Pediatric Research in Maryland Implications of the Krieger

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

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

Plaintiff #1: Ericka Grimes l l l 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 l l l 4 y/o, entered study via mother’s consent House was in an intervention group Found to have EBL

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

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

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

Holding on parental authority l l Standard = best interest of the child Court’s view of the Krieger research l l 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 l Krieger research deemed unethical l Hopkins IRB deemed unethical l l disregard of potential harm to subjects inadequate informed consent regarded as an endemic problem Researchers had conflicts of interest l financial and scientific incentives

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

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

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

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

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

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

Applying the analysis: Phase 1 oncology trials l Is test article a therapeutic procedure? l l l 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: l l Answer might be “Yes” to all Parental best interest judgment possible

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

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