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The pattern of topical corticosteroid prescribing in the United States, 1989–1991
The pattern of topical corticosteroid prescribing in the United States, 1989-1991 Robert S. Stem, MD Boston, Massachusetts Background: Topical corticosteroids are widely used in the treatment of skin diseases. These preparations vary greatly in potency. They are available in both brand name and generic formulations, as well as in combination products. Objective: Our purpose was to determine the pattern of topical corticosteroids prescribing in the United States and the relation of patient and prescriber attributes to the type of corticosteroid preparation prescribed. Methods: Data from the 1989 to 1991 National Ambulatory Medical Care Survey were used to estimate the number of visits with a topical corticosteroid preparation prescribed and to identify prescribers with specific characteristics. Results: In the United States, topical corticosteroids are prescribed or recommended at an average of 14 million visits per year to office-based health practitioners. Forty percent of these visits were to dermatologists. Dermatologists were 3.9 times more likely to prescribe very high potency steroids than were other physicians. Physicians other than dermatologists were 8.4 times more likely than dermatologists to prescribe combination agents contahfing moderate- or high-potency topical corticosteroids and an antiinfective agent. Conclusion: The pattern of topical corticosteroid prescribing is substantially different for dermatologists and other physicians. These differences may reflect differences in severity or complexity of the disease or differences in prescribing habits. The importance of these differences to the outcome of treated patients is not established. (J Am Acad Dermatol 1996;35:183-6.) Topical corticosteroids are among the most widely prescribed agents in ambulatory medicine. From 1989 to 1991, at least 17 different chemical entities were marketed as topical corticosteroids in the United States. 1-3 Most were available in various concentrations and dosage forms (creams, lotions, ointments, gels, solutions) and m a n y were available generically. In addition, some topical corticosteroids were available as fixed combinations with antiinfective agents. As a result, the physician must choose among hundreds of drugs, concentrations, combinations, and dosage forms, many of which are provided under a variety of brand and generic names. The cost per dose of topical corticosteroids varies as much as 100-fold depending on the quantity and type of preparation dispensed. 4 Both multiple brand
name and generic preparations are available for all potency categories except very high potency agents, which, in 1989 to 1991, were available only as brand name products. In general, the average wholesale price of brand name topical corticosteroids is threefold to fourfold higher than that of generic products containing the same active agent. 4 Despite their frequent use, tittle is known about the association of prescriber or patient characteristics and the rates of use of very high potency, generic, or combination topical corticosteroid agents. With data from the National Ambulatory Medical Care Survey (NAMCS), we describe office-based physicians' prescribing of topical corticosteroids in the United States from 1989 to 1991. METHODS
From the Deparlrnent of Dermatology, Beth Israel Hospital, Harvard Medical School, and the Charles Dana Research Foundation of the Beth Israel Hospital. Accepted for publication Jan. 17, 1996. Reprint requests: Robert S. Stem, MD, Beth Israel Hospital, 330 Brookline Ave., Boston, MA 02215. Copyright © 1996 by the American Academy of Dermatology, Inc. 0190-9622/96 $5.00 + 0 16/1/72052
The NAMCS is a multistage probability sample survey of ambulatory nonfederal physicians in office-based practice. 5 Each participating physician completes a survey insmmaent for each patient visit during the sampling. From 1989 to 1991, a total of 115,648 visits to participating physicians were sampled. The NAMCS insmmaent allows the recording of up to 183
184
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Stern
Table II. Percentage of all office visits to physicians that include dispensing a topical corticosteroid, by physician specialty
T a b l e I. Annual prescriptions for topical corticosteroids by potency* Prescriptions No., in Potency
millions
%
Low Medium High Very high
2.2 6.0 5.0 1.5
15 41 34 10
*U.S. Pharmacopeia classification of potency. Combination agents are classified according to potency of topical corticosteroid component. 1
four diagnoses and three patient complaints/This survey instrument also includes demographic data of the patients, expected source of payment, whether the patient was referred, disposition of the patient, and up to five medications prescribed during the visit. Given the nature of sampling, each visit can be assigned a weight so that the total number of visits in that year with those characteristics (i.e., for that diagnosis or with that medication prescribed or by patients with a given demographic characteristic) can be estimated. 5 The National Center for Health Statistics also publishes tables and formulas that permit estimation of the relative standard error of means. We utilized these relative standard errors to test for statistical significance of differences between groups based on the t test.5 Because this study represents 3 years of survey data, standard errors were adjusted to reflect pooling of data for these 3 years. On the basis of these NAMCS data, the number of prescriptions for patients receiving specific topical corticosteroids including those that are classified as very high potency, combination agents, or available generically was calculated. The characteristics of prescribers of each of these classes of topical corticosteroids was also quantified. RESULTS From 1989 to 1991, office-based physicians prescribed or recommended at least one topical corticosteroid at an average of 14,300,000 visits each year. In 93% of such visits, only a single corticosteroid prescription was dispensed. In 6% of these visits two different corticosteroids were dispensed, and in 1% of visits three or more different corticosteroid prescriptions were provided to the patient. Unless otherwise noted, only the first listed topical corticosteroid is tabulated in our analyses. In Table i, the average number of prescriptions per year for each U.S. Pharmacopeia potency categorization is listed. 1 The
Specialty
% All visits
Dermatology Pediatricians Family and general physicians Internists Other office-based physicians All office visits, all specialties
21.0 2.0 1.9 1.5 0.7 2.0
percent of all visits at which a topical corticosteroid was ordered varies greatly among specialties, but exceeds 5% only for visits to dermatologists. More than one visit in five to a dermatologist included a topical corticosteroid prescription (Table I1). From 1989 to 1991, very high potency corticosteroids were not available as generic products. For low-, medium-, and high-potency topical corticosteroids, preparations for which generic substitution was possible were prescribed at 87%, 84%, and 36% of visits with prescriptions for such agents, respectively. The rate of prescribing of topical steroids with generic substitutes available varied significantly among geographic location of the United States. Physicians in the Northeast and North Central states were significantly less likely to prescribe corticosteroids for which generic substitution is available (60%) compared with physicians practicing in the South and West (71%) (p < 0.05). Doctors of osteopathy were significantly less likely to prescribe drugs for which generic substitution is available than were doctors of medicine (57% vs 67%). Internists as well as family and general physicians were less likely to prescribe agents with available generic substitutions than were dermatologists and pediatricians (60% vs 70%) (p < 0.05). For patients younger than 6 years of age, pediatricians accounted for 61% of visits with a topical corticosteroid prescription and dermatologists for 12% of such visits. For patients younger than 13 years of age, pediatricians accounted for 55% of topical corticosteroid prescriptions and dermatologists for 19%. Table Ill demonstrates the higher proportion of patients older than 6 years of age who were prescribed very high potency topical steroids by a dermatologist. Physicians other than dermatologists were five to seven times more likely to prescribe combination agents than were dermatologists (p < 0.05) (Table
Journal of the American Academy of Dermatology Volmne 35, Number 2, Part 1
Stern
Table III. Percentage of patients treated with a topical corticosteroid who were prescribed a very high potency drug, by age of patient and type of prescriber
Table IV. Percentage of all visits with a topical corticosteroid dispensed, by type of agent prescribed and physician specialty Potency of eorticosteroid only
Age of patient (yr) Prescriber
<6
[ 6-19
20-64
65+
All
Dermatologist Other Physicians'~ All physicians
* 0.5%
14% 5%
26% 8%
15% 6%
20% 6%
1%
8%
15%
10%
11%
*Too few cases to estimate. tPhysicians other than dermatologists.
IV). For patients younger than 6 years of age, pediatricians prescribed a medium- or high-potency topical corticosteroid as a combination product (i.e., with a topical antiinfective agent) in 39% of such visits, and other nondermatologists relied on combination agents in more than half of such visits. Dermatologists advised combination agents at only 17% of visits during which a medium- or high-potency corticosteroid was prescribed to a child younger than 6 years old. DISCUSSION
The prescribing physician is faced with numerous choices as to which topical corticosteroid should be prescribed for a patient with a potentially corticostetold-responsive dermatosis. Both nondermatologists and dermatologists frequently prescribed these agents. The 14 million office visits each year associated with a topical corticosteroid prescription document the wide use of these agents. However, data that assure us that generic topical corticosteroids provide equivalent therapeutic effects or demonstrate that higher potency products have sufficiently increased efficacy or, more importantly, higher benefit/risk ratios to outweigh their high costs and possibly greater risks are largely lacking. 6-9 Rates of prescribing of agents for which generic substitution is not possible, including rates of recommending very high potency agents or some fixed (topical corticosteroid/topical antiinfective) combination agents, vary among physicians of different specialties and among patients treated in different regions of the country. For children, use of combination agents is especially frequent. Visits to dermatologists accounted for 40% of
185
Low~
Fixed comblnationt
medium,
Very high
Prescriber
high* (%)
(%)
(%)
Dermatologists Pediatricians General and family medicine Internal medicine Other physicians
76 75 68
20 2 6
4 23 26
68 68
8 8
24 24
*All 1% hydrocortisone-containing agents included in this category. -~Includinga medium or higher potency corticosteroid and antiinfecfive agent.
visits at which topical corticosteroids were prescribed. The different pattern of prescribing of topical corticosteroids by dermatologists and nondermatologists raises questions concerning the optimal treatment of cutaneous disease. Differences in prescribing habits among specialties may reflect differences in the complexity or severity of illness among patients presenting with skin disease to physicians with different specialty training, or it may reflect other factors, such as the expertise of the prescribing physician. In general, the pattern of use of topical corticosteroids categorized either by potency (with the U.S. Pharmacopeia classification) 1 or according to whether a combination agent (i.e., topical corticosteroid plus antiinfective agent was utilized) was similar for all nondermatologists. Dermatologists were far more likely to prescribe very high potency topical corticosteroids than other physicians and less likely to prescribe combination products. Dermatologists' more frequent use of prescribing very high potency agents might reflect greater experience in the treatment of skin disease and greater comfort with the use of more potent agents or greater severity of disease among patients seen by dermatologists compared with patients thought to have corticosteroid-responsive dermatoses seen by other physicians. Dermatologists may have a more aggressive therapeutic approach than other physicians. Nondermatologists prescribe combination corticosteroid/antiinfective products far more frequently than dermatologists. This suggests that these physicians may be less sure of whether a skin problem they treat is inflammatory, infectious,
186
Stern
or both. Alternatively, these agents may have gained greater acceptance or received greater promotion among these specialties. Unfortunately, our survey of usage does not permit us to determine which of these explanations are important or what other factors might explain dermatologists' far more frequent use of very high potency topical corticosteroids and greater reliance on combination agents by other specialists and general physicians. For approximately 10% of visits at which a topical corticosteroid was prescribed, generic substitution was not available because very high potency agents were prescribed. For prescriptions of topical corticosteroids in lower potency categories, an agent for which a generic substitute was available was prescribed during approximately two thirds of such visits. Although generic substitution was available for the majority of prescriptions, we lacked data on the percentage of such potentially substitutable prescriptions that were, in fact, dispensed as brand name or generic preparations. Most important, despite the hundreds of millions of dollars spent on topical corticosteroids, we lack data on whether generic substitutes are, in fact, therapeutically equivalent in terms of clinical acceptance and response. 8' 9 Clearly, data that would assure us that the less expensive generic products are as effective in clinical practice as brand name products of the same potency would provide a compelling argument for increased utilization of generic products. Alternatively, data that demonstrate generic products are less effective or less acceptable to patients than their brand name competitors might well justify the higher cost of brand products. The cost of physicians' services and pharmaceuticals prescribed at visits to physicians that include a topical corticosteroid prescription undoubtedly exceeds $1 billion per year. However, guidelines for optimizing therapy and for rational prescribing with respect to the choice of a specific agent or even the
Journal of the American Academy of Dermatology August 1996
selection of which potency of topical corticosteroid is best for the individual patient are not well established. Our data demonstrate substantial differences in the pattern of use of the most commonly prescribed drugs for treatment of skin disease among physicians with different training. Establishing the extent to which these differences in prescribing pattern reflect differences in the type of patients treated and the extent that the choice of a particular topical corticosteroid influences the outcome of care could help establish whether services provided by nonspecialists are, in fact, equivalent to those provided by dermatologists to patients with many common skin diseases. REFERENCES
1. Drag information for the health care professional, 1994; vol 1. Rockville, MD: United States Pharmacopeia, Inc, 1994:3351. 2. Stoughton RB. Vasoconstrictor activity and percutaneous absorption of glucocorticosteroids: a direct comparison. Arch Dermatol 1969;99:753-6. 3. Comell RC, Stoughton RB. Correlation of the vasoconstriction assay and clinical activity in psoriasis. Arch Dermatol 1985;121:63-7. 4. Beth Israel Hospital: drug dictionary. Boston: Clinical Computing System, 1995. 5. Delozier JE, Gaguon RO. National Ambulatory Medical Care Survey: 1989 summary. Vital and Health Statistics of the National Center for Health Statistics. No. 203. Hyattsville, MD: US Department Health and Human Services, 1994. 6. Stoughton RB. Are generic formulations equivalent to trade name topical glucocorticoids? Arch Dermatol 1987; 123:1312-4. 7. Olsen EA. A double-blind controlled comparison of generic and trade-name topical steroids using the vasoconstriction assay. Arch Derrnatol 1991;127:197-201. 8. Stoughton RB. The vasoconstrictor assay in bioeqnivalence testing: practical concerns and recent developments. Int J Dermatol 1992;31:26-8. 9. Guin JD, Wallis MS, Walls R, et al. Quantitative vasoconstrictor assay for topical corticosteroids: the puzzling case of finocinolone acetonide. J Am Acad Dermatol 1993; 29:197-202.
name and generic preparations are available for all potency categories except very high potency agents, which, in 1989 to 1991, were available only as brand name products. In general, the average wholesale price of brand name topical corticosteroids is threefold to fourfold higher than that of generic products containing the same active agent. 4 Despite their frequent use, tittle is known about the association of prescriber or patient characteristics and the rates of use of very high potency, generic, or combination topical corticosteroid agents. With data from the National Ambulatory Medical Care Survey (NAMCS), we describe office-based physicians' prescribing of topical corticosteroids in the United States from 1989 to 1991. METHODS
From the Deparlrnent of Dermatology, Beth Israel Hospital, Harvard Medical School, and the Charles Dana Research Foundation of the Beth Israel Hospital. Accepted for publication Jan. 17, 1996. Reprint requests: Robert S. Stem, MD, Beth Israel Hospital, 330 Brookline Ave., Boston, MA 02215. Copyright © 1996 by the American Academy of Dermatology, Inc. 0190-9622/96 $5.00 + 0 16/1/72052
The NAMCS is a multistage probability sample survey of ambulatory nonfederal physicians in office-based practice. 5 Each participating physician completes a survey insmmaent for each patient visit during the sampling. From 1989 to 1991, a total of 115,648 visits to participating physicians were sampled. The NAMCS insmmaent allows the recording of up to 183
184
Journal of the American Academy of Dermatology August 1996
Stern
Table II. Percentage of all office visits to physicians that include dispensing a topical corticosteroid, by physician specialty
T a b l e I. Annual prescriptions for topical corticosteroids by potency* Prescriptions No., in Potency
millions
%
Low Medium High Very high
2.2 6.0 5.0 1.5
15 41 34 10
*U.S. Pharmacopeia classification of potency. Combination agents are classified according to potency of topical corticosteroid component. 1
four diagnoses and three patient complaints/This survey instrument also includes demographic data of the patients, expected source of payment, whether the patient was referred, disposition of the patient, and up to five medications prescribed during the visit. Given the nature of sampling, each visit can be assigned a weight so that the total number of visits in that year with those characteristics (i.e., for that diagnosis or with that medication prescribed or by patients with a given demographic characteristic) can be estimated. 5 The National Center for Health Statistics also publishes tables and formulas that permit estimation of the relative standard error of means. We utilized these relative standard errors to test for statistical significance of differences between groups based on the t test.5 Because this study represents 3 years of survey data, standard errors were adjusted to reflect pooling of data for these 3 years. On the basis of these NAMCS data, the number of prescriptions for patients receiving specific topical corticosteroids including those that are classified as very high potency, combination agents, or available generically was calculated. The characteristics of prescribers of each of these classes of topical corticosteroids was also quantified. RESULTS From 1989 to 1991, office-based physicians prescribed or recommended at least one topical corticosteroid at an average of 14,300,000 visits each year. In 93% of such visits, only a single corticosteroid prescription was dispensed. In 6% of these visits two different corticosteroids were dispensed, and in 1% of visits three or more different corticosteroid prescriptions were provided to the patient. Unless otherwise noted, only the first listed topical corticosteroid is tabulated in our analyses. In Table i, the average number of prescriptions per year for each U.S. Pharmacopeia potency categorization is listed. 1 The
Specialty
% All visits
Dermatology Pediatricians Family and general physicians Internists Other office-based physicians All office visits, all specialties
21.0 2.0 1.9 1.5 0.7 2.0
percent of all visits at which a topical corticosteroid was ordered varies greatly among specialties, but exceeds 5% only for visits to dermatologists. More than one visit in five to a dermatologist included a topical corticosteroid prescription (Table I1). From 1989 to 1991, very high potency corticosteroids were not available as generic products. For low-, medium-, and high-potency topical corticosteroids, preparations for which generic substitution was possible were prescribed at 87%, 84%, and 36% of visits with prescriptions for such agents, respectively. The rate of prescribing of topical steroids with generic substitutes available varied significantly among geographic location of the United States. Physicians in the Northeast and North Central states were significantly less likely to prescribe corticosteroids for which generic substitution is available (60%) compared with physicians practicing in the South and West (71%) (p < 0.05). Doctors of osteopathy were significantly less likely to prescribe drugs for which generic substitution is available than were doctors of medicine (57% vs 67%). Internists as well as family and general physicians were less likely to prescribe agents with available generic substitutions than were dermatologists and pediatricians (60% vs 70%) (p < 0.05). For patients younger than 6 years of age, pediatricians accounted for 61% of visits with a topical corticosteroid prescription and dermatologists for 12% of such visits. For patients younger than 13 years of age, pediatricians accounted for 55% of topical corticosteroid prescriptions and dermatologists for 19%. Table Ill demonstrates the higher proportion of patients older than 6 years of age who were prescribed very high potency topical steroids by a dermatologist. Physicians other than dermatologists were five to seven times more likely to prescribe combination agents than were dermatologists (p < 0.05) (Table
Journal of the American Academy of Dermatology Volmne 35, Number 2, Part 1
Stern
Table III. Percentage of patients treated with a topical corticosteroid who were prescribed a very high potency drug, by age of patient and type of prescriber
Table IV. Percentage of all visits with a topical corticosteroid dispensed, by type of agent prescribed and physician specialty Potency of eorticosteroid only
Age of patient (yr) Prescriber
<6
[ 6-19
20-64
65+
All
Dermatologist Other Physicians'~ All physicians
* 0.5%
14% 5%
26% 8%
15% 6%
20% 6%
1%
8%
15%
10%
11%
*Too few cases to estimate. tPhysicians other than dermatologists.
IV). For patients younger than 6 years of age, pediatricians prescribed a medium- or high-potency topical corticosteroid as a combination product (i.e., with a topical antiinfective agent) in 39% of such visits, and other nondermatologists relied on combination agents in more than half of such visits. Dermatologists advised combination agents at only 17% of visits during which a medium- or high-potency corticosteroid was prescribed to a child younger than 6 years old. DISCUSSION
The prescribing physician is faced with numerous choices as to which topical corticosteroid should be prescribed for a patient with a potentially corticostetold-responsive dermatosis. Both nondermatologists and dermatologists frequently prescribed these agents. The 14 million office visits each year associated with a topical corticosteroid prescription document the wide use of these agents. However, data that assure us that generic topical corticosteroids provide equivalent therapeutic effects or demonstrate that higher potency products have sufficiently increased efficacy or, more importantly, higher benefit/risk ratios to outweigh their high costs and possibly greater risks are largely lacking. 6-9 Rates of prescribing of agents for which generic substitution is not possible, including rates of recommending very high potency agents or some fixed (topical corticosteroid/topical antiinfective) combination agents, vary among physicians of different specialties and among patients treated in different regions of the country. For children, use of combination agents is especially frequent. Visits to dermatologists accounted for 40% of
185
Low~
Fixed comblnationt
medium,
Very high
Prescriber
high* (%)
(%)
(%)
Dermatologists Pediatricians General and family medicine Internal medicine Other physicians
76 75 68
20 2 6
4 23 26
68 68
8 8
24 24
*All 1% hydrocortisone-containing agents included in this category. -~Includinga medium or higher potency corticosteroid and antiinfecfive agent.
visits at which topical corticosteroids were prescribed. The different pattern of prescribing of topical corticosteroids by dermatologists and nondermatologists raises questions concerning the optimal treatment of cutaneous disease. Differences in prescribing habits among specialties may reflect differences in the complexity or severity of illness among patients presenting with skin disease to physicians with different specialty training, or it may reflect other factors, such as the expertise of the prescribing physician. In general, the pattern of use of topical corticosteroids categorized either by potency (with the U.S. Pharmacopeia classification) 1 or according to whether a combination agent (i.e., topical corticosteroid plus antiinfective agent was utilized) was similar for all nondermatologists. Dermatologists were far more likely to prescribe very high potency topical corticosteroids than other physicians and less likely to prescribe combination products. Dermatologists' more frequent use of prescribing very high potency agents might reflect greater experience in the treatment of skin disease and greater comfort with the use of more potent agents or greater severity of disease among patients seen by dermatologists compared with patients thought to have corticosteroid-responsive dermatoses seen by other physicians. Dermatologists may have a more aggressive therapeutic approach than other physicians. Nondermatologists prescribe combination corticosteroid/antiinfective products far more frequently than dermatologists. This suggests that these physicians may be less sure of whether a skin problem they treat is inflammatory, infectious,
186
Stern
or both. Alternatively, these agents may have gained greater acceptance or received greater promotion among these specialties. Unfortunately, our survey of usage does not permit us to determine which of these explanations are important or what other factors might explain dermatologists' far more frequent use of very high potency topical corticosteroids and greater reliance on combination agents by other specialists and general physicians. For approximately 10% of visits at which a topical corticosteroid was prescribed, generic substitution was not available because very high potency agents were prescribed. For prescriptions of topical corticosteroids in lower potency categories, an agent for which a generic substitute was available was prescribed during approximately two thirds of such visits. Although generic substitution was available for the majority of prescriptions, we lacked data on the percentage of such potentially substitutable prescriptions that were, in fact, dispensed as brand name or generic preparations. Most important, despite the hundreds of millions of dollars spent on topical corticosteroids, we lack data on whether generic substitutes are, in fact, therapeutically equivalent in terms of clinical acceptance and response. 8' 9 Clearly, data that would assure us that the less expensive generic products are as effective in clinical practice as brand name products of the same potency would provide a compelling argument for increased utilization of generic products. Alternatively, data that demonstrate generic products are less effective or less acceptable to patients than their brand name competitors might well justify the higher cost of brand products. The cost of physicians' services and pharmaceuticals prescribed at visits to physicians that include a topical corticosteroid prescription undoubtedly exceeds $1 billion per year. However, guidelines for optimizing therapy and for rational prescribing with respect to the choice of a specific agent or even the
Journal of the American Academy of Dermatology August 1996
selection of which potency of topical corticosteroid is best for the individual patient are not well established. Our data demonstrate substantial differences in the pattern of use of the most commonly prescribed drugs for treatment of skin disease among physicians with different training. Establishing the extent to which these differences in prescribing pattern reflect differences in the type of patients treated and the extent that the choice of a particular topical corticosteroid influences the outcome of care could help establish whether services provided by nonspecialists are, in fact, equivalent to those provided by dermatologists to patients with many common skin diseases. REFERENCES
1. Drag information for the health care professional, 1994; vol 1. Rockville, MD: United States Pharmacopeia, Inc, 1994:3351. 2. Stoughton RB. Vasoconstrictor activity and percutaneous absorption of glucocorticosteroids: a direct comparison. Arch Dermatol 1969;99:753-6. 3. Comell RC, Stoughton RB. Correlation of the vasoconstriction assay and clinical activity in psoriasis. Arch Dermatol 1985;121:63-7. 4. Beth Israel Hospital: drug dictionary. Boston: Clinical Computing System, 1995. 5. Delozier JE, Gaguon RO. National Ambulatory Medical Care Survey: 1989 summary. Vital and Health Statistics of the National Center for Health Statistics. No. 203. Hyattsville, MD: US Department Health and Human Services, 1994. 6. Stoughton RB. Are generic formulations equivalent to trade name topical glucocorticoids? Arch Dermatol 1987; 123:1312-4. 7. Olsen EA. A double-blind controlled comparison of generic and trade-name topical steroids using the vasoconstriction assay. Arch Derrnatol 1991;127:197-201. 8. Stoughton RB. The vasoconstrictor assay in bioeqnivalence testing: practical concerns and recent developments. Int J Dermatol 1992;31:26-8. 9. Guin JD, Wallis MS, Walls R, et al. Quantitative vasoconstrictor assay for topical corticosteroids: the puzzling case of finocinolone acetonide. J Am Acad Dermatol 1993; 29:197-202.