Pediatric Research in Maryland: Implications of the Krieger Case Jack Schwartz Director of Health Policy Maryland AG’s Office jschwartz@oag.state.md.us

The Krieger Study: Objective Efficacy of affordable lead abatement 3 groups of houses: varying levels of abatement 2 groups of control houses supposedly fully abated no lead paint ever used

The Krieger Study: Methods Testing for lead blood levels Testing for environmental lead levels dust soil water Questionnaires

Plaintiff #1: Ericka Grimes Infant, entered study via mother’s consent House was in control group (fully abated) Dust sample testing  lead “hot spots” No disclosure for 9 months Found to have EBL

Plaintiff #2: Myron Higgins 4 y/o, entered study via mother’s consent House was in an intervention group Found to have EBL

The plaintiffs’ case Negligence claims improper abatement methods failure to warn Ericka and Myron win only if Krieger: had a legally recognized duty to them breached that duty by the breach, caused them injury

Krieger’s short-lived win Krieger’s argument: no duty owed “Even if what the plaintiffs say were true, they still lose.” Trial court agrees grants Krieger’s motion for summary judgment No trial No factual record except plaintiffs’ allegations

Issue on appeal: existence of duty Court of Appeals reverses trial court Krieger did have a duty of care Sources: consent document = contract nature of “nontherapeutic” research federal regulations Nuremberg Code

Holding on parental authority Standard = best interest of the child Court’s view of the Krieger research Healthy children; no personal benefit Risk of permanent, serious harm Participation could not be in child’s best interest Therefore, no parental authority to consent

Bioethics commentary Krieger research deemed unethical disregard of potential harm to subjects inadequate informed consent Hopkins IRB deemed unethical regarded as an endemic problem Researchers had conflicts of interest financial and scientific incentives

Lessons of the case for pediatric researchers Consider issue of parental authority suggested algorithm Describe risks and benefits fairly and fully in protocol Conduct genuine informed consent process Ensure provision of information to parents as promised if material to decision whether child should continue in research

Step 1: Any therapeutic procedures involved? Therapeutic = evidence-based possibility of direct medical benefit Nontherapeutic = done solely to answer the scientific question Weijer C & Miller PB. When are research risks reasonable in relation to anticipated benefits? Nature Med 2004; 10: 570-73. If NO  Parental authority probably limited to minimal risk If YES  To Step 2

Step 2: Clinical equipoise? Are therapeutic procedures consistent with competent medical care? If NO  No parental authority Not in child’s best interest to forgo preferable care If YES  To Step 3

Step 3: Potential direct benefits worth the risk? Are risks of therapeutic procedures justified by prospect of direct benefit? If NO  No parental authority If YES  To Step 4

Step 4: Risk of nontherapeutic procedures minimized? Are risks of nontherapeutic procedures minimized consistent with sound scientific design? If NO  No parental authority If YES  To Step 5

Step 5: Risk of nontherapeutic procedures justified? Are risks of nontherapeutic procedures no more than a minor increase over minimal and justified by scientific value? If NO  No parental authority If YES  Parental permission allowed

Applying the analysis: Phase 1 oncology trials Is test article a therapeutic procedure? By FDA definition, not an efficacy trial But: what if no clinical alternative for hope of remission? Depending on facts about child, research, and alternatives: Answer might be “Yes” to all Parental best interest judgment possible

Applying the analysis: prophylactic vaccine trials Is test article a therapeutic procedure? Therapeutic for healthy subjects? Maybe, depending on risk of future disease If IRB finds it not a therapeutic procedure: > minimal risk No parental authority If IRB finds it a therapeutic procedure: Answer might be “Yes” to all Parental best interest judgment possible

Applying the analysis: epidemiology Probably no therapeutic procedures What are risks of the nontherapeutic procedures? Typical questionnaire = minimal risk Typical phlebotomy = minimal risk Identification of heightened genetic risk = more than minimal risk?