Ethical Considerations of Biologics to Treat Substance Use Disorders

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Abstract

The development of biologic products to treat substance use disorders (SUDs) poses important and sometimes unique ethical challenges due to the clinical characteristics of patients with the disorders and the nature of these products. Historically, there has been a great deal of discussion about the ethics of conducting clinical research in individuals with SUDs. They include the stigma associated with drug abuse, the legal issues associated with disclosing the use of illicit drugs, and the protection of subject’s confidentiality from disclosure of potentially harmful information. Moreover, the behavioral manifestations associated with SUDs, which often include chaotic lifestyles, may hinder recruitment and retention of subjects in clinical studies, study protocol adherence, and reliability of self-reported data (Cohen 1997). Recently, biologics such as vaccines, monoclonal antibodies, and enzymes have been investigated to treat SUDs because they prevent the access of drugs of abuse to the brain, attenuate their rewarding effects, and protect against drug use relapse. Currently, there are no biologics approved by the Food and Drug Administration (FDA) for any SUDs. New products, as well as new and more efficient methods of production, are offering vast opportunities to advance the discovery and development of biologics to treat SUDs and drug overdose. The purpose of this chapter is to provide an overview of some ethical issues of clinical studies of SUDs, each of type of the biologic product, and the clinical indications being investigated.

Keywords

Nicotine Dependence Drug Overdose Cocaine Dependence Abuse Liability Ecgonine Methyl Ester 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. Adler MW. Human subject issues in drug abuse research. College on problems of drug dependence. Drug Alcohol Depend. 1995;37:167–75.PubMedGoogle Scholar
  2. Almond B. Drug use and abuse: the ethical issues. Ciba Found Symp. 1992;166:277–83.PubMedGoogle Scholar
  3. Ashcroft RE, Franey C. Further ethical and social issues in using a cocaine vaccine: response to Hall and Carter. J Med Ethics. 2004;30:341–3.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Bailey TC, Sugarman J. Social justice and HIV vaccine research in the age of pre-exposure prophylaxis and treatment as prevention. Curr HIV Res. 2013;11:473–80.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bonese KF, Wainer BH, Fitch FW, Rothberg RM, Schuster CR. Changes in heroin self-administration by a rhesus monkey after morphine immunisation. Nature. 1974;252:708–10.CrossRefPubMedGoogle Scholar
  6. Carroll KM, Kiluk BD, Nich C, DeVito EE, Decker S, LaPaglia D, et al. Toward empirical identification of a clinically meaningful indicator of treatment outcome: features of candidate indicators and evaluation of sensitivity to treatment effects and relationship to one year follow up cocaine use outcomes. Drug Alcohol Depend. 2014;137:3–19.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Carter A, Hall W. Ethical implications of research on craving. Addict Behav. 2013;38:1593–9.CrossRefPubMedGoogle Scholar
  8. Chapman K, Pullen N, Coney L, Dempster M, Andrews L, Bajramovic J, et al. Preclinical development of monoclonal antibodies: considerations for the use of non-human primates. MAbs. 2009;1:505–16.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Chapman KL, Andrews L, Bajramovic JJ, Baldrick P, Black LE, Bowman CJ, et al. The design of chronic toxicology studies of monoclonal antibodies: implications for the reduction in use of non-human primates. Regul Toxicol Pharmacol. 2012;62:347–54.CrossRefPubMedGoogle Scholar
  10. Chapman KL, Pullen N, Andrews L, Ragan I. The future of non-human primate use in mAb development. Drug Discov Today. 2010;15:235–42.CrossRefPubMedGoogle Scholar
  11. Cohen PJ. Immunization for prevention and treatment of cocaine abuse: legal and ethical implications. Drug Alcohol Depend. 1997;48:167–74.CrossRefPubMedGoogle Scholar
  12. Fang L, Chow KM, Hou S, Xue L, Chen X, Rodgers DW, et al. Rational design, preparation, and characterization of a therapeutic enzyme mutant with improved stability and function for cocaine detoxification. ACS Chem Biol. 2014;9:1764–72.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Garner SA, Anude CJ, Adams E, Dawson L. Ethical considerations in HIV prevention and vaccine research in resource-limited settings. J Acquir Immune Defic Syndr. 2014;67:77–83.CrossRefPubMedGoogle Scholar
  15. Glassy MC, Gupta R. Technical and ethical limitations in making human monoclonal antibodies (an overview). Methods Mol Biol. 2014;1060:9–36.CrossRefPubMedGoogle Scholar
  16. Gorelick DA. Pharmacokinetic approaches to treatment of drug addiction. Expert Rev Clin Pharmacol. 2008;1:277–90.CrossRefPubMedGoogle Scholar
  17. Grady C. Ethics of vaccine research. Nat Immunol. 2004;5:465–8.CrossRefPubMedGoogle Scholar
  18. Hall W, Carter L, Morley KI. Neuroscience research on the addictions: a prospectus for future ethical and policy analysis. Addict Behav. 2004;29:1481–95.CrossRefPubMedGoogle Scholar
  19. Hall W, Gartner C. Ethical and policy issues in using vaccines to treat and prevent cocaine and nicotine dependence. Curr Opin Psychiatry. 2011;24:191–6.CrossRefPubMedGoogle Scholar
  20. Hasman A, Holm S. Nicotine conjugate vaccine: is there a right to a smoking future? J Med Ethics. 2004;30:344–5.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Henderson GE. The ethics of HIV “cure” research: what can we learn from consent forms? AIDS Res Hum Retroviruses. 2015;31:56–63.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Kantak KM. Vaccines against drugs of abuse: a viable treatment option? Drugs. 2003;63:341–52.CrossRefPubMedGoogle Scholar
  23. Katsnelson A. Ethical quagmire awaits vaccine for cocaine addiction. Nat Med. 2004;10:1007.CrossRefPubMedGoogle Scholar
  24. Kiluk BD, Nich C, Witkiewitz K, Babuscio TA, Carroll KM. What happens in treatment doesn’t stay in treatment: cocaine abstinence during treatment is associated with fewer problems at follow-up. J Consult Clin Psychol. 2014;82:619–27.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Kingham R, Klasa G, Hessler Carver K. Key regulatory guidelines for the development of biologics in the United States and Europe. In: Wang W, Singh M, editors. Biological drug products: development and strategies. 1st ed. Hoboken, New Jersey: John Wiley & Sons, Inc.; 2014.Google Scholar
  26. Kingham RF, Lietzan E. Current regulatory and legal considerations for follow-on biologics. Clin Pharmacol Ther. 2008;84:633–5.CrossRefPubMedGoogle Scholar
  27. Kleber HD. Drug abuse liability testing: human subject issues. NIDA Res Monogr. 1989;92:341–56.PubMedGoogle Scholar
  28. Lee JD, Friedmann PD, Boney TY, Hoskinson Jr RA, McDonald R, Gordon M, et al. Extended-release naltrexone to prevent relapse among opioid dependent, criminal justice system involved adults: rationale and design of a randomized controlled effectiveness trial. Contemp Clin Trials. 2015;41:110–7.CrossRefPubMedPubMedCentralGoogle Scholar
  29. Liedert B, Bassus S, Schneider CK, Kalinke U, Lower J. Safety of phase I clinical trials with monoclonal antibodies in Germany—the regulatory requirements viewed in the aftermath of the TGN1412 disaster. Int J Clin Pharmacol Ther. 2007;45:1–9.CrossRefPubMedGoogle Scholar
  30. Lo B, Grady C. Ethical considerations in HIV cure research: points to consider. Curr Opin HIV AIDS. 2013;8:243–9.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Lynch CM, Hart BW, Grewal IS. Practical considerations for nonclinical safety evaluation of therapeutic monoclonal antibodies. MAbs. 2009;1:2–11.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Mendelson JH. Protection of participants and experimental design in clinical abuse liability testing. Br J Addict. 1991;86:1543–8.CrossRefPubMedGoogle Scholar
  33. Meyer MR, Schutz A, Maurer HH. Contribution of human esterases to the metabolism of selected drugs of abuse. Toxicol Lett. 2014;232:159–66.CrossRefPubMedGoogle Scholar
  34. Montoya I. Immunotherapies for drug addictions. Adicciones. 2008;20:111–5.CrossRefPubMedPubMedCentralGoogle Scholar
  35. Murthy V, Geng L, Gao Y, Zhang B, Miller JD, Reyes S, et al. Reward and toxicity of cocaine metabolites generated by cocaine hydrolase. Cell Mol Neurobiol. 2015;35(6):819–26.CrossRefPubMedPubMedCentralGoogle Scholar
  36. Narasimhan D, Woods JH, Sunahara RK. Bacterial cocaine esterase: a protein-based therapy for cocaine overdose and addiction. Future Med Chem. 2012;4:137–50.CrossRefPubMedPubMedCentralGoogle Scholar
  37. Nasser AF, Fudala PJ, Zheng B, Liu Y, Heidbreder C. A randomized, double-blind, placebo-controlled trial of RBP-8000 in cocaine abusers: pharmacokinetic profile of rbp-8000 and cocaine and effects of RBP-8000 on cocaine-induced physiological effects. J Addict Dis. 2014;33:289–302.CrossRefPubMedGoogle Scholar
  38. Owens SM, Atchley WT, Hambuchen MD, Peterson EC, Gentry WB. Monoclonal antibodies as pharmacokinetic antagonists for the treatment of (+)-methamphetamine addiction. CNS Neurol Disord Drug Targets. 2011;10:892–8.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Pitas G, Laurenzana EM, Williams DK, Owens SM, Gentry WB. Anti-phencyclidine monoclonal antibody binding capacity is not the only determinant of effectiveness, disproving the concept that antibody capacity is easily surmounted. Drug Metab Dispos. 2006;34:906–12.PubMedGoogle Scholar
  40. Pravetoni M, Le NM, Tucker AM, Harmon TM, Hawley TM, Portoghese PS, et al. Reduced antinociception of opioids in rats and mice by vaccination with immunogens containing oxycodone and hydrocodone haptens. J Med Chem. 2013;56:915–23.CrossRefPubMedPubMedCentralGoogle Scholar
  41. Pravetoni M, Raleigh MD, Le NM, Tucker AM, Harmon TM, Jones JM, et al. Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats. Vaccine. 2012;30:4617–24.CrossRefPubMedPubMedCentralGoogle Scholar
  42. Roberts SA, Andrews PA, Blanset D, Flagella KM, Gorovits B, Lynch CM, et al. Considerations for the nonclinical safety evaluation of antibody drug conjugates for oncology. Regul Toxicol Pharmacol. 2013;67:382–91.CrossRefPubMedGoogle Scholar
  43. Schneider CK. First-in-human trials with therapeutic proteins: regulatory rethink? Expert Rev Clin Pharmacol. 2008a;1:327–31.CrossRefPubMedGoogle Scholar
  44. Schneider CK. Monoclonal antibodies – regulatory challenges. Curr Pharm Biotechnol. 2008b;9:431–8.CrossRefPubMedGoogle Scholar
  45. Sugarman J, Rose SM, Metzger D. Ethical issues in HIV prevention research with people who inject drugs. Clin Trials. 2014;11:239–45.CrossRefPubMedGoogle Scholar
  46. Wolters A, de Wert G, van Schayck O, Horstman K. Vaccination against smoking: an annotated agenda for debate. A review of scientific journals, 2001-13. Addiction. 2014a;109:1268–73.CrossRefPubMedGoogle Scholar
  47. Wolters A, de Wert G, van Schayck O, Horstman K. Constructing a trial as a personal lifestyle change project: participants’ experiences in a clinical study for nicotine vaccination. Soc Sci Med. 2014b;104:116–23.CrossRefPubMedGoogle Scholar
  48. Young MJ, Sisti DA, Rimon-Greenspan H, Schwartz JL, Caplan AL. Immune to addiction: the ethical dimensions of vaccines against substance abuse. Nat Immunol. 2012;13:521–4.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Division of Therapeutics and Medical Consequences of Drug AbuseNational Institute on Drug AbuseBethesdaUSA

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