Disclaimer
This information collection is a core HTA, i.e. an extensive analysis of one or more health technologies using all nine domains of the HTA Core Model. The core HTA is intended to be used as an information base for local (e.g. national or regional) HTAs.

Use of Intravenous immunoglobulins for Alzeheimer’s disease including Mild Cognitive Impairment

Immunoglobulins (IGG) compared to placebo, not doing anything or Usual supportive care in the treatment of Alzheimer’s disease in elderly AD is diagnosed mostly in people over 65 years of age, although there is an early-onset form that can occur much earlier. According to Wikipedia in 2006, there were 26.6 million sufferers worldwide.

(See detailed scope below)

HTA Core Model Application for Pharmaceuticals (2.0)
Core HTA
Published
Tom Jefferson (Agenas - Italy), Marina Cerbo (Agenas - Italy), Nicola Vicari (Agenas - Italy)
Alessandra Lo Scalzo (Agenas), Anna-Theresa Renner (GOG), Antonio Migliore (Agenas), Ingrid Wilbacher (HVB), Luca Vignatelli (ASSR RER), Luciana Ballini (ASSR RER), Nadine Berndt (CEM), Nicola Vicari (Agenas), Plamen Dimitrov (NCPHA), Susanna Maltoni (ASSR RER), Ricardo Ramos (INFARMED), Tom Jefferson (Agenas)
Agenas - Agenzia nazionale per i servizi sanitari regionali
AAZ (Croatia), ASSR RER (Italy), Avalia-t (Spain), CEM (Luxembourg), GÖG (Austria), HAS (France), HVB (Austria), IER (Slovenia), INFARMED (Portugal), ISC III (Spain), NCPHA (Bulgaria), NIPH (Slovenia), NSPH (Greece), NSPH MD (Romania), SBU (Sweden), SNHTA (Switzerland), THL (Finland), UTA (Estonia).
13.1.2014 12.32.00
30.11.2015 11.18.00
Jefferson T, Cerbo M, Vicari N [eds.]. Use of Intravenous immunoglobulins for Alzeheimer’s disease including Mild Cognitive Impairment [Core HTA], Agenas - Agenzia nazionale per i servizi sanitari regionali ; 2015. [cited 20 September 2021]. Available from: http://corehta.info/ViewCover.aspx?id=267

Use of Intravenous immunoglobulins for Alzeheimer’s disease including Mild Cognitive Impairment

<< Costs and economic evaluationOrganisational aspects >>

Ethical analysis

Authors: Plamen Dimitrov, Anelia Koteva

Summary

IVIG assessment in patients with early Alzheimer’s disease complies with the fundamental ethical principles, as already mentioned. Identified and discussed are the challenges that the use of this technology may provoke for both the patients themselves and their families, on the one hand as well as for the medical staff and the healthcare system management, on the other hand. Part of the problems related to the protection of human dignity of dementia patients could be regulated by some European and international legal documents such as the Charter of Fundamental Rights of the European Union and the Convention for the Protection of Human Rights and Biomedicine, while others, associated with a fair and balanced distribution of health resources for society as a whole, should be addressed and regulated at national/ regional level.

 

Introduction

Due to its prevalence, duration, lack of effective therapy and complex patient care, Alzheimer’s disease has recently become a highly important public health issue. Together with the scientific efforts to clarify the causes of the disease and find the most effective treatment and adequate care for the sick, the researchers seek to better understand the psychological and social impact of the disease on the patients themselves, their families and society as a whole.

 

The ethical analysis aims at providing a balance between norms and values through the discussion of social, political, cultural, legal, religious and economic issues arising from the opposition to the generally accepted societal values, healthcare system goals and the application of new technologies.

 

The present domain focuses on the ethical issues associated with the application of the innovative IVIG technology for the treatment of patients with MCI by debating the following areas:

  • Improving the quality of life of patients;
  • Impaired decision-making competence and freedom of choice/autonomy of patients with MCI;
  • Fair and balanced distribution of resources;
  • Equal access to treatment;
  • Stigmatization.

Methodology

Frame

The collection scope is used in this domain.

TechnologyImmunoglobulins (IGG)
Description

Naturally occurring proteins produced by the body’s immune system to combat foreign antigens

Intended use of the technologyTreatment

Treatment of Alzheimer’s disease

Target condition
Alzheimer’s disease
Target condition description

Alzheimer's disease (AD) or Alzheimer disease, is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death.

Target population

Target population sex: Any. Target population age: elderly. Target population group: Patients who have the target condition.

Target population description

AD is diagnosed mostly in people over 65 years of age, although there is an early-onset form that can occur much earlier. According to Wikipedia in 2006, there were 26.6 million sufferers worldwide. 

Comparisonplacebo, not doing anything or Usual supportive care
Description

There is no MA for IGGs for AD yet and there is no other intervention licensed for use in AD so the comparison would have to be against placebo or best supportive care

Outcomes
  • Description of aims of technology (TECH)
  • Regulatory status (CUR)
  • Cognitive function (EFF)
  • Harms (SAF)
  • Cost effectiveness compared to alternatives (ECO)
  • Potential impact on plasma derivative market (ORG/Medico-legal)
  • Impact on family and carers (SOC)
  • Appropriateness of use in relation to solidity of evidence(ETH)

Assessment elements

TopicIssue RelevantResearch questions or rationale for irrelevance
F0100Beneficence/nonmaleficenceWhat is the severity level of the condition that the technology is directed to?yesWhat is the severity level of the condition that IGG is directed to?
F0010Beneficence/nonmaleficenceWhat are the known and estimated benefits and harms for patients when implementing or not implementing the technology?yesWhat are the known and estimated benefits and harms for patients when implementing or not implementing IGG?
F0011Beneficence/nonmaleficenceWhat are the benefits and harms of the technology for other stakeholders (relatives, other patients, organisations, commercial entities, society, etc.)?yesWhat are the benefits and harms of IGG for other stakeholders (relatives, other patients, organisations, commercial entities, society, etc.)?
F0003Beneficence/nonmaleficenceAre there any other hidden or unintended consequences of the technology and its applications for different stakeholders (patients/users, relatives, other patients, organisations, commercial entities, society etc.)?yesAre there any other hidden or unintended consequences of IGG and its applications for different stakeholders (patients/users, relatives, other patients, organisations, commercial entities, society etc.)?
F0005AutonomyIs the technology used for patients/people that are especially vulnerable?yesIs IGG used for patients/people that are especially vulnerable?
F0004AutonomyDoes the implementation or use of the technology affect the patient´s capability and possibility to exercise autonomy?yesDoes the implementation or use of IGG affect the patient´s capability and possibility to exercise autonomy?
F0006AutonomyIs there a need for any specific interventions or supportive actions concerning information in order to respect patient autonomy when the technology is used?yesIs there a need for any specific IGGs or supportive actions concerning information in order to respect patient autonomy when IGG is used?
F0007AutonomyDoes the implementation or withdrawal of the technology challenge or change professional values, ethics or traditional roles?yesDoes the implementation or withdrawal of IGG challenge or change professional values, ethics or traditional roles?
F0009Respect for personsDoes the implementation or use of the technology affect the user´s moral, religious or cultural integrity?yesDoes the implementation or use of IGG affect the user’s moral, religious or cultural integrity?
F0008Respect for personsDoes the implementation or use of the technology affect human dignity?noThis question is more in the area of legal issues. Implementation of IG do not affect any aspects of human dignity.
F0101Respect for personsDoes the technology invade the sphere of privacy of the patient/user?noEvery technology to some extend is dealing with the privacy of the patients. The current one has much less potential to harm privacy comparing with many others
F0012Justice and EquityHow does implementation or withdrawal of the technology affect the distribution of health care resources?yesHow does implementation or withdrawal of IGG affect the distribution of health care resources?
F0013Justice and EquityHow are technologies with similar ethical issues treated in the health care system?yesHow are technologies with similar ethical issues treated in the health care system?
H0012Justice and EquityAre there factors that could prevent a group or persons to participate?yesAre there factors that could prevent a group or persons to participate?
F0102Ethical consequences of the HTADoes the economic evaluation of the technology contain any ethical problems?yesDoes the economic evaluation of IGG contain any ethical problems?
F0103Ethical consequences of the HTAWhat are the ethical consequences of the assessment of the technology?yesWhat are the ethical consequences of the assessment of IGG?
F0017Ethical consequences of the HTAWhat are the ethical consequences of the choice of end-points, cut-off values and comparators/controls in the assessment?noThis intervention may not have various cut-off values and end-points. Therefore no ethical consequences to consider.
F0014LegislationDoes the implementation or use of the technology affect the realisation of basic human rights?noThis question falls within the scope of Legal domain. Such intervention by our opinion is far from harming basic human rights stated in the UN Universal Declaration of Human Rights
F0016LegislationCan the use of the technology pose ethical challenges that have not been considered in the existing legislations and regulations?no

Methodology description

The Ethical domain has been developed in compliance with the fundamental ethical principles, basically following the method of principalism. Consistently presented are ethical arguments related to the autonomy and benefits for the patient as well as possible complications and limitations pertaining to the implementation of the health technology discussed, without aiming to give a definite answer or “ethical prescription”.

 

The domain comprises 19 issues, preliminarily divided into 4 sections, as listed below:

 

  • Section 1 – Beneficence/Nonmaleficence;
  • Section 2 – Autonomy;
  • Section 3 – Respect for Persons;
  • Section 4 – Justice and Equity.

 

We have answered 14 issues. The other 5 issues we consider either irrelevant or have marked them as a “skipped issue”. More specifically unanswered are:

 

  • Issue 10 (marked as irrelevant);
  • Issue 11 (marked as irrelevant);
  • Issue 17 (marked as irrelevant);
  • Issue 18 (marked as irrelevant);
  • Issue 19 (marked as skipped).

 

 

The object of the analysis is the treatment with intravenous immunoglobulins of patients with early-stage Alzheimer’s disease – an innovative immunotherapy, which is still at the experimental stage.

 

The intravenous immunoglobulin infusions by maintaining optimal level of antibodies in the patient’s organism constitute a form of an experimental passive immunotherapy with a potential for reduction of beta-amyloid plaques, where the technology is expected to help completely heal or significantly improve the cognitive status of the treated subjects with all subsequent benefits, i.e. improved social interaction and quality of life.

 

The object of treatment are adults of both sexes, diagnosed with Alzheimer’s disease at the stage of MCI with an estimate of progression of the disease.

 

Alzheimer’s disease, the most common cause of dementia, belongs to the group of neurodegenerative diseases characterized by unknown etiology, hereditary predisposition and gradual progression over many years. The disease is of great medical and social importance with unnoticeable onset and irreversible course, being incurable at present, leading to death.

Result cards

Beneficence/nonmaleficence

Result card for ETH1: "What is the severity level of the condition that IGG is directed to?"

View full card
ETH1: What is the severity level of the condition that IGG is directed to?
Result

Importance: Unspecified

Transferability: Unspecified

Result card for ETH2: "What are the known and estimated benefits and harms for patients when implementing or not implementing IGG?"

View full card
ETH2: What are the known and estimated benefits and harms for patients when implementing or not implementing IGG?
Result

Importance: Unspecified

Transferability: Unspecified

Result card for ETH3: "What are the benefits and harms of IGG for other stakeholders (relatives, other patients, organisations, commercial entities, society, etc.)?"

View full card
ETH3: What are the benefits and harms of IGG for other stakeholders (relatives, other patients, organisations, commercial entities, society, etc.)?
Result

Importance: Unspecified

Transferability: Unspecified

Result card for ETH4: "Are there any other hidden or unintended consequences of IGG and its applications for different stakeholders (patients/users, relatives, other patients, organisations, commercial entities, society etc.)?"

View full card
ETH4: Are there any other hidden or unintended consequences of IGG and its applications for different stakeholders (patients/users, relatives, other patients, organisations, commercial entities, society etc.)?
Result

Importance: Unspecified

Transferability: Unspecified

Autonomy

Result card for ETH5: "Is IGG used for patients/people that are especially vulnerable?"

View full card
ETH5: Is IGG used for patients/people that are especially vulnerable?
Result

Importance: Unspecified

Transferability: Unspecified

Result card for ETH6: "Does the implementation or use of IGG affect the patient&#180;s capability and possibility to exercise autonomy?"

View full card
ETH6: Does the implementation or use of IGG affect the patient&#180;s capability and possibility to exercise autonomy?
Result

Importance: Unspecified

Transferability: Unspecified

Result card for ETH7: "Is there a need for any specific IGGs or supportive actions concerning information in order to respect patient autonomy when IGG is used?"

View full card
ETH7: Is there a need for any specific IGGs or supportive actions concerning information in order to respect patient autonomy when IGG is used?
Result

Importance: Unspecified

Transferability: Unspecified

Result card for ETH8: "Does the implementation or withdrawal of IGG challenge or change professional values, ethics or traditional roles?"

View full card
ETH8: Does the implementation or withdrawal of IGG challenge or change professional values, ethics or traditional roles?
Result

Importance: Unspecified

Transferability: Unspecified

Respect for persons

Result card for ETH9: "Does the implementation or use of IGG affect the user’s moral, religious or cultural integrity?"

View full card
ETH9: Does the implementation or use of IGG affect the user’s moral, religious or cultural integrity?
Result

Importance: Unspecified

Transferability: Unspecified

Justice and Equity

Result card for ETH10: "How does implementation or withdrawal of IGG affect the distribution of health care resources?"

View full card
ETH10: How does implementation or withdrawal of IGG affect the distribution of health care resources?
Result

Importance: Unspecified

Transferability: Unspecified

Result card for ETH11: "How are technologies with similar ethical issues treated in the health care system?"

View full card
ETH11: How are technologies with similar ethical issues treated in the health care system?
Result

Importance: Unspecified

Transferability: Unspecified

Result card for ETH12 / SOC5: "Are there factors that could prevent a group or persons to participate?"

View full card
ETH12 / SOC5: Are there factors that could prevent a group or persons to participate?
Result

Importance: Unspecified

Transferability: Unspecified

Ethical consequences of the HTA

Result card for ETH13: "Does the economic evaluation of IGG contain any ethical problems?"

View full card
ETH13: Does the economic evaluation of IGG contain any ethical problems?
Result

Importance: Unspecified

Transferability: Unspecified

Result card for ETH14: "What are the ethical consequences of the assessment of IGG?"

View full card
ETH14: What are the ethical consequences of the assessment of IGG?
Result

Importance: Unspecified

Transferability: Unspecified

Discussion

As already stated, the analysis is based on different information sources pointing out that the IVIG innovative health technology is still at the experimental stage. Therefore, the future results of the final stage of the experiment are likely to affect all or some of the ethical considerations already debated on the effectiveness and adequacy of the use of IVIG technology in patients suffering from Alzheimer’s disease in the prodromal MCI stage.

The therapeutic use of the innovative technology faces several ethical challenges. The major issue concerns the respect for the autonomy of the patients with impaired/reduced decision-making capacity, which requires that the engaged healthcare staff demonstrate more correctness and patience towards the sick ones. Moreover, the early stage of Alzheimer’s disease is difficult to diagnose and may sometimes be carrying the risk of false diagnosis, thus resulting in stigmatization and social isolation of patients and their families, which contradicts the ethical principle of nonmaleficence. The third major ethical problem generated by the application of the very technology is associated with the principle of equitable distribution of resources. The use of immunoglobulins for the treatment of patients with Alzheimer’s disease is likely to create a deficit of the same products by reducing the possible therapeutic options for other groups of patients, for whom there is no other alternative treatment.

We believe that the information discussed in the Ethical domain is therefore sufficient to support the process of assessment and the related decision-making process at national/regional level.

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