Drug Samples in Dermatology: Out of the Closet, Into the Dustbin

Kenneth A. Katz; Erika E. Reid; Mary-Margaret Chren

doi:10.1001/jamadermatol.2013.9711

Editorial

May 2014

Drug Samples in Dermatology: Out of the Closet, Into the Dustbin

Kenneth A. Katz, MD, MSc, MSCE¹; Erika E. Reid, MD²; Mary-Margaret Chren, MD^3,4

Author Affiliations Article Information

¹Department of Dermatology, The Permanente Medical Group Inc, Pleasanton, California
²Department of Dermatology, University of Pennsylvania, Philadelphia
³Department of Dermatology, University of California, San Francisco
⁴San Francisco Veterans Affairs Medical Center, San Francisco, California

JAMA Dermatol. 2014;150(5):483-485. doi:10.1001/jamadermatol.2013.9711

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Is drug sampling—when physicians give samples of prescription medicines provided by pharmaceutical companies to their patients—good or bad? Is the answer different for dermatologists than it is for other physicians?

Many dermatologists have already answered those questions: “bad” and “no.” Numerous institutions have banned or sharply restricted drug sampling, including the Veterans Health Administration, the US military, many universities, and Kaiser Permanente. Many private clinics have done so as well. Other organizations, including the Association of American Medical Colleges, the American Society of Health-System Pharmacists, the Institute of Medicine, and the Joint Commission, have also recommended curtailing and/or controlling drug sampling. But those questions linger in other medical settings, including many private practices not subject to institutional antisampling policies.

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June 18, 2014

Not time to throw out the samples yet

Steven R. Feldman, MD, PhD, Alan B. Fleischer, Jr, MD | Department of Dermatology, Wake Forest University School of Medicine

1. While adapaline and benzoyl peroxide are available individually as generic products, there is no generic adapaline-benzoyl peroxide combination product. 2 separate agents are not equivalent to a single product that includes both agents.12. Acne guidelines support using two drugs, a topical retinoid and a topical benzoyl peroxide.2 The academic center’s practice of prescribing them as two separate agents is not a clearly better gold standard. Giving separate drugs may be better for some patients but worse for others. Showing that samples correlates with use of a combination product for samples is not evidence that sampling is bad.3. Do we have evidence that pharmacists are providing critically important input to patients with respect to topical acne or other dermatologic therapy? Even if pharmacists are counseling our patients, sampling does not circumvent the pharmacist when the prescription is filled. Moreover, for the needy patients who do get a full course of therapy in the form of samples, they otherwise would not have had the benefit of the medication at all, much less the involvement of a pharmacist in their choice of treatment. 4. The black box lymphoma warning for topical calcineurin inhibitors that appeared after the products’ launch doesn’t tell us that new medications are bad, as the data do not support an increased risk of lymphoma with topical calcineurin inhibitors.3-5 On the contrary, topical calcineurin inhibitors are safer than topical corticosteroids, have lower oncogenic risk, and are not associated with the atrophy, telangiectasias, and even potential HPA axis suppression associated with topical corticosteroids. Topical calcineurin inhibitors can cause stinging, so letting the patient try a sample of them before purchasing them is particularly helpful.5. A controlled trial found that having acne patients sample treatment at the office visit may increase adherence to that treatment. 6 The suggestion that sampling’s benefits can be achieved with Crisco is not yet supported by evidence. A major barrier to adherence is fear,7 and applying Crisco to patients may not get them past the fear of applying a drug. Moreover, many products can’t be demonstrated adequately using Crisco, including foams, sprays, shampoo, and tape formulations. Moreover, the sample of Crisco will not show patients if the medication is tolerable for them; patients who may have discovered intolerability had they had a sample may, in a sample-free world, end up buying expensive medications that they cannot use.6. The desire to see patients get the best care at the lowest cost is good, but the available evidence does not support the idea that emptying the closet of samples promotes cost-effectiveness. Sampling may drive some prescribing behavior in dermatology (so far, only association has been demonstrated), but it may be that sampling encourages use of better drugs. Even if samples sometimes encourage the use of a less than ideal treatment, it may be that a better solution would be to add samples of generic medications to our sample closets rather than losing the benefits of the samples we currently have.1. Yentzer BA, Ade RA, Fountain JM, Clark AR, Taylor SL, Fleischer AB Jr, Feldman SR. Simplifying regimens promotes greater adherence and outcomes with topical acne medications: a randomized controlled trial. Cutis. 2010 Aug;86(2):103-8. 2. Nast A, Dréno B, Bettoli V, Degitz K, Erdmann R, Finlay AY, Ganceviciene R, Haedersdal M, Layton A, López-Estebaranz JL, Ochsendorf F, Oprica C, Rosumeck S, Rzany B, Sammain A, Simonart T, Veien NK, Zivković MV, Zouboulis CC, Gollnick H; European Dermatology Forum. European evidence-based (S3) guidelines for the treatment of acne. J Eur Acad Dermatol Venereol. 2012 Feb;26 Suppl 1:1-29. 3. Margolis DJ, Hoffstad O, Bilker W. Lack of association between exposure to topical calcineurin inhibitors and skin cancer in adults. Dermatology. 2007;214(4):289-95.4. Tennis P, Gelfand JM, Rothman KJ. Evaluation of cancer risk related to atopic dermatitis and use of topical calcineurin inhibitors. Br J Dermatol. 2011 Sep;165(3):465-73. 5. Arellano FM, Wentworth CE, Arana A, Fernández C, Paul CF. Risk of lymphoma following exposure to calcineurin inhibitors and topical steroids in patients with atopic dermatitis. J Invest Dermatol. 2007 Apr;127(4):808-16. 6. Sandoval LF, Semble A, Gustafson CJ, Huang KE, Levender MM, Feldman SR. Pilot randomized-control trial to assess the effect product sampling has on adherence using adapalene/benzoyl peroxide gel in acne patients. J Drugs Dermatol. 2014 Feb;13(2):135-40. 7. Brown KK, Rehmus WE, Kimball AB. Determining the relative importance of patient motivations for nonadherence to topical corticosteroid therapy in psoriasis. J Am Acad Dermatol. 2006 Oct;55(4):607-13.

CONFLICT OF INTEREST: No specific funding for this work.Fleischer:Investigator (Grants to instititution): Regeneron, Abbvie, Eli Lilly, GaldermaConsultant (honoraria): Galderma, CelgeneEmployment (salary): MerzFeldmanGalderma, GSK/Stiefel, Leo Pharma, Celgene, Pfizer, Valeant, Abbott, Amgen, Astellas, Janssen, Lilly, Merz, Novartis, Taro, National Biological Corporation, and National Psoriasis Foundation. I am founder and majority owner of www.DrScore.com. I am a founder and part owner of Causa Research, a company dedicated to enhancing patients’ adherence to treatment.

August 5, 2014

Reply to “Not time to throw out the samples yet”

Kenneth A. Katz, MD, MSc, MSCE | Department of Dermatology, The Permanente Medical Group Inc, 7601 Stoneridge Dr, South Building, Second Floor, Pleasanton, CA 94588

In arguing against our commentary[1] and in favor of physician use of drug samples, Feldman and Fleischer[2] present a panoply of theories about ways in which drug samples might benefit — or might not harm — patients. Lacking from their argument, however, is evidence. Indeed, measured against the growing body of data demonstrating that drug samples actually harm patients — by leading to prescribing of medicines that are more expensive[3-6], less appropriate[7, 8], and less safely dispensed[7] — Feldman and Fleischer’s conjectures are not convincing. First, Feldman and Fleischer advance a “might-benefit” argument. Feldman and Fleischer hypothesize that that a combination acne product, for which generic substitutes are not available, might be superior for some patients. They present no actual evidence that the combination product is in fact superior to its two constituent products prescribed individually. But even if the combination product were superior, Feldman and Fleischer present no actual evidence that obtaining better outcomes would hinge on the use of samples. Let’s give our dermatologist colleagues the benefit of the doubt: if data actually showed that the combination product were superior to its two constituent products prescribed individually, dermatologists interested in evidence-based practice would likely prescribe it (at least to patients who could afford it), regardless of whether samples were available. Second is a “might-not-harm” contention. Feldman and Fleischer hypothesize that pharmacist involvement might not be critical for “topical acne or other dermatologic therapy.” This argument implicitly acknowledges the benefits of pharmacist involvement in non-dermatologic prescribing. Why should dermatology differ? Pharmacist involvement can increase adherence[9] and correct prescribing errors[10]. And physicians generally recognize the value that pharmacists can potentially add. In one survey, for example, 60% of physician respondents agreed that patients receiving drug samples miss out on important counseling by pharmacists regarding action after missing a dose, storing medicines properly, and avoiding drug interactions.[11] In another survey, 85% of physician respondents believed that physician distribution of samples deprived patients of pharmacists’ involvement in identifying drug interactions and counseling on appropriate use and potential adverse drug effects.[12] Third: another “might-not-harm” argument. Feldman and Fleischer cite evidence supporting the safety of topical calcineurin inhibitors. That misses the larger point, which is that newer drugs — the type that tend to be most heavily sampled (remember rofecoxib [Vioxx]?) — have evolving safety profiles that make them, overall, less safe than older drugs.[13] There is, simply, less drug safety in the sample closet than out of it. As for Feldman and Fleischer’s contention regarding a “particular” benefit of sampling topical calcineurin inhibitors: show us the evidence that such sampling – compared with, say, a conversation about the expected symptoms – actually leads to improved outcomes. Fourth: back to a “might-help” assertion. Feldman and Fleischer state that a controlled trial[14] showed that sampling “may increase adherence” to an acne treatment. Data from the referenced trial, however, do not support that claim. The trial failed to show a statistically significant difference in median adherence rates — the trial’s primary outcome — in the sample group (50%) compared with the no-sample group (35%) (p=0.67).[14] Granted, the trial was small, with only 17 participants.[14] But small numbers should not obfuscate the fact that the trial failed to show that samples actually affected adherence rates.Fifth is another “might-benefit” claim. Feldman and Fleischer allege that drug samples trump Crisco in helping patients overcome a fear of topical medicines that undermines medication adherence. Again, Feldman and Fleischer do not cite actual data showing that drug samples can allay patient fears and promote medication adherence. In fact, the study Feldman and Fleischer cite[15] did not actually investigate drug samples at all. Rather, the study investigated patient motivations for nonadherence to topical corticosteroids. What worked to overcome nonadherence, the study found, was instructing patients on the appropriate use of the medicine. Moreover, another study demonstrated that cost-related nonadherence, in fact, is strongly related to accessing drug samples.[16]Sixth: another “might benefit” argument. Feldman and Fleischer speculate that patients in a sample-free world might ultimately buy expensive medicines they cannot tolerate. That might occur in some cases. But on balance, drug samples negatively impact the finances of patients and the health-care system overall. What Hurley et al.[4] showed in dermatology — that physicians who distribute samples are more likely to prescribe drugs with higher price tags — has been observed in family practice.[17] Residents with access to drug samples, another study found, were less likely to choose unadvertised drugs and over-the-counter drugs than those who did not have access to samples.[6] And at a large university-affiliated internal medicine practice, yet another study showed, generic medications accounted for 30 percent of prescriptions after drug samples were banned, compared with 12 percent before the ban.[3] Furthermore, drug samples can in fact lead patients to buy expensive medicines they cannot use; Medicare beneficiaries receiving drug samples had lower medication adherence than those not receiving drug samples.[16]Seventh: another in the “might benefit” column: an argument that “needy patients” may get a full course of therapy when they “otherwise would not have had the benefit of the medication at all.”[2] Again, that might be the case for some patients. But evidence shows that most samples do not help those most in need. Analyzing data on 32,681 US residents from the 2003 Medical Expenditure Panel Survey, Cutrona et al. demonstrated that persons with health insurance were significantly more likely to receive a drug sample than persons without insurance.[18] Furthermore, the poorest third of respondents in that survey were less likely to receive drug samples than those with incomes at 400% of the federal poverty level or higher.[18] Very similar findings were demonstrated in a pediatric cohort of 10,295 US residents.[19] Among Medicare beneficiaries, African-Americans and Hispanics were less likely than whites to receive samples.[16] Teichman coined the phrase “nobility myth” to describe physicians’ mistaken beliefs that they use samples for uninsured and indigent populations despite evidence to the contrary.[20]Finally, a “might-benefit” argument. Feldman and Fleischer hypothesize that adding samples of generic drugs might be more beneficial than jettisoning the entire practice of drug sampling. We await the study that tests Feldman and Fleischer’s hypothesis. We also await the emergence of a business model in generic drug manufacturing that would support such widespread sampling. There is nothing stopping generic drug manufacturers today from doing that today. As medicine continues to move toward evidence-based practice, dermatologists’ approach to samples should be guided by evidence — not by theory, hypothesis, conjecture, or wishful thinking. The actual evidence regarding drug samples shows that it fails to benefit and actually harms our patients and our healthcare system. Colleagues, empty your closets. References1. Katz KA, Reid EE, Chren MM. Drug samples in dermatology: out of the closet, into the dustbin. JAMA Dermatol 2014 May;150(5):483-5.2. Feldman SR F, AB Jr. . No time to throw out the samples yet. Available at: http://archderm.jamanetwork.com/article.aspx?articleid=1860844&resultClick=3. Accessed 7/2/14.3. Miller DP, Mansfield RJ, Woods JB, Wofford JL, Moran WP. The impact of drug samples on prescribing to the uninsured. South Med J 2008 Sep;101(9):888-93.4. Hurley MP, Stafford RS, Lane AT. Characterizing the relationship between free drug samples and prescription patterns for acne vulgaris and rosacea. JAMA Dermatol 2014 May;150(5):487-93.5. Alexander GC, Zhang J, Basu A. Characteristics of patients receiving pharmaceutical samples and association between sample receipt and out-of-pocket prescription costs. Med Care 2008 Apr;46(4):394-402.6. Adair RF, Holmgren LR. Do drug samples influence resident prescribing behavior? A randomized trial. Am J Med 2005 Aug;118(8):881-4.7. Chimonas S, Kassirer JP. No more free drug samples? PLoS Med 2009 May 5;6(5):e1000074.8. Boltri JM, Gordon ER, Vogel RL. Effect of antihypertensive samples on physician prescribing patterns. Fam Med 2002 Nov-Dec;34(10):729-31.9. Mino-Leon D, Reyes-Morales H, Flores-Hernandez S. Effectiveness of involving pharmacists in the process of ambulatory health care to improve drug treatment adherence and disease control. J Eval Clin Pract 2014 Jun 21.10. Stasiak P, Afilalo M, Castelino T, et al. Detection and correction of prescription errors by an emergency department pharmacy service. CJEM 2014 May 1;16(3):193-206.11. Aseeri MA, Miller DR. Patient education and counseling for drug samples dispensed at physicians' offices. J Am Pharm Assoc (2003) 2006 Sep-Oct;46(5):621-3.12. Chew LD, O'Young TS, Hazlet TK, Bradley KA, Maynard C, Lessler DS. A physician survey of the effect of drug sample availability on physicians' behavior. J Gen Intern Med 2000 Jul;15(7):478-83.13. Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH. Timing of new black box warnings and withdrawals for prescription medications. JAMA 2002 May 1;287(17):2215-20.14. Sandoval LF, Semble A, Gustafson CJ, Huang KE, Levender MM, Feldman SR. Pilot randomized-control trial to assess the effect product sampling has on adherence using adapalene/benzoyl peroxide gel in acne patients. J Drugs Dermatol 2014 Feb;13(2):135-40.15. Brown KK, Rehmus WE, Kimball AB. Determining the relative importance of patient motivations for nonadherence to topical corticosteroid therapy in psoriasis. J Am Acad Dermatol 2006 Oct;55(4):607-13.16. Tjia J, Briesacher BA, Soumerai SB, et al. Medicare beneficiaries and free prescription drug samples: a national survey. J Gen Intern Med 2008 Jun;23(6):709-14.17. Symm B, Averitt M, Forjuoh SN, Preece C. Effects of using free sample medications on the prescribing practices of family physicians. J Am Board Fam Med 2006 Sep-Oct;19(5):443-9.18. Cutrona SL, Woolhandler S, Lasser KE, Bor DH, McCormick D, Himmelstein DU. Characteristics of recipients of free prescription drug samples: a nationally representative analysis. Am J Public Health 2008 Feb;98(2):284-9.19. Cutrona SL, Woolhandler S, Lasser KE, et al. Free drug samples in the United States: characteristics of pediatric recipients and safety concerns. Pediatrics 2008 Oct;122(4):736-42.20. Teichman PG, Caffee AE. Pharmaceutical starter samples. J Am Board Fam Pract 2002 Nov-Dec;15(6):509-10.

CONFLICT OF INTEREST: Conflict of Interest Disclosures: Dr. Katz is a shareholder in Synta Pharmaceuticals Corp. and Arrowhead Research Corp. Dr. Reid has no conflicts. Dr. Chren serves as a consultant to Genentech. Funding for Dr. Chren in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (K24 AR052667).

Drug Samples in Dermatology: Out of the Closet, Into the Dustbin

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