Maryland Law and Clinical Research:

Finding a Way Forward

Jack Schwartz

Director of Health Policy

Maryland AG’s Office

jschwartz@oag.state.md.us

Topics

The impact of the Krieger decision Parental authority to allow their kids in research

Evolution and scope of the Maryland statute Evaluation?

Research with incapacitated subjects Improved practice, new law?

Impact of the Krieger decision

Grimes v. Kennedy Krieger: the plaintiffs’ case

Negligence claims Improper abatement methods Failure to warn

Plaintiffs win only if Krieger: Had a legally recognized duty to them Breached that duty By the breach, caused them injury

Krieger’s Pyrrhic victory

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

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

Maryland’s research statute

Basic information

Bill reference: House Bill 917 of 2002 Passed House 135-1, passed Senate 47-0 Statutory reference: new §§ 13-1601 to 13-

1604, Health-General Article, Maryland Code Effective date: October 1, 2002

Extending federal regulations

All human subject research must comply with HHS or FDA regulations Note: requires compliance with all of 45 CFR Part

46, not just Common Rule Should have no effect on FWA institutions

Allows exemptions/waivers authorized under federal regulations

Issue: Does HB 917 apply to research begun prior to October 1, 2002?

Access to minutes

Roughly comparable to FOIA process Allow inspection within 30 days of request

“Confidential or privileged information” may be redacted

Issue: What is “confidential or privileged”? Issue: Is access granted to minutes created

before October 1, 2002?

Attorney General enforcement

Needed for research outside OHRP jurisdiction

Authority to seek court order for compliance No authority to regulate No appropriation for enforcement unit

respond to complaints only AG will coordinate with, defer to, OHRP

Has the bill made any difference?

AG’s Office would like to find out possibility of questionnaire to IRBs

Previously unreviewed research now sent to IRB?

Effect of provision on minutes? Impact on conduct of meeting? Content of minutes? Number of requests?

Epstein’s Law: If you think the problem is bad now, just wait until we’ve solved it.

Subjects with questionable or impaired capacity

Subjects with questionable capacity

Problem: capacity assessment If capable, no issue different from research generally If incapable, special protections

Response No regulatory provisions Therefore, left to self-regulation More attention in institutional practice/policy?

Central Maryland Alzheimer’s Association recommendations Alz Dis & Assoc Dis 2004; 18: 171-75

Subjects with obvious incapacity

Problem: identifying a proxy Response

Informed consent needed from “legally authorized representative” (45 CFR § 46.116)

No regulatory specification about who is a “legally authorized representative” Guardian? DPA for health care? Default health care

proxy?

OHRP queries Deference re interpretation of state law

The uncertainties of current law

Problem Tort liability if no legal authority

Consent would be invalid; battery or negligence Constructions of health care proxy laws untested

Response: specific state law CA and VA statutes, TN regulation Contentious or unaddressed issues

Risk limitations Decisionmaking criteria Role of research advance directives