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

A. Health Problem and Current Use of the Technology

Target Condition

  • CUR1 [from A0002]: What is the disease in the scope of this assessment?
  • CUR2 [from A0003]: What are the known risk factors for the Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI)?
  • CUR3 [from A0004]: What is the natural course of the Alzheimer’s disease (AD) and the Mild Cognitive Impairment (MCI)?
  • CUR4 [from A0005]: What are the symptoms and burden of Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI) for the patient at different stages of the disease?
  • CUR5 [from A0006]: What are the consequences of Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI) for the society (i.e. the burden of the disease)?
  • CUR6 [from A0009]: What aspects of the consequences / burden of disease are targeted by the intravenous immunoglobulin (IVIG) therapy?

Target Population

  • CUR7 [from A0007]: What is the target population in this current assessment of intravenous immunoglobulin (IVIG) therapy?
  • CUR8 [from A0023]: How many people belong to the target population?

Current Management of the Condition

  • CUR9 [from A0017]: What are the differences in the management for the different stages of the Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI)?
  • CUR10 [from A0018]: What are the other typical or common alternatives to intravenous immunoglobulin (IVIG) therapy?
  • CUR11 [from A0024]: How are Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI) currently diagnosed according to published guidelines and in practice?
  • CUR12 [from A0025]: How are the Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI) currently managed according to published guidelines and in practice?

Utilisation

  • CUR13 [from A0001]: For which health conditions and for what purposes are intravenous immunoglobulins (IVIG) used?
  • CUR14 [from A0011]: How much are intravenous immunoglobulins (IVIG) utilised currently and in the future?
  • CUR15 [from A0012]: What kind of variations in the use of intravenous immunoglobulins (IVIG) are there across countries/regions/settings?
  • CUR16 / ORG12 [from G0009]: Who decides which people are eligible for intravenous immunoglobulin (IVIG) therapy and on what basis?
  • CUR17 / TEC3 [from B0003]: What is the phase of development and implementation of intravenous immunoglobulins (IVIG)?
  • CUR18 [from F0001]: Is intravenous immunoglobulin (IVIG) therapy a new, innovative mode of care, an add-on to or modification of a standard mode of care or replacement of a standard mode of care?

Regulatory Status

  • CUR19 [from A0020]: What is the marketing authorisation status of intravenous immunoglobulins (IVIG)?
  • CUR20 [from A0021]: What is the reimbursement status of intravenous immunoglobulins (IVIG) across countries?

B. Description and technical characteristics of technology

Features of the technology

  • TEC1a [from B0001]: What are Intravenous Inmunoglobulins (IVIG)?
  • TEC1b [from B0001]: What are the potential comparators for IVIG use in Alzheimer’s disease and Mild Cognitive Impairment?
  • TEC2 [from B0002]: What is the approved indication and claimed benefit of IVIG?
  • CUR17 / TEC3 [from B0003]: What is the phase of development and implementation of intravenous immunoglobulins (IVIG)?
  • TEC4 [from B0004]: Who performs or administers IVIG?
  • TEC5 [from B0005]: In what context and level of care are IVIG used?

Other

  • TEC6 [from A0022]: Who manufactures IVIG?

Investments and tools required to use the technology

  • TEC7 [from B0007]: What material investments are needed to use IVIG?
  • TEC8 [from B0008]: What kind of special premises are needed to use IVIG?
  • TEC9 [from B0009]: What equipment and supplies are needed to use IVIG?
  • TEC10 [from B0010]: What kind of data and records are needed to monitor the use of IVIG ?
  • TEC11 [from B0011]: What kind of registers are needed to monitor the use IVIG?

Training and information needed to use the technology

  • TEC12 [from B0012]: What kind of qualification and quality assurance processes are needed for the use or maintenance of IVIG?
  • TEC13 [from B0013]: What kind of training and information is needed for the personnel/carer using IVIG?
  • TEC14 [from B0014]: What kind of training and information should be provided for the patients who uses IVIG o for their families?

C. Safety

Patient safety

  • SAF1 [from C0001]: What is the frequency of immediate and delayed serious and non-serious adverse events in patients with Mild Cognitive Impairment and in patients with Alzheimer’s disease treated with IVIG?
  • SAF2 [from C0002]: Do the incidence and severity of adverse events of IVIG change with different dosing and administration schemes when used in patients with Mild Cognitive Impairment or Alzheimer’s disease?
  • SAF3 [from C0008]: What are the incidence, severity and duration of adverse events when compared with placebo or with drugs approved (acetylcholinesterase inhibitors, memantine) for the treatment of Alzheimer’s disease?
  • SAF4 [from C0007]: Do IVIG interfere with or are affected by other treatments used in patients with Mild Cognitive Impairment or in patients with Alzheimer’s disease?

Safety risk management

  • SAF5 [from C0060]: Does the safety profile of IVIG vary according to mode of production or between different IVIG approved versions or products when used in patients with Mild Cognitive Impairment and Alzheimer’s disease?

D. Clinical Effectiveness

Morbidity

  • EFF1a [from D0006]: Are IVIG effective in slowing or avoiding progression from Mild Cognitive Impairment to Alzheimer’s disease when compared to placebo?
  • EFF1b [from D0006]: Are IVIG effective in improving biomarkers of progression from Mild Cognitive Impairment to Alzheimer’s disease when compared to placebo?
  • EFF1c [from D0006]: Are IVIG effective in improving imaging markers of progression from Mild Cognitive Impairment to Alzheimer’s disease when compared to placebo?
  • EFF1d [from D0006]: Are IVIG effective in slowing disease progression from mild-to-moderate to moderate-to-severe Alzheimer’s disease (measured with MMSE) when compared to placebo or acetyl cholinesterase inhibitors?
  • EFF1e [from D0006]: Are IVIG effective in improving biomarkers of progression in patients with mild-to-moderate Alzheimer’s disease when compared to placebo or acetyl cholinesterase inhibitors?
  • EFF1f [from D0006]: Are IVIG effective in improving imaging markers of progression in patients with mild-to-moderate Alzheimer’s disease when compared to placebo or acetyl cholinesterase inhibitors?
  • EFF1g [from D0006]: Are IVIG effective in improving biomarkers of progression in patients with moderate-to-severe Alzheimer’s disease when compared to placebo or memantine?
  • EFF1h [from D0006]: Are IVIG effective in improving imaging markers of progression in patients with moderate-to-severe Alzheimer’s disease when compared to placebo or memantine?
  • EFF2a [from D0005]: Are IVIG effective in improving neuropsychiatric symptoms in patients Mild Cognitive Impairment when compared to placebo?
  • EFF2b [from D0005]: Are IVIG effective in improving behavioural symptoms in patients with mild-to-moderate Alzheimer’s disease when compared to placebo or acetyl cholinesterase inhibitors?
  • EFF2c [from D0005]: Are IVIG effective in improving behavioural symptoms in patients with moderate-to-severe Alzheimer’s disease when compared to placebo or memantine?

Mortality

  • EFF3a [from D0001]: Are IVIG effective in reducing overall mortality in patients with Mild Cognitive Impairment when compared to placebo?
  • EFF3b [from D0001]: Are IVIG effective in reducing overall mortality in patients with mild-to-moderate Alzheimer’s disease when compared to placebo or acetyl cholinesterase inhibitors?
  • EFF3c [from D0001]: Are IVIG effective in reducing overall mortality in patients with moderate-to-severe Alzheimer’s disease when compared to placebo or memantine?

Function

  • EFF4a [from D0011]: Are IVIG effective in improving cognitive functions of patients with Mild Cognitive Impairment when compared to placebo?
  • EFF4b [from D0011]: Are IVIG effective in improving cognitive functions of patients with mild-to-moderate Alzheimer’s disease when compared to placebo or acetyl cholinesterase inhibitors?
  • EFF4c [from D0011]: Are IVIG effective in improving cognitive functions of patients with moderate-to-severe Alzheimer’s disease when compared to placebo or memantine?
  • EFF5a [from D0016]: Are IVIG effective in improving activities of daily living of patients with mild-to-moderate Alzheimer’s disease when compared to placebo or acetyl cholinesterase inhibitors?
  • EFF5b [from D0016]: Are IVIG effective in improving activities of daily living of patients with moderate-to-severe Alzheimer’s disease when compared to placebo or memantine?

Health-related Quality of life

  • EFF6a [from D0012]: Are IVIG effective in improving generic health-related quality of life of patients with Mild Cognitive Impairment when compared to placebo?
  • EFF6b [from D0012]: Are IVIG effective in improving generic health-related quality of life of patients with mild-to-moderate Alzheimer’s disease when compared to placebo or acetyl cholinesterase inhibitors?
  • EFF6c [from D0012]: Are IVIG effective in improving generic health-related quality of life of caregivers of patients with mild-to-moderate Alzheimer’s disease when compared to placebo or acetyl cholinesterase inhibitors?
  • EFF6d [from D0012]: Are IVIG effective in improving generic health-related quality of life of caregivers of patients with moderate-to-severe Alzheimer’s disease when compared to placebo or memantine?
  • EFF7a [from D0013]: Are IVIG effective in improving disease specific health-related quality of life of patients with mild-to- moderate Alzheimer’s disease when compared to placebo or acetyl cholinesterase inhibitors?
  • EFF7b [from D0013]: Are IVIG effective in improving disease specific health-related quality of life of caregivers of patients with mild-to-moderate Alzheimer’s disease when compared to placebo or acetyl cholinesterase inhibitors?
  • EFF7c [from D0013]: Are IVIG effective in improving disease specific health-related quality of life of caregivers of patients with moderate-to-severe Alzheimer’s disease when compared to placebo or memantine?

Change-in management

  • EFF8a [from D0010]: Does IVIG impact on the need for hospitalization in patients with mild-to-moderate Alzheimer’s disease when compared to placebo or acetyl cholinesterase inhibitors?
  • EFF8b [from D0010]: Does IVIG impact on the need for institutionalization in patients with mild-to-moderate Alzheimer’s disease when compared to placebo or acetyl cholinesterase inhibitors?
  • EFF8c [from D0010]: Does IVIG impact on the need for hospitalization in patients with moderate-to-severe Alzheimer’s disease when compared to placebo or memantine?
  • EFF8d [from D0010]: Does IVIG impact on the need for institutionalization in patients with moderate-to-severe Alzheimer’s disease when compared to placebo or memantine?

Benefit-harm balance

  • EFF9a [from D0029]: What are the overall benefits and harms of IVIG in health outcomes of patients with Mild Cognitive Impairment?
  • EFF9b [from D0029]: What are the overall benefits and harms of IVIG in health outcomes of patients with mild-to-moderate Alzheimer’s disease?
  • EFF9c [from D0029]: What are the overall benefits and harms of IVIG in health outcomes of patients with moderate-to-severe Alzheimer’s disease?

E. Costs and economic evaluation

Resource utilization

  • ECO1 [from E0001]: What types of resources are used when delivering IGG and its comparators (resource-use identification)?
  • ECO2 [from E0002]: What amounts of resources are used when delivering IGG and its comparators (resource-use measurement)?
  • ECO3 [from E0009]: What were the measured and/or estimated costs of IGG and its comparator(s) (resource-use valuation)?

Measurement and estimation of outcomes

  • ECO4 [from E0005]: What is(are) the measured and/or estimated health-related outcome(s) of IGG and its comparator(s)?

Examination of costs and outcomes

  • ECO5 [from E0006]: What are the estimated differences in costs and outcomes between IGG and its comparator(s)?

Characterising uncertainty

  • ECO6 [from E0010]: What are the uncertainties surrounding the costs and economic evaluation(s) of IGG and its comparator(s)?

Characterising heterogeneity

  • ECO7 [from E0011]: To what extent can differences in costs, outcomes, or ‘cost effectiveness’ be explained by variations between any subgroups using IGG and its comparator(s)?

Validity of the model(s)

  • ECO8 [from E0012]: To what extent can the estimates of costs, outcomes, or economic evaluation(s) be considered as providing valid descriptions of IGG and its comparator(s)?

F. Ethical analysis

Beneficence/nonmaleficence

  • ETH1 [from F0100]: What is the severity level of the condition that IGG is directed to?
  • ETH2 [from F0010]: What are the known and estimated benefits and harms for patients when implementing or not implementing IGG?
  • ETH3 [from F0011]: What are the benefits and harms of IGG for other stakeholders (relatives, other patients, organisations, commercial entities, society, etc.)?
  • ETH4 [from F0003]: 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.)?

Autonomy

  • ETH5 [from F0005]: Is IGG used for patients/people that are especially vulnerable?
  • ETH6 [from F0004]: Does the implementation or use of IGG affect the patient´s capability and possibility to exercise autonomy?
  • ETH7 [from F0006]: Is there a need for any specific IGGs or supportive actions concerning information in order to respect patient autonomy when IGG is used?
  • ETH8 [from F0007]: Does the implementation or withdrawal of IGG challenge or change professional values, ethics or traditional roles?

Respect for persons

  • ETH9 [from F0009]: Does the implementation or use of IGG affect the user’s moral, religious or cultural integrity?

Justice and Equity

  • ETH10 [from F0012]: How does implementation or withdrawal of IGG affect the distribution of health care resources?
  • ETH11 [from F0013]: How are technologies with similar ethical issues treated in the health care system?
  • ETH12 / SOC5 [from H0012]: Are there factors that could prevent a group or persons to participate?

Ethical consequences of the HTA

  • ETH13 [from F0102]: Does the economic evaluation of IGG contain any ethical problems?
  • ETH14 [from F0103]: What are the ethical consequences of the assessment of IGG?

G. Organisational aspects

Health delivery process

  • ORG1 [from G0001]: How does IGG affect the current work processes?
  • ORG2 [from G0100]: What kind of patient/participant flow is associated with IGG?
  • ORG3 [from G0002]: What kind of involvement has to be mobilized for patients/participants and important others?
  • ORG4 [from G0003]: What is the process ensuring proper education and training of the staff?
  • ORG5 [from G0004]: What kind of co-operation and communication of activities have to be mobilised?
  • ORG6 [from G0012]: How is the quality assurance and monitoring system of IGG organised?

Structure of health care system

  • ORG7 [from G0005]: How does de-centralisation or centralization requirements influence the implementation of IGG?
  • ORG8 [from G0101]: What are the processes ensuring access to care of IGG for patients/participants?

Process-related costs

  • ORG9 [from G0006]: What are the processes related to purchasing and setting up IGG?
  • ORG10 [from G0007]: What are the likely budget impacts of implementing the technologies being compared?

Management

  • ORG11 [from G0008]: What management problems and opportunities are attached to IGG?
  • CUR16 / ORG12 [from G0009]: Who decides which people are eligible for intravenous immunoglobulin (IVIG) therapy and on what basis?

Culture

  • ORG13 [from G0010]: How is IGG accepted?
  • ORG14 [from G0011]: How are the other interest groups taken into account in the planning / implementation of IGG?

H. Social aspects

Individual

  • SOC1 [from H0100]: What kind of changes do patients or citizens expect?
  • SOC2 [from H0002]: Who are the important others that may be affected, in addition to the individual using IGG?
  • SOC3 [from H0004]: What kind of changes may the use of IGG generate in the individual's role in the major life areas?
  • SOC4 [from H0006]: How do patients, citizens and the important others using IGG react and act upon IGG?
  • ETH12 / SOC5 [from H0012]: Are there factors that could prevent a group or persons to participate?

Major life areas

  • SOC6 [from H0001]: Which social areas does the use of IGG influence?
  • SOC7 [from H0009]: What influences patients’ or citizens’ decisions to use IGG?