibitors rather than NSAIDs (GI bleeding, peptic ulcer disease, rheumatoid arthritis, corticosteroid use, coagulation defects, history of heartburn, stomach pain, nausea, or vomiting) and those that might be a relative contraindication for either COX-2 inhibitors or NSAIDs (congestive heart failure, liver dysfunction, or renal dysfunction). We refined our multivariate model using the Hosmer-Lemeshow goodness-of-fit test and the Pregibon Linktest for Nonlinearity. Our final models were robust, maximized goodness of fit, and included basic sociodemographic variables (eg, race) and variables that were statistically significant in the earlier models (P<.05). We examined the impact of omitting alternative analgesics (opioids, opioid analogues, and acetaminophen) from our analyses. There were no statistically significant trends in the use of these medicines from 1999 through 2002, nor was the use of these analgesics associated with GI risk score. Thus, we reasoned these alternatives were not important substitutes for COX-2 inhibitors or NSAIDs in our analyses. We also conducted sensitivity analyses that examined multivariate models limited to the elements of the GI risk score and that dichotomized patients based on the presence of any of the main risk factors for adverse events from NSAIDs (eg, age >65 years). All analyses were conducted using Stata statistical software (Stata Corporation, College Station, Tex).

PATIENT VISITS WITH COX-2 INHIBITOR OR NSAID USE

There were 4893 visits from 1999 through 2002 in which therapy with a COX-2 inhibitor or an NSAID was either continued or prescribed, corresponding to a national estimate of 221.8 million visits (95% confidence interval [CI], 208.8-238.1 million visits). Table 1 describes the characteristics of these visits. For example, the mean age of patients among all visits was 52 years, 63% of visits were made by women, 83% of visits were made by white patients, and 70% of visits took place in general medicine or family medicine practices. Among all visits, the risk for adverse events from NSAIDs varied, with 31% classified as “very low risk,” 42% as “low risk,” 25% as “moderate risk,” and 2% as “high risk.”

Table Graphic Jump LocationTable 1. Characteristics of Patient Visits With COX-2 Inhibitor or NSAID Use (1999-2002)*
TRENDS IN THE USE OF COX-2 INHIBITORS

Table 2 describes changes in the use of COX-2 inhibitors and NSAIDs over the period examined. Overall, the use of these medicines increased from 42.4 million (95% CI, 35.8-50.1 million visits) of 841.4 million visits (5.0%) in 1999 to 56.9 million (95% CI, 50.6-63.9 million visits) of 890.0 million visits (6.4%) in 2002. Of the visits in which 1 of these 2 drug classes was used, the proportion in which a COX-2 inhibitor was used increased from 35% (1999) to 55% (2000) to 61% (2001 and 2002). This corresponds with a mean increased rate of use of 23% per year, taking into account the 0% change between the years 2001 and 2002.

Table Graphic Jump LocationTable 2. National Visit Estimates With COX-2 Inhibitor or NSAID Use (1999-2002)*

The Figure depicts changes in the types of patient visits in which COX-2 inhibitors were prescribed stratified by risk of adverse GI events. Among patient visits with the lowest risk of GI toxic effects, in 1999, 12% had a COX-2 inhibitor prescription, and this proportion increased to 40% in 2000 and to 37% in 2001. By comparison, the proportion of patient visits with the highest risk of GI toxic effects and a COX-2 inhibitor prescription ranged from 54% to 98% over the same period.

Place holder to copy figure label and caption
Figure.

Cyclooxygenase-2 inhibitor use stratified by risk of adverse events from nonsteroidal anti-inflammatory drugs (1999-2002).

Graphic Jump Location
COX-2 INHIBITOR USE STRATIFIED BY GI RISK

Table 3 depicts changes in the frequency of COX-2 inhibitor use stratified by risk of GI adverse events. For example, among patient visits with a very low risk, the number in which a COX-2 inhibitor was used increased from 1.7 million (95% CI, 1.0-2.7 million) in 1999 to 6.1 million (95% CI, 4.6-7.8 million) in 2002. This increase accounts for 22.4% of the growth in COX-2 inhibitor use over this period:              (6.1 Million – 1.7 Million)/(34.6 Million – 15.0 Million).

Table Graphic Jump LocationTable 3. Use of COX-2 Inhibitors Stratified by Risk of Adverse GI Events From NSAIDs (1999-2002)*

Our findings from the sensitivity analyses yielded similar patterns of diffusion of COX-2 inhibitors over the period examined. For example, increases in use of COX-2 inhibitors among patient visits over the years examined stratified by very low, low, moderate, and high GI risk ranged from 22.4% to 46.9% (among visits with very low GI risk), 20.9% to 40.8% (among low-risk visits), 16.8% to 46.4% (among moderate-risk visits), and 0.0% to 12.2% (among high-risk visits). Thus, all models indicated that over time growth in COX-2 inhibitor use occurred primarily among visits with lower GI risk, although the magnitude of this shift depended on the specific assumptions of the model. We also examined the potential for underuse of COX-2 inhibitors among patient visits based on risk of adverse GI events from NSAIDs. Rates of NSAID use among visits with moderate or high risk from this drug class using the GI risk tool ranged from 9% to 16% (among visits with moderate risk) and 0% to 2% (among visits with high risk).

Table 4 depicts trends in COX-2 inhibitor use among patient visits in which a relative contraindication to both COX-2 inhibitors and NSAIDs was reported (eg, congestive heart failure). Among these visits, in 1999, approximately 2.9 million visits were associated with COX-2 inhibitor use and 3.7 million visits with NSAID use. By 2002, the number of patient visits associated with COX-2 inhibitor use increased more than 5-fold by 2002 (16.6 million) whereas the number of visits associated with NSAID use decreased somewhat (2.2 million).

Table Graphic Jump LocationTable 4. National Visit Estimates With COX-2 Inhibitor or NSAID Use Among Patients With Congestive Heart Failure, Liver Dysfunction, or Renal Dysfunction (1999-2002)*
CHARACTERISTICS ASSOCIATED WITH RECEIPT OF A COX-2 INHIBITOR

On multivariate analysis, only a few characteristics were independently associated with COX-2 inhibitor use (Table 5). For example, female visits were more likely to include receipt of a COX-2 inhibitor than were male visits (odds ratio [OR], 1.44; 95% CI, 1.19-1.74), patient visits to surgical specialists were more likely to be associated with COX-2 inhibitor use than those to general internists (OR, 1.39; 95% CI, 1.02-1.94), and patient visits that took place in a physician-owned practice were more likely to receive a COX-2 inhibitor than those in a health maintenance organization or hospital-owned setting (OR, 2.32; 95% CI, 1.63-3.30). In our models, GI risk score was associated with COX-2 inhibitor use, and this effect was modified by the year examined, as indicated by the statistically significant interaction term between GI risk score and year.

Table Graphic Jump LocationTable 5. Association Between Patient, Physician, and Visit Characteristics and COX-2 Inhibitor Use (1999-2002)*

Although we found higher rates of COX-2 inhibitor use among some physicians, the selectivity of use based on GI risk did not differ markedly based on physician specialty or practice type. For example, analyses limited to patient visits in physician-owned practices showed that from 1999 through 2002, 11% to 24% of COX-2 inhibitors were prescribed in visits with very low risk of adverse events from NSAIDs, while 42% to 45% of COX-2 inhibitors were prescribed in visits with low risk of these events.

Sensitivity analyses limited to the elements of the GI risk score continued to show statistically significant (P<.05) increases in the use of COX-2 inhibitors over time (ORs, 1.40-1.44 per additional year) and greater COX-2 inhibitor use among patient visits in physician-owned practices (ORs, 2.38-2.39), although associations between greater COX-2 inhibitor use and visits involving surgical subspecialists varied slightly based on the assumptions of the model (OR, 1.35 [95% CI, 0.98-1.86] for models with patient visits dichotomized into groups based on the presence of any risk factor; OR, 1.39 [95% CI, 1.00-1.93] for models limited to elements of the GI risk score).

To our knowledge, this is the first study to examine the longitudinal pattern of diffusion of COX-2 inhibitors after market release with a focus on the characteristics of those receiving the drug. This examination took place among a broad sample of patient visits in which detailed patient, physician, and visit characteristics were available. We found considerable increases in COX-2 inhibitor use occurring among patients at the lowest risk for GI toxic effects from NSAIDs. We also found that several nonclinical factors were as important as established patient risk factors for NSAID-related GI toxic effects in determining COX-2 inhibitor use.

There are several possible reasons for these trends. Diffusion of new technologies is seldom smooth or uniformly achieved selectively among the population that stands to gain the most from the technology.10 Our results demonstrate how the phenomenon of “therapeutic creep,” which has been described in relation to the adoption of unproven surgical techniques such as carotid endarterectomy28 and cholecystectomy,29 is applicable to the diffusion of pharmaceuticals. This may be in part because of the tendency to equate “newer” with “better” medicines30 and because of the powerful impact that brand loyalty can have on prescribing behavior.31 In addition, the impact of marketing and promotional efforts must also be considered. COX-2 inhibitors have been heavily promoted, both through direct-to-consumer advertising as well as to physicians. For example, in 2000, Vioxx (rofecoxib; Merck and Co Inc, Whitehouse Station, NJ) was the most heavily advertised direct-to-consumer drug with expenditures of $161 million.32 Given that perceptions of innovations are strong predictors of rates of spread,10 aggressive marketing techniques to patients and physicians may help to explain the observed growth in COX-2 inhibitor use. Our findings that the growth in COX-2 inhibitor use has exceeded the decrease in the use of NSAIDs suggest that COX-2 inhibitors have not only eroded NSAID market share but have also increased total market demand. This finding is consistent with studies suggesting that direct-to-consumer advertising may increase market share for classes of drugs.33 Also, independent of advertising effects, increased product variety may facilitate better matches between heterogeneous patient preferences and treatments and thereby increase market size.34

For patients and physicians, our findings raise the concern that the marginal benefit of COX-2 inhibitor use may be increasingly small, considering the growing tendency for their nonselective use in populations that are not at high risk for adverse events from NSAIDs. The market withdrawal of rofecoxib has highlighted the importance of physicians and patients carefully considering the relative risks and benefits of COX-2 inhibitors compared with alternative analgesics. Such considerations should include the new knowledge regarding the risk of cardiovascular events from rofecoxib, as well as the findings that concomitant use of aspirin with COX-2 inhibitors may diminish the selective safety advantage of COX-2 inhibitors among high-risk patients.1 Our results support the findings of a cross-sectional study that identified suboptimal cost-effective use of COX-2 inhibitors.35 Although the actual out-of-pocket costs of COX-2 inhibitors varies, their mean cost is considerably greater than that of NSAIDs4 and may further burden patients already struggling to afford escalating prescription costs.9 These and other findings36 indicate that patients should be encouraged to discuss their prescription costs with their physician and increasingly participate in the numerous cost-quality trade-offs often inherent in prescription choice. Such enhanced communication about costs may help to potentiate the cost-effectiveness of tiered formularies, reference-based pricing, and other innovative methods of pharmaceutical regulation.

For policy makers, these results demonstrate that the increasing nonselective use of COX-2 inhibitors among visits with patients who are not at high risk from NSAID-related adverse events threatens their overall cost-effectiveness in actual practice. There is no doubt that, based on currently available evidence, some fraction of patients will benefit from COX-2 inhibitors on the basis of relative contraindications to nonselective NSAIDs. While it may be difficult to estimate this fraction, it is likely to be far lower than the 61% of patient visits with receipt of a COX-2 inhibitor rather than NSAID in 2001 and 2002. Similar to the treatment-risk paradox,12 the tendency toward increasing nonselective use of a marginally much more costly treatment dramatically reduces the aggregate benefit of the technology.13 Cost-effective analyses of COX-2 inhibitor use have been sensitive to the risk for adverse GI events among the target population.37,38 Our results reinforce the importance, when evaluating prospective analyses of innovative therapies, of considering the degree of nonselective uptake that is likely to take place and how this may change over time.39,40

Such policy considerations are especially important in the aftermath of the removal of rofecoxib from the market. The nonselective use of COX-2 inhibitors that we identify led to an unnecessarily large population of patients being exposed to a hitherto not well-characterized cardiovascular risk. As illustrated by the examples of fenfluramine-phentermine (fen-phen) and troglitazone, overall harm from a new pharmaceutical may be increased when rapid expansion of prescribing occurs prior to the development of definitive data on safety. With new drugs whose safety profile is not well characterized, greater regulatory efforts to limit the use of the drug to the clinical population in which an unambiguous outcome benefit exists may minimize the potential for overall public harm.

In addition to the nonclinical patient characteristics that we examined, we also found that visits with physicians in surgical subspecialties and physician-owned practices were more likely to include receipt of a COX-2 inhibitor than were visits with physicians in general medicine or hospital/health maintenance practices, respectively. This variation in practice patterns may be in part due to differences in patient case-mix. Patients who have had prior trials of multiple NSAIDs may be more likely to see a specialist and receive a COX-2 inhibitor prescription. In addition, our findings may be due to differences in the dissemination of information about new medical technologies. Specialists, and perhaps physicians in physician-owned practices, have greater exposure to pharmaceutical detailing of newer drugs than do general practitioners and are quicker to adopt new treatments.4144 Despite these associations, we did not find large differences in the selectivity of COX-2 inhibitor use based on physician specialty or practice ownership.

This study has several limitations. First, NAMCS and NHAMCS measure office visits rather than individual patients and therefore oversample frequent users of medical care, do not sample visits outside of office-based settings, and do not provide information on treatment outcomes. Second, this analysis is limited to prescribed or over-the-counter medications recommended by physicians and thus does not include over-the-counter medicines that patients use without their physicians’ knowledge. Third, our cross-sectional data do not allow for us to examine the frequency of drug switches (eg, from NSAIDs to COX-2 inhibitors), systematic trends in the undercoding of variables such as comorbid conditions, or the effect of advertising and promotional efforts on prescription choice. Fourth, alternative methods of stratifying patients by GI risk from NSAIDs could yield different conclusions regarding the selectivity of COX-2 inhibitor use. However, the sensitivity analyses we conducted support our findings of large increases in COX-2 inhibitor use among those at lowest risk for adverse events from NSAIDs. Finally, since we do not have 2002 data for NHAMCS, we may have underestimated or overestimated the true rate of change of COX-2 inhibitor use from 2001 to 2002. However, analysis stratified by data source from 1999 through 2001 suggest similar trends in the growth of COX-2 inhibitor use over this period.

Our study demonstrates a marked change in the types of patient visits in which COX-2 inhibitors are prescribed since their release in 1998. The evidence that visits with the lowest risk of adverse events from traditional NSAIDs are increasingly including the receipt of their considerably more expensive counterparts jeopardizes the cost-effectiveness of COX-2 inhibitors and may be applicable to the adoption of other innovative therapies such as newer antihypertensives (eg, angiotensin 2 receptor blockers) and antiplatelet agents (eg, adenosine diphosphate receptor blockers). Efforts to focus COX-2 inhibitor use to settings of clear clinical benefit offers one means of reducing prescription drug expenditures without compromising the quality of patient care.

Correspondence: G. Caleb Alexander, MD, MS, The University of Chicago, 5841 S Maryland, MC 2007, Chicago, IL 60637 (galexand@uchicago.edu).

Accepted for Publication: November 16, 2004.

Financial Disclosure: None.

Funding/Support: Dr Alexander was supported by the MacLean Center for Clinical Medical Ethics, Chicago, Ill, and a Geriatric Academic Program Award (K12AG00488) from the National Institute on Aging, Bethesda, Md, to the University of Chicago. Dr Stafford was supported by grant RO1-HS11313 from the Agency for Healthcare Research and Quality, Rockville, Md. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

Acknowledgment: We gratefully acknowledge Will Manning, PhD, for helpful contributions to the study design, analyses, and interpretation.

Silverstein  FEFaich  GGoldstein  JL  et al.  Gastrointestinal toxicity with celecoxib vs. nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. JAMA 2000;2841247- 1255
PubMed Link to Article
Bombardier  CLaine  LReicin  A  et al. VIGOR Study Group, Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med 2000;3431520- 1528
PubMed Link to Article
Mukherjee  DNissen  SETopol  EJ Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 2001;286954- 959
PubMed Link to Article
 Drug Topics Redbook 2003.  Montvale, NJ Medical Economics Co2003;
Marshall  JKPellissier  JMAttard  CLKong  SXMarentette  MA Cost-effectiveness analysis comparing rofecoxib with nonselective NSAIDs in osteoarthritis. Pharmacoeconomics 2001;191039- 1049
PubMed Link to Article
American Academy of Orthopaedic Surgeons, AAOS Clinical Practice Guideline on Osteoarthritis of the Knee.  Rosemont, Ill American Academy of Orthopaedic Surgeons2003;17
National Institute for Clinical Excellence, Guidance on the Use of Cyclo-oxygenase (Cox) II Selective Inhibitors, Celecoxib, Rofecoxib, Meloxicam, and Etodolac for Osteoarthritis and Rheumatoid Arthritis.  London, England National Institute for Clinical Excellence2001;1- 14Technology Appraised Guidance No. 27
The National Institute for Health Care Management Research and Education Foundation, Factors Affecting the Growth of Prescription Drug Expenditures.  Washington, DC The National Institute for Health Care Management Research and Education Foundation July9 1999;
Alexander  GCCasalino  LPMeltzer  DO Patient-physician communication about out-of-pocket costs. JAMA 2003;290953- 958
PubMed Link to Article
Berwick  DM Disseminating innovations in health care. JAMA 2003;2891969- 1975
PubMed Link to Article
 Institute of Medicine Committee on Health Care in America. Crossing the Quality Chasm A New Health System for the 21st Century Washington, DC National Academy Press, Institute of Medicine2001;
Ko  DTMamdani  MAlter  DA Lipid-lowering therapy with statins in high-risk elderly patients: the treatment-risk paradox. JAMA 2004;2911864- 1870
PubMed Link to Article
Goldman  LWeinstein  MCGoldman  PAWilliams  LW Cost-effectiveness of HMG-CoA reductase inhibition for primary and secondary prevention of coronary heart disease. JAMA 1991;2651145- 1151
PubMed Link to Article
Rahme  EMarentette  MAKong  SXLelorier  J Use of NSAIDs, COX-2 inhibitors, and acetaminophen and associated coprescriptions of gastroprotective agents in an elderly population. Arthritis Rheum 2002;47595- 602
PubMed Link to Article
Solomon  DHSchneeweiss  SGlynn  RJLevin  RAvorn  J Determinants of selective cyclooxygenase-2 inhibitor prescribing: are patient or physician characteristics more important? Am J Med 2003;115715- 720
PubMed Link to Article
Bennett  KTeeling  MFeely  J “Selective” switching from nonselective to selective nonsteroidal anti-inflammatory drugs. Eur J Clin Pharmacol 2003;59645- 649
PubMed Link to Article
Cutts  CLaCaze  ATett  S A clinical audit of the prescribing of celecoxib and rofecoxib in Australian rural general practice. Br J Clin Pharmacol 2002;54522- 527
PubMed Link to Article
Patino  FGAllison  JOlivieri  J The effects of physician specialty and patient comorbidities on the use and discontinuation of coxibs. Arthritis Rheum 2003;49293- 299
PubMed Link to Article
Gonzales  RSteiner  JFSande  MA Antibiotic prescribing for adults with colds, upper respiratory tract infections, and bronchitis by ambulatory care physicians. JAMA 1997;278901- 904
PubMed Link to Article
Federman  ADAdams  ASRoss-Degnan  DSoumerai  SBAyanian  JZ Supplemental insurance and use of effective cardiovascular drugs among elderly Medicare beneficiaries with coronary heart disease. JAMA 2001;2861732- 1739
PubMed Link to Article
Poisal  JChulis  G Medicare beneficiaries and drug coverage. Health Aff (Millwood) 2000;19248- 256
PubMed Link to Article
 Cherry DK, Burt CW, Woodwell DA. National Ambulatory Medical Care Survey 2001 Summary Hyattsville, Md National Center for Health Statistics2003;Advance Data From Vital Health and Statistics, No. 337
 Hing E, Middleton K. National Hospital Ambulatory Medical Care Survey: 2001 Outpatient Department Summary Hyattsville, Md National Center for Health Statistics2003;Advance Data From Vital Health and Statistics, No. 338
Doshi  JABrandt  NStuart  B The impact of drug coverage on COX-2 inhibitor use in medicare [Epub ahead of print]. Health Aff (Millwood) 2000;(Feb 18)W4-94- W4-104Available at: http://content.healthaffairs.org/cgi/reprint/hlthaff.w4.94v1.pdf. Accessed June 8, 2004
Singh  GTriadafilopoulos  GBrown  BBalise  R GI score: a simple self-assessment instrument to quantify the risk of serious NSAID-related GI complications in RA and OA. Arthritis Rheum 1998;41S59
Weston  APConnor  MMitreva  DSharma  P NSAID GI mucosal toxicity and SINGH score classification in veterans hospital: is it being followed and is the scoring system effective? [abstract] Arthritis Rheum 2003;48 ((suppl)) S607
Hosmer  DWLemeshow  S Applied Logistic Regression. 2nd ed. New York, NY John Wiley & Sons Inc2000;
Nystedt  PLyttkens  CH Age diffusion never stops? carotid endarterectomy among the elderly. Appl Health Econ Health Policy 2003;23- 7
PubMed
Legorreta  APSilber  JHCostantino  GNKobylinski  RWZatz  SL Increased cholecystectomy rate after the introduction of laparoscopic cholecystectomy. JAMA 1993;2701429- 1432
PubMed Link to Article
Muller  C The overmedicated society: forces in the marketplace for medical care. Science 1972;176488- 492
PubMed Link to Article
Grabowski  HVernon  J Brand loyalty, entry, and price competition in pharmaceuticals after the 1984 Drug Act. J Law Econ 1992;35331- 350
Link to Article
Rosenthal  MBBerndt  ERDonohue  JMFrank  RGEpstein  AM Promotion of prescription drugs to consumers. N Engl J Med 2002;346498- 505
PubMed Link to Article
Wosinska  M Just What the Patient Ordered? Direct-to-Consumer Advertising and the Demand for Pharmaceutical Products.  Boston, Mass Harvard Business School October2002;Harvard Business School Marketing Unit, Research Paper Series No. 02-04
Berndt  ERBhattacharjya  AMishol  DNArcelus  ALasky  T An analysis of the diffusion of new antidepressants: variety, quality, and marketing efforts. J Ment Health Policy Econ 2002;53- 19
PubMed
Landsberg  PGPillans  PIRadford  JM Evaluations of cyclooxygenase 2 inhibitor use in patients admitted to a large teaching hospital. Intern Med J 2003;33225- 228
PubMed Link to Article
Piette  JDHeisler  MWagner  TH Cost-related medication under-use: do patients with chronic illnesses tell their doctors? Arch Intern Med 2004;1641749- 1755
PubMed Link to Article
Maetzel  AKrahn  MNaglie  G The cost-effectiveness of rofecoxib and celecoxib in patients with osteoarthritis or rheumatoid arthritis. Arthritis Rheum 2003;49283- 292
PubMed Link to Article
Spiegel  BMTargownik  LDulai  GSGralnek  IM The cost-effectiveness of cyclooxygenase-2 selective inhibitors in the management of chronic arthritis. Ann Intern Med 2003;138795- 806
PubMed Link to Article
Chernew  MFendrick  AMHirth  RA Managed care and medical technology: implications for cost growth. Health Aff (Millwood) 1997;16196- 206
PubMed Link to Article
Leidl  RM Some factors to consider when using the results of economic evaluation studies at the population level. Int J Technol Assess Health Care 1994;10467- 478
PubMed Link to Article
Donohoe  MT Comparing generalist and specialty care: discrepancies, deficiencies, and excesses. Arch Intern Med 1998;1581596- 1608
PubMed Link to Article
Mazzuca  SABrandt  KDKatz  BP  et al.  Comparison of general internists, family physicians, and rheumatologists managing patients with symptoms of osteoarthritis of the knee. Arthritis Care Res 1997;10289- 299
PubMed Link to Article
Majumdar  SRInui  TSGurwitz  JHGillman  MWMcLaughlin  TJSoumerai  SB Influence of physician specialty on adoption and relinquishment of calcium channel blockers and other treatments for myocardial infarction. J Gen Intern Med 2001;16351- 359
PubMed Link to Article
Harrold  LRField  TSGurwitz  JH Knowledge, patterns of care, and outcomes of care for generalists and specialists. J Gen Intern Med 1999;14499- 511
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure.

Cyclooxygenase-2 inhibitor use stratified by risk of adverse events from nonsteroidal anti-inflammatory drugs (1999-2002).

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Characteristics of Patient Visits With COX-2 Inhibitor or NSAID Use (1999-2002)*
Table Graphic Jump LocationTable 2. National Visit Estimates With COX-2 Inhibitor or NSAID Use (1999-2002)*
Table Graphic Jump LocationTable 3. Use of COX-2 Inhibitors Stratified by Risk of Adverse GI Events From NSAIDs (1999-2002)*
Table Graphic Jump LocationTable 4. National Visit Estimates With COX-2 Inhibitor or NSAID Use Among Patients With Congestive Heart Failure, Liver Dysfunction, or Renal Dysfunction (1999-2002)*
Table Graphic Jump LocationTable 5. Association Between Patient, Physician, and Visit Characteristics and COX-2 Inhibitor Use (1999-2002)*

References

Silverstein  FEFaich  GGoldstein  JL  et al.  Gastrointestinal toxicity with celecoxib vs. nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. JAMA 2000;2841247- 1255
PubMed Link to Article
Bombardier  CLaine  LReicin  A  et al. VIGOR Study Group, Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med 2000;3431520- 1528
PubMed Link to Article
Mukherjee  DNissen  SETopol  EJ Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 2001;286954- 959
PubMed Link to Article
 Drug Topics Redbook 2003.  Montvale, NJ Medical Economics Co2003;
Marshall  JKPellissier  JMAttard  CLKong  SXMarentette  MA Cost-effectiveness analysis comparing rofecoxib with nonselective NSAIDs in osteoarthritis. Pharmacoeconomics 2001;191039- 1049
PubMed Link to Article
American Academy of Orthopaedic Surgeons, AAOS Clinical Practice Guideline on Osteoarthritis of the Knee.  Rosemont, Ill American Academy of Orthopaedic Surgeons2003;17
National Institute for Clinical Excellence, Guidance on the Use of Cyclo-oxygenase (Cox) II Selective Inhibitors, Celecoxib, Rofecoxib, Meloxicam, and Etodolac for Osteoarthritis and Rheumatoid Arthritis.  London, England National Institute for Clinical Excellence2001;1- 14Technology Appraised Guidance No. 27
The National Institute for Health Care Management Research and Education Foundation, Factors Affecting the Growth of Prescription Drug Expenditures.  Washington, DC The National Institute for Health Care Management Research and Education Foundation July9 1999;
Alexander  GCCasalino  LPMeltzer  DO Patient-physician communication about out-of-pocket costs. JAMA 2003;290953- 958
PubMed Link to Article
Berwick  DM Disseminating innovations in health care. JAMA 2003;2891969- 1975
PubMed Link to Article
 Institute of Medicine Committee on Health Care in America. Crossing the Quality Chasm A New Health System for the 21st Century Washington, DC National Academy Press, Institute of Medicine2001;
Ko  DTMamdani  MAlter  DA Lipid-lowering therapy with statins in high-risk elderly patients: the treatment-risk paradox. JAMA 2004;2911864- 1870
PubMed Link to Article
Goldman  LWeinstein  MCGoldman  PAWilliams  LW Cost-effectiveness of HMG-CoA reductase inhibition for primary and secondary prevention of coronary heart disease. JAMA 1991;2651145- 1151
PubMed Link to Article
Rahme  EMarentette  MAKong  SXLelorier  J Use of NSAIDs, COX-2 inhibitors, and acetaminophen and associated coprescriptions of gastroprotective agents in an elderly population. Arthritis Rheum 2002;47595- 602
PubMed Link to Article
Solomon  DHSchneeweiss  SGlynn  RJLevin  RAvorn  J Determinants of selective cyclooxygenase-2 inhibitor prescribing: are patient or physician characteristics more important? Am J Med 2003;115715- 720
PubMed Link to Article
Bennett  KTeeling  MFeely  J “Selective” switching from nonselective to selective nonsteroidal anti-inflammatory drugs. Eur J Clin Pharmacol 2003;59645- 649
PubMed Link to Article
Cutts  CLaCaze  ATett  S A clinical audit of the prescribing of celecoxib and rofecoxib in Australian rural general practice. Br J Clin Pharmacol 2002;54522- 527
PubMed Link to Article
Patino  FGAllison  JOlivieri  J The effects of physician specialty and patient comorbidities on the use and discontinuation of coxibs. Arthritis Rheum 2003;49293- 299
PubMed Link to Article
Gonzales  RSteiner  JFSande  MA Antibiotic prescribing for adults with colds, upper respiratory tract infections, and bronchitis by ambulatory care physicians. JAMA 1997;278901- 904
PubMed Link to Article
Federman  ADAdams  ASRoss-Degnan  DSoumerai  SBAyanian  JZ Supplemental insurance and use of effective cardiovascular drugs among elderly Medicare beneficiaries with coronary heart disease. JAMA 2001;2861732- 1739
PubMed Link to Article
Poisal  JChulis  G Medicare beneficiaries and drug coverage. Health Aff (Millwood) 2000;19248- 256
PubMed Link to Article
 Cherry DK, Burt CW, Woodwell DA. National Ambulatory Medical Care Survey 2001 Summary Hyattsville, Md National Center for Health Statistics2003;Advance Data From Vital Health and Statistics, No. 337
 Hing E, Middleton K. National Hospital Ambulatory Medical Care Survey: 2001 Outpatient Department Summary Hyattsville, Md National Center for Health Statistics2003;Advance Data From Vital Health and Statistics, No. 338
Doshi  JABrandt  NStuart  B The impact of drug coverage on COX-2 inhibitor use in medicare [Epub ahead of print]. Health Aff (Millwood) 2000;(Feb 18)W4-94- W4-104Available at: http://content.healthaffairs.org/cgi/reprint/hlthaff.w4.94v1.pdf. Accessed June 8, 2004
Singh  GTriadafilopoulos  GBrown  BBalise  R GI score: a simple self-assessment instrument to quantify the risk of serious NSAID-related GI complications in RA and OA. Arthritis Rheum 1998;41S59
Weston  APConnor  MMitreva  DSharma  P NSAID GI mucosal toxicity and SINGH score classification in veterans hospital: is it being followed and is the scoring system effective? [abstract] Arthritis Rheum 2003;48 ((suppl)) S607
Hosmer  DWLemeshow  S Applied Logistic Regression. 2nd ed. New York, NY John Wiley & Sons Inc2000;
Nystedt  PLyttkens  CH Age diffusion never stops? carotid endarterectomy among the elderly. Appl Health Econ Health Policy 2003;23- 7
PubMed
Legorreta  APSilber  JHCostantino  GNKobylinski  RWZatz  SL Increased cholecystectomy rate after the introduction of laparoscopic cholecystectomy. JAMA 1993;2701429- 1432
PubMed Link to Article
Muller  C The overmedicated society: forces in the marketplace for medical care. Science 1972;176488- 492
PubMed Link to Article
Grabowski  HVernon  J Brand loyalty, entry, and price competition in pharmaceuticals after the 1984 Drug Act. J Law Econ 1992;35331- 350
Link to Article
Rosenthal  MBBerndt  ERDonohue  JMFrank  RGEpstein  AM Promotion of prescription drugs to consumers. N Engl J Med 2002;346498- 505
PubMed Link to Article
Wosinska  M Just What the Patient Ordered? Direct-to-Consumer Advertising and the Demand for Pharmaceutical Products.  Boston, Mass Harvard Business School October2002;Harvard Business School Marketing Unit, Research Paper Series No. 02-04
Berndt  ERBhattacharjya  AMishol  DNArcelus  ALasky  T An analysis of the diffusion of new antidepressants: variety, quality, and marketing efforts. J Ment Health Policy Econ 2002;53- 19
PubMed
Landsberg  PGPillans  PIRadford  JM Evaluations of cyclooxygenase 2 inhibitor use in patients admitted to a large teaching hospital. Intern Med J 2003;33225- 228
PubMed Link to Article
Piette  JDHeisler  MWagner  TH Cost-related medication under-use: do patients with chronic illnesses tell their doctors? Arch Intern Med 2004;1641749- 1755
PubMed Link to Article
Maetzel  AKrahn  MNaglie  G The cost-effectiveness of rofecoxib and celecoxib in patients with osteoarthritis or rheumatoid arthritis. Arthritis Rheum 2003;49283- 292
PubMed Link to Article
Spiegel  BMTargownik  LDulai  GSGralnek  IM The cost-effectiveness of cyclooxygenase-2 selective inhibitors in the management of chronic arthritis. Ann Intern Med 2003;138795- 806
PubMed Link to Article
Chernew  MFendrick  AMHirth  RA Managed care and medical technology: implications for cost growth. Health Aff (Millwood) 1997;16196- 206
PubMed Link to Article
Leidl  RM Some factors to consider when using the results of economic evaluation studies at the population level. Int J Technol Assess Health Care 1994;10467- 478
PubMed Link to Article
Donohoe  MT Comparing generalist and specialty care: discrepancies, deficiencies, and excesses. Arch Intern Med 1998;1581596- 1608
PubMed Link to Article
Mazzuca  SABrandt  KDKatz  BP  et al.  Comparison of general internists, family physicians, and rheumatologists managing patients with symptoms of osteoarthritis of the knee. Arthritis Care Res 1997;10289- 299
PubMed Link to Article
Majumdar  SRInui  TSGurwitz  JHGillman  MWMcLaughlin  TJSoumerai  SB Influence of physician specialty on adoption and relinquishment of calcium channel blockers and other treatments for myocardial infarction. J Gen Intern Med 2001;16351- 359
PubMed Link to Article
Harrold  LRField  TSGurwitz  JH Knowledge, patterns of care, and outcomes of care for generalists and specialists. J Gen Intern Med 1999;14499- 511
PubMed Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 81

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles