Ethical Dilemmas in Drug Development in ASD

Background:  Developing new drugs for the core features of autism spectrum disorder (ASD) will involve compounds that are not commercially available. Although ASD begins in early childhood, the regulatory pathway for drug approval usually starts with healthy (unaffected) adults, followed by adults with the disorder of interest, then advancing to pediatric trials.

Objectives:  The purpose of this presentation is to describe the ethical issues confronting drug development in ASD with particular focus on the inclusion of subjects with intellectual disability.

Methods:  We reviewed available literature to identify the web of ethical issues inherent in drug development programs for ASD.

Results:  First, we note that approximately half of the ASD population has an additional diagnosis of intellectual disability (ID). A history of past unethical research and clinical practices involving individuals with ID has prompted calls for additional protection of individuals with ID who participate in clinical research. This appropriate concern about exploitation of a vulnerable population, however, must be balanced with the problem of excluding these subjects from research with the potential of benefit.  Therapeutic benefit observed in studies including only higher-functioning participants with ASD may not generalize to individuals with ASD and ID.  Furthermore, individuals with ASD and ID are more likely to have serious behavioral problems, such as self-injurious behavior, that are often refractory to current drug treatments and may benefit from novel approaches. A second ethical dilemma arises from the fact that early clinical drug trials may focus on drug mechanism and may not provide direct benefit to individual subjects. Confirmation of the drug mechanism may be an important step in drug development and may result in societal benefit. However, subjects who benefit from treatment in an early drug trial may not have access to the drug after the trial due to uncertainty about long-term effects of new compounds.  Although benefit to society is an acceptable rationale for proceeding with studies that do not provide direct benefit to participants, the hard fact that the drug will not be available - even if it helps - may be a difficult concept to communicate to developmentally disabled participants. At the same time, societal benefit may be reduced if subjects with ID are not included in trials of drugs from which they may benefit.

Conclusions: Drug development in ASD should include subjects across the full range of intellectual functioning.  Critical discussions are needed to work through concerns of exploitation and exclusion of subjects in need of new treatments.