Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Review article: Medical guidelines

Vol. 150 No. 3940 (2020)

Including adolescents of childbearing potential in clinical trials with possible exposure to teratogenic medication: a challenge for paediatricians and researchers

DOI
https://doi.org/10.4414/smw.2020.20333
Cite this as:
Swiss Med Wkly. 2020;150:w20333
Published
25.09.2020

Summary

The issue of contraception and pregnancy tests among minor adolescent women participating in clinical trials, whether healthy or suffering from a disease, represents a challenging issue for paediatricians and researchers, given the potential harmful effect of various therapeutic procedures being tested. First, they need to gauge at what age or developmental stage they need to impose pregnancy tests and contraception. Second, if the adolescent denies any sexual activity, it may be ethically questionable to impose such procedures. Third, these professionals must deal with the issue of confidentiality, taking into account the fact that some adolescents engage in penetrative sexual intercourse without their parents or caregivers knowing. Fourth, in such cases, they must assess the extent to which a minor adolescent can be considered as competent (capable of making autonomous decisions) and deserves privacy and confidentiality. There is indeed a legal obligation for the provider to check that sexual experiences and intercourse take place within a safe relationship. Fifth, if the prescription of contraception is warranted, they have to decide who should assist the adolescent in choosing the method. Finally, with the occurrence of a positive pregnancy test, they may face the rare instance of a competent minor adolescent who refuses to inform her parents. This article has been developed by a group of experts under the auspices of swissethics, the Swiss Association of Research Ethics Committees and SwissPedNet, the umbrella organisation that coordinates the paediatric research in Switzerland. The paper reviews how to address practical and ethical questions regarding minor adolescents of childbearing potential enrolled in a clinical trial that may involve teratogenic medication and offers a series of concrete advice and tools for dealing with problematic situations.

Most paediatric protocols stipulate that adolescents included in clinical trials involving potentially teratogenic drugs should undergo pregnancy tests and use contraception. The circumstances in which such requirements are undertaken, however, has not been sufficiently addressed.

The recommendations presented in this article will assist researchers in assessing which circumstances apply when considering minor adolescents as individuals with childbearing potentials. It also offers concrete suggestions for tackling such situations.

References

  1. European Medicines Agency. ICH guideline M3(R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals. London: European Medicines Agency; 2009. 26 pp.
  2. Michaud PA, Berg-Kelly K, Macfarlane A, Benaroyo L. Ethics and adolescent care: an international perspective. Curr Opin Pediatr. 2010;22(4):418–22. doi:.https://doi.org/10.1097/MOP.0b013e32833b53ec
  3. Michaud PA, Blum RW, Benaroyo L, Zermatten J, Baltag V. Assessing an Adolescent’s Capacity for Autonomous Decision-Making in Clinical Care. J Adolesc Health. 2015;57(4):361–6. doi:.https://doi.org/10.1016/j.jadohealth.2015.06.012
  4. Zhang K, Pollack S, Ghods A, Dicken C, Isaac B, Adel G, et al. Onset of ovulation after menarche in girls: a longitudinal study. J Clin Endocrinol Metab. 2008;93(4):1186–94. doi:.https://doi.org/10.1210/jc.2007-1846
  5. Kleist P, Driessen S, Gervasoni P. Leitlinie zur Forschung mit gesunden Kindern und Jugenlichen. Bern: Swissethics; 2017.49 pp.
  6. Modi N, Vohra J, Preston J, Elliott C, Van’t Hoff W, Coad J, et al.; Working Party of the Royal College of Paediatrics and Child Health. Guidance on clinical research involving infants, children and young people: an update for researchers and research ethics committees. Arch Dis Child. 2014;99(10):887–91. doi:.https://doi.org/10.1136/archdischild-2014-306444
  7. World Health Organization. Guidance on ethical considerations in planning and reviewing research studies on sexual and reproductive health in adolescents. Geneva: World Health Organization; 2018. 52 pp.
  8. World Health Organization. WHO recommendations on adolescent sexual and reproductive health and rights. Geneva: World Health Organization; 2018. 77 pp.
  9. Graham A, Powell M, Taylor N, et al. Ethical Research Involving Children. Florence: UNICEF Office of Research – Innocenti; 2013. 220 pp.
  10. Singh JA, Siddiqi M, Parameshwar P, Chandra-Mouli V. World Health Organization Guidance on Ethical Considerations in Planning and Reviewing Research Studies on Sexual and Reproductive Health in Adolescents. J Adolesc Health. 2019;64(4):427–9. doi:.https://doi.org/10.1016/j.jadohealth.2019.01.008
  11. Santelli J, Haerizadeh S, McGovernz T. Inclusion with Protection: Obtaining informed consent when conducting research with adolescents. New-York: Mailman School of Public Health, Columbia University; 2017.18 pp.
  12. Tanner J. Growth at Adolescence. 2nd. ed. Oxford: Blackwell Scientific Publications; 1962.
  13. Gossain VV, Carella MJ, Rovner DR. Pregnancy in a patient with premature ovarian failure. J Med. 1993;24(6):393–402. [published Online First: 1993/01/01].
  14. Coleman L, Coleman J. The measurement of puberty: a review. J Adolesc. 2002;25(5):535–50. doi:.https://doi.org/10.1006/jado.2002.0494
  15. Berg-Kelly K, Erdes L. Self-assessment of sexual maturity by mid-adolescents based on a global question. Acta Paediatr. 1997;86(1):10–7. doi:.https://doi.org/10.1111/j.1651-2227.1997.tb08822.x
  16. Barrense-Dias Y, Akre C, Berchtold A, et al. Sexual health and behavior of young people in Switzerland. In: Institut universitaire de médecine sociale et préventive, ed. Raisons de santé. Lausanne: IUMSP Institut universitaire de médecine sociale et préventive, 2018:116 pp.
  17. Steinberg L. Age of Opportunity: Lessons from the New Science of Adolescence. New York: Houghton MifflinHarcourt Publishing Company; 2014.
  18. Steinberg L, Morris AS. Adolescent development. Annu Rev Psychol. 2001;52(1):83–110. doi:.https://doi.org/10.1146/annurev.psych.52.1.83
  19. Michaud PA, Suris JC, Viner R. The adolescent with a chronic condition. Part II: healthcare provision. Arch Dis Child. 2004;89(10):943–9. doi:.https://doi.org/10.1136/adc.2003.045377
  20. Surís JC, Michaud PA, Akre C, Sawyer SM. Health risk behaviors in adolescents with chronic conditions. Pediatrics. 2008;122(5):e1113–8. doi:.https://doi.org/10.1542/peds.2008-1479
  21. Pampati S, Liddon N, Dittus PJ, Adkins SH, Steiner RJ. Confidentiality Matters but How Do We Improve Implementation in Adolescent Sexual and Reproductive Health Care? J Adolesc Health. 2019;65(3):315–22. doi:.https://doi.org/10.1016/j.jadohealth.2019.03.021
  22. Larcher V. Consent, competence, and confidentiality. BMJ. 2005;330(7487):353–6. doi:.https://doi.org/10.1136/bmj.330.7487.353
  23. World Health Organization. Children’s rights in primary health care. Assessment and improvement Tool for Children and Adolescents aged 12-18. Copenhagen: World Health Organization; 2015. 50 pp.
  24. United Nation General Assembly. United Nation Convention on the Rights of the Child. New York: United Nation General Assembly; 1990.
  25. Caldwell JC, Caldwell P, Caldwell BK, Pieris I. The construction of adolescence in a changing world: implications for sexuality, reproduction, and marriage. Stud Fam Plann. 1998;29(2):137–53. doi:.https://doi.org/10.2307/172155
  26. Kao TS, Guthrie B, Loveland-Cherry C, Caldwell CH. Cross-cultural variations in adolescents’ perceived maternal expectancy and sexual initiation. J Transcult Nurs. 2012;23(4):377–88. doi:.https://doi.org/10.1177/1043659612452669
  27. Steinberg L. Cognitive and affective development in adolescence. Trends Cogn Sci. 2005;9(2):69–74. doi:.https://doi.org/10.1016/j.tics.2004.12.005
  28. Zdunek K, Alma M, Van Til J, et al. Listening to Young People. In: Blair M, Rigny, M, Alexander, D, ed. Issues and opportunities in primary health care for children in Europe. Bingley, UK: Emerald Publishing Limited; 2019. pp 55–76.
  29. Council of Europe. Council of Europe guidelines on child-friendly health care. Strasbourg: Council of Europe; 2011. 20 pp.
  30. Griffith R, Tengnah C. Assessing children’s competence to consent to treatment. Br J Community Nurs. 2012;17(2):87–90. doi:.https://doi.org/10.12968/bjcn.2012.17.2.87
  31. Hein IM, Troost PW, Lindeboom R, Benninga MA, Zwaan CM, van Goudoever JB, et al. Key factors in children’s competence to consent to clinical research. BMC Med Ethics. 2015;16(1):74. doi:.https://doi.org/10.1186/s12910-015-0066-0
  32. Lamont S, Jeon YH, Chiarella M. Assessing patient capacity to consent to treatment: an integrative review of instruments and tools. J Clin Nurs. 2013;22(17-18):2387–403. doi:.https://doi.org/10.1111/jocn.12215
  33. Larcher V, Hutchinson A. How should paediatricians assess Gillick competence? Arch Dis Child. 2010;95(4):307–11. doi:.https://doi.org/10.1136/adc.2008.148676
  34. Hein IM, De Vries MC, Troost PW, Meynen G, Van Goudoever JB, Lindauer RJ. Informed consent instead of assent is appropriate in children from the age of twelve: Policy implications of new findings on children’s competence to consent to clinical research. BMC Med Ethics. 2015;16(1):76. doi:.https://doi.org/10.1186/s12910-015-0067-z
  35. Stevens-Simon C. Assent in pediatric research. Pediatrics. 2006;118(4):1800–1, author reply 1801. doi:.https://doi.org/10.1542/peds.2006-1577
  36. Hein IM, Troost PW, Lindeboom R, et al. Assesing children's competence to consent to treatment. In: AHein I, ed. Children's competence to consent to medical treatment or research. Amsterdam: Amsterdam University Press; 2015. pp 91–101.
  37. Goldenring JM, Rosen D. Getting into adolescent heads: an essential update. Contemp Pediatr. 2004;21(4):64–80.
  38. Larcher V. Developing guidance for checking pregnancy status in adolescent girls before surgical, radiological or other procedures. Arch Dis Child. 2012;97(10):857–60. doi:.https://doi.org/10.1136/archdischild-2012-302016
  39. Zdunek K, Rigby M, Deshpande S, et al. Child Centricity and Children's Rights. In: Blair M, Rigny, M, Alexander, D, ed. Issues and opportunities in primary health care for children in Europe. Bingley, UK: Emerald Publishing Limited; 2019. p 77–98.
  40. Burke TM, Abramovitch R, Zlotkin S. Children’s understanding of the risks and benefits associated with research. J Med Ethics. 2005;31(12):715–20. doi:.https://doi.org/10.1136/jme.2003.003228
  41. Gibson BE, Stasiulis E, Gutfreund S, McDonald M, Dade L. Assessment of children’s capacity to consent for research: a descriptive qualitative study of researchers’ practices. J Med Ethics. 2011;37(8):504–9. doi:.https://doi.org/10.1136/jme.2010.040097
  42. Mack JW, Joffe S. Communicating about prognosis: ethical responsibilities of pediatricians and parents. Pediatrics. 2014;133(Suppl 1):S24–30. doi:.https://doi.org/10.1542/peds.2013-3608E
  43. Massimo LM, Wiley TJ, Casari EF. From informed consent to shared consent: a developing process in paediatric oncology. Lancet Oncol. 2004;5(6):384–7. doi:.https://doi.org/10.1016/S1470-2045(04)01496-2
  44. Steinberg L. Does recent research on adolescent brain development inform the mature minor doctrine? J Med Philos. 2013;38(3):256–67. doi:.https://doi.org/10.1093/jmp/jht017
  45. Jaccard J, Levitz N. Counseling adolescents about contraception: towards the development of an evidence-based protocol for contraceptive counselors. J Adolesc Health. 2013;52(4, Suppl):S6–13. doi:.https://doi.org/10.1016/j.jadohealth.2013.01.018
  46. Diserens C, Quach A, Mathevet P, Ballabeni P, Jacot-Guillarmod M. Adolescents’ contraception continuation in Switzerland: a prospective observational study. Swiss Med Wkly. 2017;147:w14504. doi:.https://doi.org/10.4414/smw.2017.14504
  47. Jacot-Guillarmod M, Diserens C. Contraception chez les adolescentes. Swiss Medical Forum. 2019;19(21–22):354–60. doi:.https://doi.org/10.4414/smf.2019.08067
  48. Pienkowski C, Cartault A. Contraception de l’adolescente. RPC Contraception CNGOF [Contraception for adolescent : CNGOF Contraception guidelines]. Gynécol Obstét Fertil Sénol. 2018;46(12):858–64. doi:.https://doi.org/10.1016/j.gofs.2018.10.034
  49. Coles CB, Shubkin CD. Effective, recommended, underutilized: a review of the literature on barriers to adolescent usage of long-acting reversible contraceptive methods. Curr Opin Pediatr. 2018;30(5):683–8. doi:.https://doi.org/10.1097/MOP.0000000000000663
  50. Clinical Trial Facilitating Group CTFG. Recommendations related to contraception and pregnancy testing in clinical trials. In: Agency EM, ed. Langen, Germany: Clinical Trial Facilitating Group CTFG; 2014. 13 pp.
  51. Cook RJ, Erdman JN, Dickens BM. Respecting adolescents’ confidentiality and reproductive and sexual choices. Int J Gynaecol Obstet. 2007;98(2):182–7. doi:.https://doi.org/10.1016/j.ijgo.2007.04.018
  52. Narring F. Adolescent Pregnancy in Switzerland. In: Springer, ed. International Handbook of Adolescent Pregnancy. Heidelberg: Springer; 2014. pp 599–604.
  53. Cherry A, Dillon ME. International Handbook on Adolescent Pregnancy. New York: Springer; 2014.
  54. Michaud PA, Jansen D, Schrier L, Vervoort J, Visser A, Dembiński Ł. An exploratory survey on the state of training in adolescent medicine and health in 36 European countries. Eur J Pediatr. 2019;178(10):1559–65. doi:.https://doi.org/10.1007/s00431-019-03445-1

Most read articles by the same author(s)