w wz 16«2y Kor. J. Clin. Pharm., Vol. 16, No. 2. 2006 w t w BÁ½ C B w w w C x sƒ Analysis of Perception on the Bioequivalence-assured Generic Drugs Eui Kyung Lee a G and Dong Sook Kim b a Graduate School of Clinical Pharmacy, Sookmyung Women's University, Seoul, Korea b Department of Research, Health Insurance Review Agency, Seoul, Korea Objectives: Bio-equivalence(BE) test is important not only to ensure the quality of generic drugs, but also to promote drug substitution under the separation of prescribing and dispensing practice(spd). This study was intended to investigate the perception of consumers, doctors, and pharmacists on the confidence of bio-equivalence(be) assured drugs. Methods: Nation-wide telephone interview survey was conducted for 1,018 consumers, 800 doctors, and 806 pharmacists from September to October in 2003. Descriptive analysis and χ 2 analysis were conducted. Results: Even though people showed higher confidence level for the Bioequivalent drugs compared with Bio-inequivalent drugs, the confidence was generally low. Among those asked about the therapeutic substitutability of original drugs by BE versions, 95.78% of pharmacists responded positive, while only 39.33% of consumers and 31.13% of doctors said so. The elderly, the less educated, who takes chronic disease medicine, pays high cost of prescription drugs, and are in the low income responded less aware of that. Also most consumers got information such as effect of drugs from either media or doctors. Conclusions: In order for people to believe that BE drugs and original drugs are equivalent, we need to strengthen health education, and to clarify any misunderstanding. It is also necessary for the national policy to provide accurate information about drugs to the public. Key words - Bioequivalence test, Generic drug, Drug substitution t z Áw Á x w Á t, t px yƒ z t evw t. t w t z» 1970 p phenitoin digoxin w l. digoxin z t, š x ƒ j š, Lindenbaum 1) w t š x ƒ 7 ùkþ z t batch 4 ƒ š.» t yw z Correspondence to : w w w p q 2ƒ 53-12 w w w 307y (140-742) Tel: 02-710-9799, Fax: 02-712-9725 E-mail: ekyung@sm.ac.kr e w w, (bioavailability) s ƒw w 2). FDA 1977 l t xƒ w x w ³ wš(code of Federal Regulation: CFR Title 21 Part 320) 3-5), t ƒ yx ww w w š wš 6). ù 1989 1 1 z xƒ t w t x ƒ š w, t w w yw. t w y w t t w šw d w, q w eš 7-8). 23 2w w t t w w ( w ) ww 139
140 Kor. J. Clin. Pharm., Vol. 16, No. 2, 2006 ƒ wš zm w ³ wš w 9-10). t t ƒ w t y t y œ w t z ƒ x y» w 11-12). z šƒ t ƒwš t y ƒ t w t w x k v ƒ. ƒ t x y yw w ƒ j 13). ù ƒ w ü» w t w, ü y w» z wš. t t» ü t y w» w x z sƒ w w t? yw ww w 14-16). 2001 11 œšw t 183t ù, 2003 11 804t ƒw š z ƒ. y,» xƒ w x w ƒw š. ù w ƒ wš ù ƒ y w š 17). ù t w e w w wš 18). y wš, w» w v w» œwš, t, ƒ, Á Á w q w. ƒ z p ƒ ùkù w. w t r. t w t q w» w Á Á y w. t t w. 2003 m Á Á s š w y y w mw t 4 4,000 t w. 2003 8 31» x sƒ» w 1/8 w w t t š w w. t 8»k sww 9 t 1 w z 2 m w. te 800 ù t w w w y š w te 800 2,934 t w. 2003 8 31» x s ƒ w t w. t w, š w Á w, w w w y š w te 800 2,734 t w. Á Á w 2003 9 29 l 10 20 ¾ w, w 1,018, 800, 806. w Á Á p <t 1> š, Á Á s w. Á Á ƒ p t w w w, t w ü w. m SAS 8.2 m v w w, s³ χ 2 w w. z p w» w x ƒ z ww š, p w χ 2 w. m 5% w» w. w w Á Á r» w ƒ z ƒ t w š q w w w. w w ù ƒ w w ù, ª w ƒ mww wá w.
w t w 141 Table 1. Baseline characteristics of study population (unit: %, persons) consumers doctors pharmacists responder population 1) responder population 2) responder population 3) Ágender male 47.94 49.56 88.25 84.66 49.75 43.78 female 52.06 50.44 11.75 15.34 50.25 56.22 Áage 20~29 yrs 20.75 22.60 0.13 0.84 7.46 10.86 30~39 yrs 22.52 24.39 26.53 34.35 33.33 29.95 40~49 yrs 23.11 22.18 43.43 38.85 26.00 24.64 50~59 yrs 15.44 13.53 18.90 14.80 17.66 18.66 + 60 yrs 18.19 17.30 11.01 11.16 15.55 15.89 Áregion big city 46.07 46.71 53.88 53.31 52.73 52.97 medium city 37.52-39.25 39.86 38.59 38.60 small city 16.40 53.29 6.88 6.84 8.68 8.44 100.00 (1,018) 100.00 (34,074,474) 1) 100.00 (800) 100.00 (23,452) 2) 100.00 (806) 100.00 (19,137) 3) footnotes: 1) Department of statistics 2002 data footnotes: 2) HIRA(Health Insurance Review Agency) clinic registration data as of August 31, 2003. footnotes: 3) HIRA(Health Insurance Review Agency) pharmacy registration data as of August 31, 2003., t z, w ù w ƒ š w 39.33%, 31.13 %, 95.78% (t 2. ). t w ƒ 17.70%, 58.63%, 2.48% ùkù, w t w w ƒ š. p w š w ƒ w 42.28% w. w w 56.02% ùkû. wr x w w 17.49%, 5.38%, 70.05%ƒ w ƒ y š w, w û. Table 2. Perception of the equivalency about BE assured drugs and original drugs equivalency about BE assured generics and original drugs (unit: %, (persons) equivalency about BE un-assured generics and original drugs consumers equivalent/ substitutable 39.33 65.72* 17.49 35.33* inequivalent/ unsubstitutable 17.70 33.10* 35.07 62.82* others 0.69 1.16* 0.88 1.85* not knowing 42.28-46.56 - total 100.00 (1,017) 100.00* (587) 100.00 (1,018) doctors equivalent/ substitutable 31.13 5.38 inequivalent/ unsubstitutable 58.63 88.63 others 10.25 6.00 total 100.00(800) 100.00(800) pharmacists equivalent/ substitutable 95.78 60.05 inequivalent/ unsubstitutable 2.48 35.36 others 1.74 4.59 total 100.00(805) 100.00(806) footnotes) *: results without the responders who answered not knowing 100.00* (544)
142 Kor. J. Clin. Pharm., Vol. 16, No. 2, 2006 zw p w 1. ú t w zw p t w ƒ ùkù r» w chi-square w. w ùkû 5% m w ùkû (t 3. ). ûš û w ùkû (p<.001). w w w ƒ û ùkû (p<.001). û w ù ƒ ùkû m w. 2. ú t w ú t w z p w, 40 w 13.83%, 60 13.64%, 20Á30 7.98% w š w (t 4. ). p ƒ 60 d 57.06%~64.32%, 60 40.91% û ùkûš m w. ù t m w. 3. ú t w ú z p r, w û, š ƒ ùkû w m w (t 5. ). w š w û ƒ 69.25% 57.78% w š, 60 77.60%ƒ w š w û 66.90%~59.33% w š w û. wr w s³ 50 ú w š w 71.94% ƒ, ƒ w Table 3. Consumers' perception of the equivalency about BE assured generics and original drugs by socio-eonomic characteristics equivalent/ substitutable inequivalent/ unsubstitutable others not knowing total p-value total 39.33 17.70 0.69 42.28 100.00(1,017) ½ gender male 40.04 19.92 0.41 39.63 100.00( 487) 0.1499 female 38.68 15.66 0.94 44.72 100.00( 530) ½ age 20-39 yrs 50.16 19.94 0.32 29.58 100.00( 311) <.0001 40-49 yrs 42.86 20.60 1.10 35.44 100.00( 364) 50-59 ys 32.21 12.98 0.48 54.33 100.00( 208) + 60 15.67 11.94 0.75 71.64 100.00( 134) ½ income (won) ~1,000,000 18.72 15.32 0.85 65.11 100.00( 235) <.0001 1,000,000~2,000,000 42.74 18.23 0.57 38.46 100.00( 351) + 2,000,000 47.78 18.74 0.70 32.79 100.00( 427) ½ education level ~middle school 22.22 13.19 0.69 63.89 100.00( 288) <.0001 high school 39.04 20.22 0.56 40.17 100.00( 356) + college 53.41 18.53 0.82 27.25 100.00( 367) ½ taking medicines chronically taking 24.28 16.76 0.00 58.96 100.00( 173) <.0001 not taking 42.42 17.89 0.83 38.86 100.00( 844)
w t w 143 Table 4. Physicians' perception of the equivalency about BE assured generics and original drugs by socio-eonomic characteristics equivalent inequivalent but substitutable inequivalent and unsubstitutable others total p-value total 11.63 19.50 58.63 10.25 100(800) ½ gender male 12.18 19.41 58.78 9.63 100(706) 0.2732 female 7.45 20.21 57.45 14.89 100( 94) ½ age 20-39 yrs 7.98 18.78 64.32 8.92 100(213) 0.0033 40-49 yrs 13.83 18.73 57.06 10.37 100(347) 50-59 ys 10.60 19.21 64.24 5.96 100(151) + 60 13.64 25.00 40.91 20.45 100( 88) ½ specialty general practitioner 11.90 28.57 53.57 5.95 100(168) 0.1179 internal medicine 15.89 21.50 53.27 9.35 100(107) pediatrics 7.95 17.05 68.18 6.82 100( 88) O & G 7.46 13.43 65.67 13.43 100( 67) surgery 18.00 6.00 60.00 16.00 100( 50) otorhinolaryngology 10.87 6.52 67.39 15.22 100( 46) orthopedic 13.16 13.16 60.53 13.16 100( 38) home-doctoring 22.86 20.00 48.57 8.57 100( 35) urology 8.57 25.71 60.00 5.71 100( 35) ophthalmology 11.43 14.29 62.86 11.43 100( 35) others* 7.53 10.26 68.80 13.41 100(131) footnotes) *: dermatology, psychiatry, neurology, neuro-logical surgery, rehabilitation, anesthesia, neuropsychiatry, the department of radiology, chest surgery ƒ û ùkû w m w (t 5. ). t w w t r» w z ƒ w w. z w ù l š w 41.85% ƒ š, l š w ƒ 22.40% w (t 6 ). ƒ w l 38.11% ƒ 35.27% w. z w»k,, x š ƒ w»k, x,. t t w ƒ ùkû m w (t 7. ). z l 52.04%ƒ t ƒ w w š w w, l w ƒ š 34.80%, l 31.43% û. w ƒ w 39.53%ƒ ƒ w w š w ù l 21.74% û w (p< 0.0001). wr z w š w 65.41%, ƒ w š w 52.09%ƒ t w š w, t w z œw ƒ v w wš. š w e t w y w t w jš w ª t y w. 2001 8 t y ƒ ³
144 Kor. J. Clin. Pharm., Vol. 16, No. 2, 2006 Table 5. Pharmacists' perception of the equivalency about BE assured generics and original drugs by socio-eonomic characteristics equivalent inequivalent but substitutable inequivalent and unsubstitutable others total p-value total 63.48 32.30 2.48 1.74 100.00(800) ½ gender male 69.25 28.00 1.50 1.25 100.00(400) 0.0048 female 57.78 36.54 3.46 2.22 100.00(405) ½ age 20-39 yrs 59.33 36.39 2.75 1.53 100.00(327) 0.0056 40-49 yrs 59.33 37.80 1.91 0.96 100.00(209) 50-59 ys 66.90 26.06 4.23 2.82 100.00(142) + 60 77.60 19.20 0.80 2.40 100.00(125) ½ average number of dispensing per day ~50 71.94 24.84 1.61 1.61 100.00(310) 0.0003 50~99 61.56 33.63 2.40 2.40 100.00(333) + 100 50.93 44.10 4.35 0.62 100.00(161) Table 6. Consumers' Information sources for effects and price of drugs information sources effects of drugs price of drugs doctors 22.40 3.54 pharmacists 9.63 38.11 mass media 41.85 13.16 internet 3.44 2.26 others 9.63 7.66 none 13.06 35.27 total 100.00(1,018) 100.00(1,018) yw d t w d t yw t t w w j»ƒ. ù w t w w» wš ù w û ùkû. wš t w ù w ƒ š w 95.78% wù ù ƒƒ 39.33%, 31.13% w. e Table 7. Consumers' perception of the equivalency about BE assured generics and original drugs by information sources information sources equivalent/ substitutable inequivalent/ unsubstitutable others not knowing total p-value total 39.33 17.70 0.69 42.28 100.00(1,017) ½ effect of drugs doctors 34.80 20.26 0.44 44.49 100.00( 227) <0.0001 pharmacists 52.04 13.27 0.00 34.69 100.00( 98) mass media 44.60 17.84 0.94 36.62 100.00( 426) internet 31.43 31.43 2.86 34.29 100.00( 35) others 36.73 21.43 1.02 40.82 100.00( 98) none 24.81 9.77 0.00 65.41 100.00( 133) ½ price of drugs doctors 30.56 25.00 5.56 38.89 100.00( 36) <0.0001 pharmacists 46.51 17.05 0.26 36.18 100.00( 387) mass media 40.30 25.37 0.00 34.33 100.00( 134) internet 26.09 26.09 8.70 39.13 100.00( 23) others 35.90 17.95 2.56 43.59 100.00( 78) none 33.70 14.21 0.00 52.09 100.00( 359)
w t w 145 w 17.49%, 5.38%, 60.05% w r. w w w ƒ» wù, û š w. ƒ (National Consumers League; NCL, 1999) 19) 1999 1,000 w y, 57% t t w š š w, 83%ƒ t t, z ƒ wš ƒ w t w ùkû w š w. t ƒ j, w» d d w wš t t w j» w»,?? wš w j» w z v w., w œw yw v ƒ. w w w q w 42.28% š t w œ v w. w t w wš, t w š ö û r š, e w w wš. ù w, d, w, ƒ ûš, ƒ û û w Áy y yw v ƒ., t w z œw w w. l y w y w v ƒ. l t w w l l ƒ û ùkù, l mw ü w m yw œ v w. 2002 t y w $400,000 w w, w Ÿš s l,, Ÿš, p y wš ù w v ƒ., š p w œw, w w v ƒ. t wš t t ƒ w, 31.13% ƒ û. t w œw ƒ w w. y wš v w ew, y w œwš y yw w. w d t t t w y w, xƒ w y»z wš, w, mw y yw v ƒ. l, p w ü s w j w?œ, w w. w w œw w yw v ƒ., t w y w z œ x wš w w w w. x, w w. w x ù w. w œ t œ w m wš, w w w w jš v w. w n ywš, w y w, ù ƒ t y, x t, x ƒ w z ƒ. š x 1. Lindenbaum J., Mellow MH, Blackstone MO, Butler VP, Variation in biologic availability of digoxin from four preparations N Eng H Med 1971; 285: 1344-1347. 2. Á»yÁ Á½, Õ w x» üxyö, wz Ø, 1999, 29«3y, pp.247-251. 3. FDA, Guidance for Industry: Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System, 2000 Aug. 4. FDA, Guidance for Industry: Bioavailability and Bioequiv-
146 Kor. J. Clin. Pharm., Vol. 16, No. 2, 2006 alence Studies for orally Administered Drug Products-General Considerations, 2002 Jul. 5. FDA, Approved Drug Products, 23rd edition, 2003. 6., w x Ø, t Ø, 4«1y, 1996, pp77-82. 7. Guberman A, Corman C, Generic substitution for brand name antiepileptic drugs: a survey, Can J Neurol Sci, 27(1), 2000 Feb, pp37-43. 8. Darryl SR, Experience with a two-tired therapeutic interchange policy, American Journal of Hospital Pharmacy, 46, 1989 Sep, pp1792-1798. 9. ½, Ø, wø, 7«, 1999, pp16-21. 10. Á,» w w, w z, 2001. 11. David AM, Mott DA, Richard RC, Cline RR, Exploring generic drug use behavior: the role of prescribers and pharmacists in the opportunity for generic drug use and generic substitution, Med Care, 40(8), 2002 Aug, pp662-674. 12. Banahan, Benjamin F, Kolassa EM, A Physician Survey on Generic Drugs and Substitution of Critical Dose Medications, Archives of Internal Medicine, 157(18), 1997 Oct, pp2080-2088. 13. Michael AF, Jerry A, Economic Consequences of Underuse of Generic Drugs: Evidence from Medicaid and Implications for Medicaid and Implications for Prescription Drug Benefit Plans, Health Services Research, 38(4), 2003 Aug, pp1051-1063. 14. t t, w w z Ø, 2002. 15. t t, w xt eø, 2002. 16. t t, w w z (II)Ø, 2003. 17. Á Á½, w x w k y, w z, 2003. 18. Á Á Á x Á, sƒ w», w z, 2005. 19. National Consumers League (NCL) News, Generic Drugs Make Healthcare Costs Easier for Consumers to Swallow, 1999, Oct.