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The annual cost of psoriasis
Journal of the American Academy of Dermatology Volume 30, Number 6
4. 5.
6.
7.
hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide.Proc Nat! Acad Sci USA 1990;87:1620-4. Weiss G, Fuchs D, Hausen A, et al. Neopterin modulates toxicity mediated by reactive oxygen and chloride species. FEBS Lett 1993;321:89-92. Bulpitt KJ, Clements PJ, Lachenbruch AP, et al. Early undifferentiated connective tissue disease. Ill. Outcome and prognostic indicators in early scleroderma. Ann Intern Moo 1993;118:602-9. Wachter H, Fuchs D, Hausen A, et at Neopterin as a marker for activation of cellular immunity: immunologic basis and clinical application. Adv Clin Chern 1989;27:81141. Werner-Felmayer G, Werner ER, Fuchs 0, et al. Neopterin formation and tryptophan degradation by a human myelomonocytic cell line (THP-l) upon cytokine treatment. Cancer Res 1990;50:2863-7.
The annual cost of psoriasis To the Editor: An article recently published in this JOUR"The Annual Cost of Psoriasis" (J AM ACAD DERMATOL 1993;28:422-5), attempted to address the need for comparative costs of psoriasis therapy. The article attracted our attention because psoriasis affects up to 2%of the U.S. population! and because its authors concluded that no treatment is universally superior although one, cyclosporine, is at least twice as costly. We reviewed this article to gain an understanding of the methodology used to arrive at this conclusion. The study, performed at the Baylor Psoriasis Center in Dallas, consisted of a retrospective analysis of 66 patients treated for psoriasis between 1983 and 1991. Comparators included three types of phototherapy (Goeckerman, PUVA, and outpatient UVB) and systemic treatment (methotrexate, etretinate, hydroxyurea, and cyclosporine). A chart review was performed, and patients were included if they met the criteria of monotherapy management and availability of the patient for follow-up for up to 1 year. Data from this review were used as the clinical input for a comparative cost analysis. Retrospective pharmacoeconomic evaluation has been demonstrated to be an effective method to evaluate the cost-effectiveness of drugs. Pharmacoeconomic studies have no "economic end points," but, rather, pharmacoeconomics is the valuing of clinical outcomes. As such, there are two principal choices for clinical inputs for a pharmacoeconomic study: (I) meta-analysis of the available clinical data and (2) chart reviews.Depending on the therapy under study, either one of these methods may be advantageous. Meta-analysis provides a rigorous method for evaluating clinical success rates, failure rates, relapse rates, and side-effect profiles through statistical techniques that combine results across studies. Depending on the field under study, these mayor may not represent the real world and should always be reviewed by expert clinicians for accuracy and applicability. Chart reviewsprovide real NAL,
Correspondence 1047 world data from completed cases, but to extrapolate these data to a population broader than just one institution or ward, a large sample size is required. The sample must be large enough to account for demographic issues as well as regional and even philosophical variations in the provision of medical care and its outcomes. We thus found it distressing that the Baylor study used only 66 charts in total, with as few as six charts being used for the cyclosporine evaluation. This small sample size cannot provide a real-world evaluation of the delivery of psoriasis therapy. Because selection criteria included management with monotherapy only, other choices were not considered. Moreover, the analysis did not consider clinical efficacy, but compared regimens as if they were all equal with regard to outcomes-in fact, assuming 100% effectiveness. Again, in the real world, products are not 100% effective. These observations and their implications render the Baylor study invalid. Study inclusion criteria included patients taking cyclosporine who, according to the authors, had a more recalcitrant form of psoriasis that was refractory to other therapies. Thus the study groups are not comparable, casting serious doubt on the validity of the findings. To properly evaluate the cost-effectiveness of a drug product, it is necessary to construct a decision analytic model that accounts for each therapeutic outcome (e.g., successful therapy with no relapse, successful therapy with subsequent relapse, failed therapy treated with a backup drug). In the case of psoriasis, at least eight such outcomes are possible, and each must be evaluated in terms of probability of occurrence and cost of outcome. The sum of these eight outcomes provides the overall cost of therapy with a drug. This type of full analysis can be accomplished through a chart review, but a significantly larger sample size is necessary. One would expect the average clinical trial to examine a minimum of 25 to 30 patients in each comparator group under study. If this basic principle were to be followed in a chart review, in which a significant amount of variation will exist among patient data, a sample size of at least 10 times that used in the Baylor study is necessary. Although the Baylor study uses the terms "cost-effective" and "cost-effectiveness" throughout the Discussion and Conclusions sections, it is not a cost-effectiveness analysis. Cost-effectiveness analysis provides real world pharmacoeconomic data by considering cost of therapy with overall effectiveness. The Baylor study is a comparative cost study. The study should not be used in making formulary decisions because it identifies costs without analyzing outcomes. Such analyses can be misleading to a decision maker because consideration of outcomes often leads to a change in rank order of comparators.
Steven R. Arikian, HID Thomas R. Einarson, PhD Faculty of Pharmacy University of Toronto
Journal of the American Academy of Dermatology June 1994
1048 Correspondence REFERENCE
I. Farber EM, Nall L. Psoriasis: a reviewof recent advances in treatment. Drugs 1984;28:324-46.
Reply To the Editor: One of the purposes of our publication was to generate discussion about the cost of psoriasis therapy and the role the cost of therapy should have in selection of a particular therapeutic modality. We therefore welcome criticism of our publication, either positive or negative. We agree that the ideal cost-effective study relating to psoriasis has not been performed; however, such a study is currently under way with appropriate statistical analyses from multiple centers. We still consider our study results worthwhile because of the following: 1. Effectiveness data were compared and were similar to previously published literature reports. 2. The cost data would likely be unchanged, even if the sample size were larger. For example, with cyclosporine, the cost of medication alone is almost four times higher than any other psoriasis medication. At a fixed dosage, the mean patient drug cost would not change if cyclosporine was used for the mildest cases of psoriasis, or if the sample size were 600 rather than 6 patients. Our cost data reflect a "best case scenario"; that is, the patients tolerated the medication wel1 enough to allow a l-year period of therapy and observation. We fully realize that other factors contributing to the cost of treatment were not included, such as the cost ofcare for complications related to therapy (worst case scenarios), such as the need for liver transplantation for liver failure after methotrexate therapy. We look forward to being able to publish future costcomparative and cost-effectiveness studies for psoriasis therapy and hope that this will also stimulate similar studies in other areas of dermatology. Hans M . Sander, .MD Austin Regional Clinic Austin, TX 78731 Alan Menter, MD Baylor University Medical Center Dallas, TX 75246
Alcohol abuse and treatment resistance in skin disease To the Editor: We were interested to read the report by Gupta et aI. on alcohol intake and its relation to treatment
response in psoriasis (J AM ACAD DERMATOL 1993; 28:730-2). We have also been studying the relation between alcohol and psoriasis and have found a much higher level of alcohol abuse in patients with psoriasis than in controls. We conclude that alcohol is a risk factor for the development of psoriasis in both men and women. I Like Gupta et aI., we have noted that heavy drinkers are more resistant to therapy. Patients who have failed to respond to treatment as outpatients often improve in hospital because they are no longer permitted to drink. Abstinence alone has been shown to induce remission.i but restarting drinking is associated with relapse. We concur that there is no difference in the severity of disease between drinkers and nondrinkers,' but have observed that the nature of the disease may be distinctive in alcohol abusers. It tends to be either inflamed and predominantly localized to the flexures or hyperkeratotic and confined to the acral areas.I These patterns are sufficiently striking to suggest the possibility of alcohol abuse to the trained observer. There is also a strong resemblance to the morp hology of psoriasis see n in association wit h AIDS, which may suggest that it is the immunosuppressive properties of alcohol that are central to the development of psoriasis in alcohol abusers. Although the effect of alcohol appears to be most marked in psoriasis, we have also found that alcohol may be responsible for treatment failure in other skin diseases (e.g., acne' and discoid eczema I) . We strongly advise the inclusion of a full alcohol history in the assessment of any patient with psoriasis and suggest that reducing ethanol consumption renders the disease more amenable to standard treatment regimens.
Elisabeth M. Higgins, MA, MRCP A. W. P. du ViVier, MD, FRCP Department of Dermatology Kings College Hospital Denmark Hill London SE5 9RS, United Kingdom REFERENCES
1. Higgins EM, du VivierA WP. Alcoholand the skin. Alcohol Alcohol 1992;27 :592- 602. 2. Vincenti GE, Blunden SM . Psoriasisand alcoholabuse. J R Army Med Corps 1987;133:77-8. 3. Higgins EM , du Vivier AWP. Cutaneous diseaseand alcohol abuse. Br Med Bull ( In press.)
4. 5.
6.
7.
hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide.Proc Nat! Acad Sci USA 1990;87:1620-4. Weiss G, Fuchs D, Hausen A, et al. Neopterin modulates toxicity mediated by reactive oxygen and chloride species. FEBS Lett 1993;321:89-92. Bulpitt KJ, Clements PJ, Lachenbruch AP, et al. Early undifferentiated connective tissue disease. Ill. Outcome and prognostic indicators in early scleroderma. Ann Intern Moo 1993;118:602-9. Wachter H, Fuchs D, Hausen A, et at Neopterin as a marker for activation of cellular immunity: immunologic basis and clinical application. Adv Clin Chern 1989;27:81141. Werner-Felmayer G, Werner ER, Fuchs 0, et al. Neopterin formation and tryptophan degradation by a human myelomonocytic cell line (THP-l) upon cytokine treatment. Cancer Res 1990;50:2863-7.
The annual cost of psoriasis To the Editor: An article recently published in this JOUR"The Annual Cost of Psoriasis" (J AM ACAD DERMATOL 1993;28:422-5), attempted to address the need for comparative costs of psoriasis therapy. The article attracted our attention because psoriasis affects up to 2%of the U.S. population! and because its authors concluded that no treatment is universally superior although one, cyclosporine, is at least twice as costly. We reviewed this article to gain an understanding of the methodology used to arrive at this conclusion. The study, performed at the Baylor Psoriasis Center in Dallas, consisted of a retrospective analysis of 66 patients treated for psoriasis between 1983 and 1991. Comparators included three types of phototherapy (Goeckerman, PUVA, and outpatient UVB) and systemic treatment (methotrexate, etretinate, hydroxyurea, and cyclosporine). A chart review was performed, and patients were included if they met the criteria of monotherapy management and availability of the patient for follow-up for up to 1 year. Data from this review were used as the clinical input for a comparative cost analysis. Retrospective pharmacoeconomic evaluation has been demonstrated to be an effective method to evaluate the cost-effectiveness of drugs. Pharmacoeconomic studies have no "economic end points," but, rather, pharmacoeconomics is the valuing of clinical outcomes. As such, there are two principal choices for clinical inputs for a pharmacoeconomic study: (I) meta-analysis of the available clinical data and (2) chart reviews.Depending on the therapy under study, either one of these methods may be advantageous. Meta-analysis provides a rigorous method for evaluating clinical success rates, failure rates, relapse rates, and side-effect profiles through statistical techniques that combine results across studies. Depending on the field under study, these mayor may not represent the real world and should always be reviewed by expert clinicians for accuracy and applicability. Chart reviewsprovide real NAL,
Correspondence 1047 world data from completed cases, but to extrapolate these data to a population broader than just one institution or ward, a large sample size is required. The sample must be large enough to account for demographic issues as well as regional and even philosophical variations in the provision of medical care and its outcomes. We thus found it distressing that the Baylor study used only 66 charts in total, with as few as six charts being used for the cyclosporine evaluation. This small sample size cannot provide a real-world evaluation of the delivery of psoriasis therapy. Because selection criteria included management with monotherapy only, other choices were not considered. Moreover, the analysis did not consider clinical efficacy, but compared regimens as if they were all equal with regard to outcomes-in fact, assuming 100% effectiveness. Again, in the real world, products are not 100% effective. These observations and their implications render the Baylor study invalid. Study inclusion criteria included patients taking cyclosporine who, according to the authors, had a more recalcitrant form of psoriasis that was refractory to other therapies. Thus the study groups are not comparable, casting serious doubt on the validity of the findings. To properly evaluate the cost-effectiveness of a drug product, it is necessary to construct a decision analytic model that accounts for each therapeutic outcome (e.g., successful therapy with no relapse, successful therapy with subsequent relapse, failed therapy treated with a backup drug). In the case of psoriasis, at least eight such outcomes are possible, and each must be evaluated in terms of probability of occurrence and cost of outcome. The sum of these eight outcomes provides the overall cost of therapy with a drug. This type of full analysis can be accomplished through a chart review, but a significantly larger sample size is necessary. One would expect the average clinical trial to examine a minimum of 25 to 30 patients in each comparator group under study. If this basic principle were to be followed in a chart review, in which a significant amount of variation will exist among patient data, a sample size of at least 10 times that used in the Baylor study is necessary. Although the Baylor study uses the terms "cost-effective" and "cost-effectiveness" throughout the Discussion and Conclusions sections, it is not a cost-effectiveness analysis. Cost-effectiveness analysis provides real world pharmacoeconomic data by considering cost of therapy with overall effectiveness. The Baylor study is a comparative cost study. The study should not be used in making formulary decisions because it identifies costs without analyzing outcomes. Such analyses can be misleading to a decision maker because consideration of outcomes often leads to a change in rank order of comparators.
Steven R. Arikian, HID Thomas R. Einarson, PhD Faculty of Pharmacy University of Toronto
Journal of the American Academy of Dermatology June 1994
1048 Correspondence REFERENCE
I. Farber EM, Nall L. Psoriasis: a reviewof recent advances in treatment. Drugs 1984;28:324-46.
Reply To the Editor: One of the purposes of our publication was to generate discussion about the cost of psoriasis therapy and the role the cost of therapy should have in selection of a particular therapeutic modality. We therefore welcome criticism of our publication, either positive or negative. We agree that the ideal cost-effective study relating to psoriasis has not been performed; however, such a study is currently under way with appropriate statistical analyses from multiple centers. We still consider our study results worthwhile because of the following: 1. Effectiveness data were compared and were similar to previously published literature reports. 2. The cost data would likely be unchanged, even if the sample size were larger. For example, with cyclosporine, the cost of medication alone is almost four times higher than any other psoriasis medication. At a fixed dosage, the mean patient drug cost would not change if cyclosporine was used for the mildest cases of psoriasis, or if the sample size were 600 rather than 6 patients. Our cost data reflect a "best case scenario"; that is, the patients tolerated the medication wel1 enough to allow a l-year period of therapy and observation. We fully realize that other factors contributing to the cost of treatment were not included, such as the cost ofcare for complications related to therapy (worst case scenarios), such as the need for liver transplantation for liver failure after methotrexate therapy. We look forward to being able to publish future costcomparative and cost-effectiveness studies for psoriasis therapy and hope that this will also stimulate similar studies in other areas of dermatology. Hans M . Sander, .MD Austin Regional Clinic Austin, TX 78731 Alan Menter, MD Baylor University Medical Center Dallas, TX 75246
Alcohol abuse and treatment resistance in skin disease To the Editor: We were interested to read the report by Gupta et aI. on alcohol intake and its relation to treatment
response in psoriasis (J AM ACAD DERMATOL 1993; 28:730-2). We have also been studying the relation between alcohol and psoriasis and have found a much higher level of alcohol abuse in patients with psoriasis than in controls. We conclude that alcohol is a risk factor for the development of psoriasis in both men and women. I Like Gupta et aI., we have noted that heavy drinkers are more resistant to therapy. Patients who have failed to respond to treatment as outpatients often improve in hospital because they are no longer permitted to drink. Abstinence alone has been shown to induce remission.i but restarting drinking is associated with relapse. We concur that there is no difference in the severity of disease between drinkers and nondrinkers,' but have observed that the nature of the disease may be distinctive in alcohol abusers. It tends to be either inflamed and predominantly localized to the flexures or hyperkeratotic and confined to the acral areas.I These patterns are sufficiently striking to suggest the possibility of alcohol abuse to the trained observer. There is also a strong resemblance to the morp hology of psoriasis see n in association wit h AIDS, which may suggest that it is the immunosuppressive properties of alcohol that are central to the development of psoriasis in alcohol abusers. Although the effect of alcohol appears to be most marked in psoriasis, we have also found that alcohol may be responsible for treatment failure in other skin diseases (e.g., acne' and discoid eczema I) . We strongly advise the inclusion of a full alcohol history in the assessment of any patient with psoriasis and suggest that reducing ethanol consumption renders the disease more amenable to standard treatment regimens.
Elisabeth M. Higgins, MA, MRCP A. W. P. du ViVier, MD, FRCP Department of Dermatology Kings College Hospital Denmark Hill London SE5 9RS, United Kingdom REFERENCES
1. Higgins EM, du VivierA WP. Alcoholand the skin. Alcohol Alcohol 1992;27 :592- 602. 2. Vincenti GE, Blunden SM . Psoriasisand alcoholabuse. J R Army Med Corps 1987;133:77-8. 3. Higgins EM , du Vivier AWP. Cutaneous diseaseand alcohol abuse. Br Med Bull ( In press.)