Therapeutic uses of investigational drugs: Research extension, compassionate use, and expanded access;O uso de drogas ainda experimentais em assistência: Extensão de pesquisa, uso compassivo e acesso expandido

Revista Panamericana de Salud Publica/Pan American Journal of Public Health

Volumn 23, Issue 3, 2008, Pages 198-206

  Goldim, José Roberto ^a,b  

^a HOSPITAL DE CLÍNICAS DE PORTO ALEGRE   (Brazil)

^b Laboratório de Bioética   (Brazil)

Author keywords

Brazil; Ethics committees; Investigational; ethics; Research; drugs; Research; research financing

Indexed keywords

DRUG; ETHICS; FINANCE; RESEARCH;

BRAZIL; SOUTH AMERICA;

EID: 44849119304     PISSN: 10204989     EISSN: 16805348     Source Type: Journal    
DOI: 10.1590/s1020-49892008000300007     Document Type: Article

References (77)

1. Guidance for industry. E6. Good clinical practice: Consolidated guidance. Rockville, Maryland: FDA; 1996. Disponível em: http:// www.fda.gov/cder/guidance/959fnl.pdf. Acessado em janeiro de 2008.
2. Grupo Mercado Comum (Mercosul). Boas práticas clínicas. Mercosul; 1996. Disponível em: http:// www.bioetica.ufrgs.br/bpcmerco. htm. Acessado em janeiro de 2008.
3. Mross K, Marz W. Klinische Studien: Fundament einer Evidenz-basierten Onkologie -
4. Bestandsaufnahme und Zukunft im Zeitalter des Internet. Onkologie. 2001;24(Suppl 1): 24-34.
5. Thompson L. Experimental treatments? Unapproved but not always unavailable. FDA Consumer Magazine. 2000;34(1). Disponível em: http://www.fda.gov/fdac/features/2000/100_exp.html. Acessado em janeiro de 2008.
6. Mello NK, Mendelson JH, Lukas SE, Gastfriend DR, Teoh SK, Holman BL. Buprenorphine treatment of opiate and cocaine abuse:
7. clinical and preclinical studies. Harv Rev Psychiatry. 1993;1(3):168-83.
8. Estados Unidos, Food and Drug Administration. Expanded access to investigational drugs for treatment use. Fed Reg. 2006;71 (240): 75147-68.
9. Brasil, Ministério da Saúde, Agência Nacional de Vigilância Sanitária. Resolução de Diretoria Colegiada (RDC) no. 26 de 17 de dezembro de 1999. São Paulo: ANVISA; 1999. Disponí vel em: http://www.anvisa.gov.br/legis/
10. resol/26_99rdc.htm. Acessado em janeiro de 2008.
11. Drive for drugs leads to baby clinical trials. Nature. 2006;440(7083):406-7.
12. Brasil, Ministério da Saúde, Conselho Nacional de Saúde. Resolução CNS 251/97. Normas de pesquisa com novos fármacos, medicamentos, vacinas e testes diagnósticos envolvendo seres humanos. Diário Oficial da União 1997. Brasília: Ministério da Saúde; 1997. Pp. 21117. Disponível em: http://www.datasus.gov.br/conselho/reso197/res25197.htm. Acessado em janeiro de 2008.
13. Hulley SB, Cummings SR, Browner WS, Grady D, Hearst N, Newman TB. Delineando a pesquisa clínica. Porto Alegre: Artmed; 2006.
14. Judge decides drug company not required to give experimental drug [in the news]. Professional Ethics Rep. 2005;XVIII(2). Disponí vel em: http://www.aaas.org/spp/sfrl/per/per41.htm#news. Acessado em janeiro de 2008.
15. Fialuridina. Folha de São Paulo. 1995 29/10/ 1995;Sect. 2.
16. Estados Unidos, National Institutes of Health. Glossary of clinical trials terms. Bethesda: NTH; 2006. Disponível em: http://www. clinicaltrials.gov/ct2/info/glossary. Acessado em janeiro de 2008.
17. World Medical Association. Declaração de Helsinki. Helsinki: WMA; 1964. Disponível em: http://www.wma.net/e/policy/b3.htm. Acessado em janeiro de 2008.
18. Estados Unidos, Food and Drug Administration. Charging for investigational drugs. Fed Reg. 2006;71(240):75168-81. Disponível em: http://www.epa.gov/EPA-IMPACT/2006/ December/Day-14/i9685.htm. Acessado em janeiro de 2008.
19. Estados Unidos, Food and Drug Administration. Code of Federal Regulations, title 21, volume 5 [revised as of April 1, 2007]. 21CFR312.7. Part 312 - Investigational new drug application. Disponível em: http:// www. accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.7. Acessado em janeiro de 2008.
20. Mund VA. The return on investment of the innovative pharmaceutical firm. Em: Cooper JA, editor. The economics of drug innovation. Washington: American University; 1969. Pp. 96-125.
21. Ismail F. The Doha declaration on TRIPS and public health and negotiation in the WTO on paragraph 6 - why PhRMA needs to join the consensus. J Intellectual Property. 2003;6(3): 393-402.
22. Rott P. The Doha declaration - good news for public health? Intellectual Property Quart. 2003(1 ):285-311.
23. Jonas H. Ética, medicina e técnica. Lisboa: Vega; 1994.
24. Goldim JR. O consentimento informado numa perspectiva além da autonomia. Rev AMRIGS. 2002;46(3,4):109-16.
25. Canadian Legal Information Institute [site da Internet]. Food and Drug Regulations. PART C: Drugs. Division 8: Sale of new drug for emergency treatment. Disponível em: http:// www.canlii.org/ca/regu/crc870/. Acessado em dezembro de 2007.
26. Australian government. Access to unapproved therapeutic goods via the special access scheme. Canberra: Department of Health and Ageing, Therapeutic Goods Administration: 2004. Disponível em: http://www.tga.gov. au/docs/pdf/unapproved/sas.pdf. Acessado em janeiro de 2008.
27. Europa. Community procedures for the authorisation and follow-up of medicines for human and veterinary use. Directive 2001/83/EC. JO L; 2001. Pp. 67.
28. Gayrard V, Picard-Hagen N, Viguie C, Laroute V, Andreoletti O, Toutain PL. A possible pharmacological explanation for quinacrine failure to treat prion diseases: pharmacokinetic investigations in a ovine model of scrapie. Br J Pharmacol. 2005;144(3):386-93.
29. Short MA, Schlichting D, Qualy RL. From bench to bedside: a review of the clinical trial development plan of drotrecogin alfa (activated). Curr Med Res Opin. 2006;22(12):2525-40.
30. Howell A. Pure oestrogen antagonists for the treatment of advanced breast cancer. Endocr Relat Cancer. 2006;13(3):689-706.
31. Barlesi F, Tchouhadjian C, Doddoli C, Villani P, Greillier L, Kleisbauer JP, et al. Gefitinib (ZD1839, Iressa) in non-small-cell lung cancer: a review of clinical trials from a daily practice perspective. Fundam Clin Pharmacol. 2005; 19(3):385-93.
32. Dagan R, Arguedas A, Schaad UB. Potential role of fluoroquinolone therapy in childhood otitis media. Pediatr Infect Dis J. 2004;23(5): 390-8.
33. Leyland-Jones B, Davies BR, Clagett-Carr K, Shoemaker D, Macfarlane D, Fortner C, et al. Patient treatment on a compassionate basis: documentation of high adverse drug reaction rate. Ann Oncol. 1992;3(1):59-62.
34. Brasil, Ministério da Saúde, Conselho Nacional da Saúde. Resolução CNS 01/88. Normas de pesquisa em saúde. Diário Oficial da União 1988. Brasília: Ministério da Saúde. 1988.
35. Brasil, Ministério da Saúde, Conselho Nacional da Saúde. Resolução CNS 196/96. Diretrizes e normas regulamentadoras de pesquisas envolvendo seres humanos. Diário Oficial da União; 1996. Brasília: Ministério da Saúde; 1996. Pp. 21082-5.
36. University of Western Ontario. Guideline UWO 2-G-010. Requests for REB approval of compassionate or emergency release of study drugs or treatment. London, Ontario: The Office of Research Ethics; 2006. Disponível em: http://www.uwo.ca/research/ethics/med/ 2G010%20GUIDELINE%20Compassionate %20&%20Emergency%20Release%20Sep%20 2006.pdf. Acessado em janeiro de 2008.
37. Estados Unidos, Food and Drug Administration. Emergency use of an investigational new drug (IND). Fed Reg. 2006;69(66):17927. Disponível em: http://69.20.19.211/cber/rules/emerguseind.htm. Acessado em janeiro de 2008.
38. Kimberlin DW, Lin CY, Jacobs RF, Powell DA, Corey L, Gruber WC, et al. Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections. Pediatrics. 2001;108(2):230-8.
39. Levine RJ. AIDS treatment drugs: clinical trials and compassionate use. AIDS Public Policy J. 1987;2(2):6-8.
40. Vogel CL, East DR, Voigt W, Thomsen S. Response to tamoxifen in estrogen receptor-poor metastatic breast cancer. Cancer. 1987;60(6): 1184-9.
41. Hsu C, Chen CN, Chen LT, Wu CY, Yang PM, Lai MY, et al. Low-dose thalidomide treatment for advanced hepatocellular carcinoma. Oncology. 2003;65(3):242-9.
42. Flach AJ. Delta-9-tetrahydrocannabinol (THC) in the treatment of end-stage open-angle glaucoma. Trans Am Ophthalmol Soc. 2002;100:215-22; discussion 222-4.
43. Szalavitz M. RU-486. Anti-choice extremists block HIV drug research. Notes Undergr. 1999(39):1,3-4,7.
44. Visani G, Tosi P, Gamberi B, Cenacchi A, Mazzanti P, Stabilini C, et al. Accelerated hemopoietic recovery after chemotherapy and autologous bone marrow transplantation in hematological malignancies using recombinant GM-CSF: preliminary results obtained in 14 cases. Haematologica. 1990;75(6):551-4.
45. Clive S, Gardiner J, Leonard RC. Miltefosine as a topical treatment for cutaneous metastases in breast carcinoma. Cancer Chemother Pharmacol. 1999;44 Suppl:S29-30.
46. Merck announces compassionate-treatment lottery for Crixivan. J Int Assoc Physicians AIDS Care. 1995;1(6):38.
47. Protease inhibitor: Roche lottery deadline July 21. AIDS Treat News. 1995;(226):4-5.
48. Ryan DP, Penson RT, Ahmed S, Chabner BA, Lynch TJ Jr. Reality testing in cancer treatment: the phase I trial of endostatin. Oncologist. 1999;4(6):501-8.
49. Steger GG, Bartsch R, Wenzel C, Pluschnig U, Hussian D, Sevelda U, et al. Fulvestrant ('Faslodex') in pre-treated patients with advanced breast cancer: a single-centre experience. Eur J Cancer. 2005;41(17):2655-61.
50. Pui CH. Urate oxidase in the prophylaxis or treatment of hyperuricemia: the United States experience. Semin Hematol. 2001;38(4 Suppl 10):13-21.
51. Liu CJ, Lai MY, Lee PH, Chou NK, Chu SH, Chen PJ, et al. Lamivudine treatment for hepatitis B reactivation in HBsAg carriers after organ transplantation: a 4-year experience. J Gastroenterol Hepatol. 2001;16(9):1001-8.
52. Bensmaine MA, Marty M, de Gramont A, Brienza S, Levi F, Ducreux M, et al. Factors predicting efficacy of oxaliplatin in combination with 5-fluorouracil (5-FU) +/- folinic acid in a compassionate-use cohort of 481 5-FU-resistant advanced colorectal cancer patients. Br J Cancer. 2001;85(4):509-17.
53. Chopra R, Eaton JD, Grassi A, Potter M, Shaw B, Salat C, et al. Defibrotide for the treatment of hepatic veno-occlusive disease: results of the European compassionate-use study. Br J Haematol. 2000;111(4):1122-9.
54. Carver PL, Whang E, VandenBussche HL, Kauffman CA, Malani PN. Risk factors for arthralgias or myalgias associated with quinupristin-dalfopristin therapy. Pharmacotherapy. 2003;23(2):159-64.
55. Hann HW, Fontana RJ, Wright T, Everson G, Baker A, Schiff ER, et al. A United States compassionate use study of lamivudine treatment in nontransplantation candidates with decompensated hepatitis B virus-related cirrhosis. Liver Transpl. 2003;9(1):49-56.
56. Wit FW; Dutch HIV-treating physicians. Experience with nevirapine in previously treated HIV-1-infected individuals. Antivir Ther. 2000;5(4):257-66.
57. Greenberg RN, Mullane K, van Burik JA, Raad I, Abzug MJ, Anstead G, et al. Posaconazole as salvage therapy for zygomycosis. Antimicrob Agents Chemother. 2006;50(1): 126-33.
58. Stengel D, Gorzer E, Schintler M, Legat FJ, Amann W, Pieber T, et al. Second-line treatment of limb-threatening diabetic foot infections with intravenous fosfomycin. J Chemother. 2005;17(5):527-35.
59. Aurer I, Radman I, Nemet D, Zupancic-Salek S, Bogdanic V, Mrsic M, et al. Gemcitabine in the treatment of relapsed and refractory Hodgkin's disease. Onkologie. 2005;28(11): 567-71.
60. Shin HY, Kang HJ, Park ES, Choi HS, Ahn HS, Kim SY, et al. Recombinant urate oxidase (Rasburicase) for the treatment of hyperuricemia in pediatric patients with hematologic malignancies: Results of a compassionate prospective multicenter study in Korea. Pediatr Blood Cancer. 2006;46(4):439-45.
61. LaRocca RV, Glisson SD, Hargis JB, Kosfeld RE, Leaton KE, Hicks RM, et al. Compassionate-use oxaliplatin with bolus 5-fluorouracil/leucovorin in heavily pretreated patients with advanced colorectal cancer. South Med J. 2004;97(9):831-5.
62. Mu XL, Li LY, Zhang XT, Wang SL, Wang MZ. Evaluation of safety and efficacy of gefitinib ('iressa', zd1839) as monotherapy in a series of Chinese patients with advanced non-small-cell lung cancer: experience from a compassionate-use programme. BMC Cancer. 2004;4:51.
63. Kartsonis NA, Saah A, Lipka CJ, Taylor A, Sable CA. Second-line therapy with caspofungin for mucosal or invasive candidiasis:
64. results from the caspofungin compassionate-use study. J Antimicrob Chemother. 2004; 53(5):878-81.
65. Rayner CR, Baddour LM, Birmingham MC, Norden C, Meagher AK, Schentag JJ. Linezolid in the treatment of osteomyelitis: results of compassionate use experience. Infection. 2004;32(1):8-14.
66. Chang SM, Theodosopoulos P, Lamborn K, Malec M, Rabbitt J, Page M, et al. Temozolomide in the treatment of recurrent malignant glioma. Cancer. 2004;100(3):605-11.
67. El-Khoury J, Fishman JA. Linezolid in the treatment of vancomycin-resistant Enterococcus faecium in solid organ transplant recipients: report of a multicenter compassionate-use trial. Transpl Infect Dis. 2003;5(3):121-5.
68. Ramanathan RK, Clark JW, Kemeny NE, Lenz HJ, Gococo KO, Haller DG, et al. Safety and toxicity analysis of oxaliplatin combined with fluorouracil or as a single agent in patients with previously treated advanced colorectal cancer. J Clin Oncol. 2003;21(15):2904-11.
69. Menten J, Desmedt M, Lossignol D, Mullie A. Longitudinal follow-up of TTS-fentanyl use in patients with cancer-related pain: results of a compassionate-use study with special focus on elderly patients. Curr Med Res Opin. 2002; 18(8):488-98.
70. Birmingham MC, Rayner CR, Meagher AK, Flavin SM, Batts DH, Schentag JJ. Linezolid for the treatment of multidrug-resistant, gram-positive infections: experience from a compassionate-use program. Clin Infect Dis. 2003;36(2):159-68.
71. Bellmunt J, Cos J, Cleries R, Perez M, Ribas A, Eres N, et al. Feasibility trial of methotrexatepaclitaxel as a second line therapy in advanced urothelial cancer. Cancer Invest. 2002; 20(5-6):673-85.68. Pui CH, Jeha S, Irwin D, Camitta B. Recombinant urate oxidase (rasburicase) in the
72. prevention and treatment of malignancy-associated hyperuricemia in pediatric and adult patients: results of a compassionate-use trial. Leukemia. 2001;15(10):1505-9.
73. Meunier F, Prentice HG, Ringden O. Liposomal amphotericin B (AmBisome): safety data from a phase II/III clinical trial. J Antimicrob Chemother. 1991;28 Suppl B:83-91.
74. Ball SE, Tchernia G, Wranne L, Bastion Y, Bekassy NA, Bordigoni P, et al. Is there a role for interleukin-3 in Diamond-Blackfan anaemia? Results of a European multicentre study. Br J Haematol. 1995;91(2):313-8.
75. Boischevalier B. Objectives of the Inserm Ethics Committee (ERMES) [site da Internet]. Disponível em: http://www.inserm.fr/en/ inserm/organisation/comites/ermes/. Acessado em 13 de dezembro 2006.
76. Organização das Nações Unidas para a Educação, a Ciência e a Cultura. Bioethics committees at work: procedures and policies. Paris: UNESCO; 2005.
77. Estados Unidos, Food and Drug Administration. Code of Federal Regulations Sec. 312.85 Phase 4 studies. Disponível em: http://www. accessdata.fda.gov/scripts/cdrh/cfdocs/cfC FR/CFRSearch.cfm?fr=312.85. Acessado em janeiro de 2008.