# Presentation: 162932

## New Treatments for Addiction:Behavioral, Ethical, Legal, and Social Questions

- Committee on Immunotherapies and Sustained-Release Formulations for Treating Drug Addiction
- Henrick J. Harwood and Tracy G. Myers,  editors

## Committee Charge

- Advise NIDA about behavioral, ethical, legal, and social issues concerning potential uses of immunotherapies and sustained-release formulations.
- Asked for consensus about potential issues.
- Decide which issues are the most pressing.

## Committee on Immunotherapies and Sustained-Release Formulations for Treating Drug Addiction

**HENRICK J. HARWOOD (C*****hair)*****, The Lewin Group**
**ALEXANDER M. CAPRON, Pacific Center for Health Policy and Ethics, Univ. of Southern California**
**JONATHAN P. CAULKINS, Heinz School of Public Policy and Management, Carnegie Mellon Univ.**
**JAMES W. CORNISH, Philadelphia Department of Veterans Affairs Medical Center and Univ. of Pennsylvania Department of Psychiatry**
**LEWIS E. GALLANT, National Association of State Alcohol and Drug Abuse Directors, Inc., **
**SHIRLEY Y. HILL, Univ. of Pittsburgh School of Medicine**
**MARTIN Y. IGUCHI, Drug Policy Research Center, RAND Corporation**

**THOMAS R. KOSTEN, Yale Univ. Medical School**
**JOSEPH O. MERRILL, Harborview Medical Center and Univ. of Washington**
**S. MICHAEL OWENS, Univ. of Arkansas for Medical Sciences**
**CHARLES R. SCHUSTER, Department of Psychiatry and Behavioral Neurosciences, Wayne State Univ.**
**ZILI SLOBODA, Institute for Health and Social Policy, Univ. of Akron**
**KATHRYN E. STEIN, Macrogenics, Inc., **
**ELLEN M. WEBER, Univ. of Maryland School of Law**
**TRACY G. MYERS, Study Director**
**WENDY KEENAN, Senior Project Assistant**

## Commissioned Paper Authors and Topics

- Paul Pentel, Science Issues
- Thomas Kosten and Henry Kranzler, Clinical Trials
- George Woody, Lessons Learned
- Cindy Parks Thomas and Dennis McCarty, Integration with Current Treatment Systems
- M. Susan Ridgeley, Martin Iguchi, and James Chiesa, Legality of Mandated Treatment
- Thomas Murray, Ethics and Consent
- Mark Kleiman, Costs and Benefits
- Robert MacCoun, Behavioral Responses
- Frances Miller and Kaley Klanica, Treatment of Minors

## Major Themes and Issues

- Great need for medications and great promise
- Risk of over-promising, not a “magic bullet”
- Risk from unintended behavioral reactions
- Special problems consent/coercion
- Risks of off-label use
- Some health care systems not ready for these therapies
- Need for new standards of treatment success
***What NIDA can do . . . and the private sector is unlikely to do: 10 primary recommendations***

## Medical Basis of Medications	

- Active Immunization
- No immediate response (first response delayed for 3-6 weeks)
- Requires booster shots every 1-6 months
- Timing and duration of effects requires coordination with behavioral and other interventions
- Not expensive
- Passive Immunization (monoclonal antibodies)
- Pre-formed antibodies are administered
- Dosing ever 3-6 weeks
- Immediate and more predictable effects than active immunization
- Currently expensive

## Medical Basis of Medications	(continued)

- Depot Formulations
- Long-acting (up to 1 month) formulations of current medications to enhance adherence.

## Medical Basis Conclusions	

- Potential Uses of Immunotherapies
- Overdose treatment (with monoclonal antibodies)
- Relapse prevention
- Protection against drug use or in vulnerable populations (*e.g*., fetus)
- Depot medications for relapse prevention

## Medical Basis Recommendation	

**Recommendation 1**
- Support basic immunology studies for increasing the stability and longevity of antibody blood levels for sustained effects.
- Develop combination therapies to simultaneously treat a variety of abused drugs.

## Clinical Trials Considerations

- FDA Clinical Trials Process
- Phase I-IV considerations
- FDA will likely specify the populations and indications.  Examples:
- Overdose is a different indication that relapse
- No medications during pregnancy until proven safe

## Clinical Trials Recommendations

**Recommendation 2****  **
- Since immunotherapy and sustained-release medications will likely be used in off-label situations NIDA should support
**Preclinical studies** addressing the potential safety and efficacy of these medications in vulnerable populations (e.g., pregnant women, fetus, adolescents, etc.).
**Long-term studies** with laboratory animals of different ages, as well as their offspring, before undertaking trials with vulnerable human populations.

## Clinical Trial Recommendations (Continued)

**Recommendation 3**
- NIDA should support studies of the likely extent and nature of off-label medication use
- Including factors and incentives that would promote or retard such use.
- Point out policy options for policy makers to intervene if the patterns of off-label use depart from what is in the best interest of the society.

## Treatment and Financing Issues

- Opportunity to substantially expand treatment.
- Potential to change social views of addiction.
- Challenges for current system.
- Organization
- Philosophy
- Costs
- Privacy
- Discrimination

## Lessons Learned from Previous Pharmacotherapies

- There are lessons to be learned from patient populations being treated for
- Opioids: stigma, NIMBY, patient acceptance, cost
- Alcohol: ideology, system capability, cost, effectiveness . . .
- Nicotine: good patient/clinician acceptance, more effective w psychosocial services, marketing
- These lessons are both positive and negative.

## Treatment and Financing Recommendations

**Recommendation 4**
- NIDA should support studies of potential for patient discrimination due to
- Long-lasting markers in the blood or urine.
- If these markers deters people with drug dependence from accepting immunotherapies.
- False-positive and/or false-negative drug testing.

## Cost  Issues

**Cost:** how much do different formulations and modes of delivery cost?
**Sensitivity to effectiveness:** partial effectiveness may result in different client responses (decreases or even increases in use)
**Cost-effectiveness:** need to compare these therapies to general health using CEA or CBA

## Treatment and Financing Recommendations (continued)

**Recommendation 5 **
- NIDA should support clinical effectiveness studies and financing models that integrate the new pharmacotherapies with psychosocial services in specialty and primary medical care settings.

## Behavioral Responses

- Possible unintended consequences
- Users attempt to overwhelm a partially effective treatment (like low dose methadone)
- Drug substitution: *e.g*., cocaine to METH
- Risk calculations: risk reduction may increase the behavior
- Drug seller behavior: if use of drugs declines sellers might “compete” for market share by price or force

## Behavioral Response Recommendations

**Recommendation 6**
- NIDA should support studies of behavioral consequences such as
- Potential for accidental overdose.
- Changes in drug use patterns include switching drugs, increasing drug dosage or overall consumption.
- Changing the route of administration (*e.g.* nasal to intravenous for greater bioavailability)

## Behavioral Response Recommendations (continued)

**Recommendation 7**
- NIDA should support studies that
- Examine the extent to which the availability of immunotherapy medications might reduce the perceived risk of drug use.
- The effects of such perceptions on drug use behavior in various populations.

## Behavioral Response Recommendations (Continued)

**Recommendation 8**
- NIDA should support studies of the potential effect of immunotherapy medications on illicit drug markets and market-related behaviors.

## Consent and Coerced Treatment

**Vulnerable populations at risk**
- Frequently excluded from clinical trials
- Responses to medications unknown
- Can be pressured to take medications based on inherently coercive setting or circumstances

## Consent and Coerced Treatment, Continued

- Right to determine care
- Legal issues
- Ethical considerations
- Parents may ask to give medication to minor children
- Legal mandates for treatment for competent adults

**Notes:**
Individual’s Right to Determine Care
Legal Issues
	1.	Liberty and privacy protections contained in 5th and 14th Amendment guarantee competent adults the right to determine medical care.
	2.	Informed consent is one of the ways in which this is done for medical care.
	3.	For individuals who are deemed to be not competent (e.g., because of age, mental incapacity, or mental condition) consent has to be gained through a parent or guardian
	4.	This does not preclude the State from coercing individuals to receive treatment, although procedure due process  (advice of counsel, independent review by judge, etc.) and other protections (no experimental treatment, good faith dealing) have been deemed adequate in coerced treatment settings.
	5.	Consequently, persons who are being treated with immunotherapies, once approved by the FDA, should have the right to consent to treamtment.

Ethical Considerations
Respect (e.g., viewing patients/subjects as autonomous agents able to make their own decisions), Beneficience do no harm and maximize benefits), and justice (provide treatment/care equitably) also require that individuals give informed consent.
NIDA and NIAAA guidelines recognize that individuals with drug-use disorders are capable of providing consent
However, a minority of researchers suggest that drug users are not able to give consent, especially when it involves their drugs of choice.
Minors
1.	Children younger than 14 can not consent to treatment; adolescents should be provided the right to ASSENT to treatment.
Parents/guardians able to make 3 kinds of medical decisions for their children:  routine/preventive care, treatment for previously diagnosed problems; and improvement of general and medical well-being.
Third category is most controversial and probably where immunotherapies would fall.  Requires consideration of a number of issues.

## Consent Recommendations

**Recommendation 9**
- NIDA should support studies to clarify procedures and standards to be applied when immunotherapy medications are considered for use in the criminal justice and child welfare systems.
- This includes due process protections when there is a government-imposed treatment requirement.

**Notes:**
Mandated treatment for adults
Adults can be mandated/coerced to receive medical care.
It’s unclear if they can be mandated to a specific treatment, rather than to any treatment
Few guidelines in substance abuse case law; mental health treatment provides some suggestions.
Statements may have to make a finding of incompetency
Government’s right to compel treatment overrides individual’s right to refuse treatment only if s/he is deemed to be dangerous and treatment was deemed by professionals to be in his/her best interest.
Supreme Court (Sells case) recently determined that the treatment offered must be no less intrusive than other available treatments
Bigger consideration/concern may be making treatment available to everyone who needs/wants it.
Also have to worry about potential stigmatization if people are coerced/mandated to receive immunotherapies or sustained-release formulations for drug-use problems.

## Consent Recommendations (Continued)

**Recommendation 10**
- NIDA should support studies to carefully articulate the behavioral, ethical, and social risks associated with treatment of pregnant women and their fetuses and protective therapy in minors.
- Develop clinical practice guidelines for such use or discouragement of such use.

## Major Themes and Issues

- Great need for medications and great promise
- Risk of over-promising, not a “magic bullet”
- Risk from unintended behavioral reactions
- Special problems consent/coercion
- Risks of off-label use
- Some health care systems not ready for these therapies
- Need for new standards of treatment success
- What NIDA can do . . . 10 primary recommendations