Prognostic tests for breast cancer recurrence (uPA/PAI-1 [FEMTELLE], MammaPrint, Oncotype DX )

A. Health Problem and Current Use of the Technology

Target Condition

  • CUR1 [from A0001]: Which disease/health problem/potential health problem will Genetic Test be used for?
  • CUR2 [from A0002]: How is the disease/health condition currently being diagnosed? Include a description of any relevant classification system
  • CUR3 [from A0003]: Which are the known risk factors for acquiring the condition?
  • CUR4 [from A0004]: What is the natural course of the condition?
  • CUR5 [from A0005]: What are the symptoms of the disease?
  • CUR6 [from A0006]: What are the consequences of the condition?
  • CUR7 [from A0007]: How many people belong at the moment (will belong) to the specific target group (describe according to sex, age)?
  • CUR8 [from A0008]: What is the burden of disease (mortality, disability, life years lost)?
  • CUR9 [from A0009]: What aspects of the burden of disease are targeted by Genetic Test, i.e. are expected to be reduced by Genetic Test?

Utilisation

  • CUR11 [from A0011]: How much is Genetic Test being used?

Current Management of the Condition

  • CUR22 [from A0013]: How is the disease/health condition currently being diagnosed?
  • CUR13 [from A0014]: According to published algorithms/guidelines (if any), how should the condition be diagnosed?
  • CUR14 [from A0015]: How is the disease/health condition currently being managed?
  • CUR15 [from A0016]: According to published algorithms/guidelines (if any), how should the condition be managed?

Regulatory Status

  • CUR21 [from A0020]: Which approval status has Genetic Test in other countries, or international authorities?

B. Description and technical characteristics of technology

Features of the technology

  • TEC2 [from B0001]: What is the FEMTELLE® uPA/PAI-1 ELISA test?
  • TEC3 [from B0001]: What is the MammaPrint® test?
  • TEC4 [from B0001]: What is the Oncotype DX™ test?
  • TEC5 [from B0002]: Why FEMTELLE®, MammaPrint®, and Oncotype DX™ are used?
  • TEC6 [from B0003]: When FEMTELLE®, MammaPrint®, and Oncotype DX™ were developed or introduced in health care?
  • TEC7 [from B0004]: Who will apply the FEMTELLE®, MammaPrint®, and Oncotype DX™ test?
  • TEC8 [from B0005]: What is the place and context for utilising FEMTELLE®, MammaPrint®, and Oncotype DX™?
  • TEC17 [from B0017]: Is the technology rapidly changing / improving?
  • TEC18 [from B0018]: Are the reference values or cut-off points clearly established?

Investments and tools required to use the technology

  • TEC10 [from B0007]: What material investments are needed to use FEMTELLE®, MammaPrint®, and Oncotype DX™?

Training and information needed for utilizing the technology

  • TEC13 [from B0012]: What kind of qualification, training and quality assurance are needed for the use of FEMTELLE®, MammaPrint®, and Oncotype DX™?
  • TEC14 [from B0014]: What kind of information is needed for the patients receiving FEMTELLE®, MammaPrint®, and Oncotype DX™ and their families?
  • TEC15 [from B0015]: What information do patients outside the target group and the general public need on the use of FEMTELLE®, MammaPrint®, and Oncotype DX™?
  • TEC19 [from B0020]: How does training and quality assurance affect the management or effectiveness?

C. Safety

Patient safety

  • SAF1 [from C0001]: What are the incidence, severity and duration of direct harms to the patient related to the testing and sampling with uPA/PAI-1, Oncotype DX, or MammaPrint®?
  • SAF14 [from C0001]: What are the incidence, severity and duration of psychological harms to the patient related to the testing and with uPA/PAI-1, Oncotype DX, or MammaPrint®?

Occupational safety

  • SAF7 [from C0020]: What kind of occupational harms are there when applying uPA/PAI-1, Oncotype DX, or MammaPrint®?

Environmental safety

  • SAF8 [from C0040]: What kind of environmental risks are there when using uPA/PAI-1, Oncotype DX, or MammaPrint®?

Safety risk management

  • SAF11 [from C0062]: How can one increase safety of patients tested with uPA/PAI-1, Oncotype DX, or MammaPrint® (including technology-, user-, and patient-dependent aspects)?
  • SAF12 [from C0063]: How can one increase safety of professionals applying uPA/PAI-1, Oncotype DX or MammaPrint® (including technology-, user-, and patient-dependent aspects)?

D. Clinical Effectiveness

Change-in management

  • EFF15 [from D0010]: Does the test-treatment chain of uPA/PAI, Mammaprint, or Oncotype for adjuvant therapy reduce or increase the number of women (diagnosed with early stage, invasive breast cancer) requiring hospitalization or hospitalization due side-effects compared to treatment on the basis of the standard practice?
  • EFF6 [from D0021]: Did the results in uPA/PAI, Mammaprint, or Oncotype tests in women diagnosed with early stage invasive breast cancer lead to changes in the treatment choice with adjuvant therapy and/or further imaging compared to the standard practice?
  • EFF7 [from D0023]: Do uPA/PAI, Mammaprint, or Oncotype compared to the standard practice in women diagnosed with early stage invasive breast cancer increase or decrease the probability of adjuvant therapy performed?

Function / HRQL (Health-related quality of life)

  • EFF3 [from D0012]: What is the effect of adjuvant therapy on the basis of uPA/PAI, Mammaprint, or Oncotype test results on health related quality of life compared to treatment on the basis of the standard practice?
  • EFF4 [from D0016]: Does adjuvant therapy on the basis of uPA/PAI, Mammaprint, or Oncotype test results compared to treatment on the basis of the standard practice affect their activities of daily living?

Patient satisfaction

  • EFF5 [from D0017]: Do women diagnosed with early stage, invasive breast cancer feel that the guidance of their adjuvant therapy on the basis of uPA/PAI, Mammaprint, or Oncotype test results was worth it?
  • EFF14 [from D0018]: Would the patient be willing to use the technology (uPA/PAI or Mammaprint or Oncotype test) again?
  • EFF12 [from D0030]: Does the knowledge of the tests results (uPA/PAI, Mammaprint, or Oncotype) improve the patient quality of life in women diagnosed with early stage invasive breast cancer compared to standard practice?

Test-treatment chain

  • EFF9 [from D0025]: What is the effect of adjuvant therapy on the basis of uPA/PAI, Mammaprint, or Oncotype test compared to treatment on the basis of the standard practice in women diagnosed with early stage invasive breast cancer on overall survival and disease specific survival (for example: disease-free-, progression free-, recurrence-free-survival)?
  • EFF13 [from D0032]: How does the treatment with adjuvant therapy on the basis of the test results of uPA/PAI, Mammaprint, or Oncotype compared to treatment on the basis of the standard practice in women diagnosed with early stage invasive breast cancer modify the magnitude and frequency of morbidity?

Morbidity

  • EFF11 [from D0026]: Does adjuvant therapy on the basis of genetic testing results (uPA/PAI, Mammaprint or Oncotype) compared to treatment on the basis of the standard practice in women diagnosed with early stage invasive breast cancer improve patient morbidity?

E. Costs and economic evaluation

Resource utilization

  • ECO1 [from E0001]: What types of resources are used when delivering uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint® and what types of resources are used when delivering standard clinical practice?
  • ECO2 [from E0002]: What quantity of resources is used when delivering uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint® and what quantity of resources are used when delivering standard clinical practice?

Unit costs

  • ECO3 [from E0003]: What are the unit costs of the resources used when delivering uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint® and what are the unit costs of the resources used when delivering standard clinical practice?

Indirect Costs

  • ECO4 [from E0004]: What is the impact of uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint® on indirect costs?

Outcomes

  • ECO5 [from E0005]: What are the incremental effects of uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint® relative to standard clinical practice?

Cost-effectiveness

  • ECO6 [from E0006]: What is the incremental cost-effectiveness ratio of uPA/PAI-1 (Femtelle), OncotypeDx™ or MammaPrint® compared to standard clinical practice?

F. Ethical analysis

Principal questions about the ethical aspects of technology

  • ETH1 [from F0001]: Are uPA/PAI-1, Oncotype or Mammaprint intended to be an, innovative mode of care, an add-on to or modification of a standard mode of care or a replacement of a standard?
  • ETH2 [from F0002]: Can uPA/PAI-1, Oncotype or Mammaprint challenge religious, cultural or moral convictions or beliefs of some groups or change current social arrangements?
  • ETH3 [from F0003]: What can be the hidden or unintended consequences of uPA/PAI-1, Oncotype or Mammaprint and its applications for different stakeholders?

Autonomy

  • ETH4 [from F0005]: Are uPA/PAI-1, Oncotype or Mammaprint used for patients that are especially vulnerable?
  • ETH5 [from F0006]: Can uPA/PAI-1, Oncotype or Mammaprint entail special challenges/risk that the patient/person needs to be informed of?
  • ETH6 [from F0007]: Does the use of uPA/PAI-1, Oncotype or Mammaprint challenge or change professional values, ethics or traditional roles?

Human Dignity

  • ETH7 [from F0008]: Does the implementation or use of uPA/PAI-1, Oncotype or Mammaprint affect human dignity?

Human integrity

  • ETH8 [from F0009]: Does the implementation or use of uPA/PAI-1, Oncotype or Mammaprint affect human integrity?

Beneficence/nonmaleficence

  • ETH9 [from F0010]: What are the benefits and harms for patients, and what is the balance between the benefits and harms when implementing and when not implementing uPA/PAI-1, Oncotype or Mammaprint? Who will balance the risks and benefits in practice and how?
  • ETH10 [from F0011]: Can uPA/PAI-1, Oncotype or Mammaprint harm any other stakeholders? What are the potential benefits and harms for other stakeholders, compared to standard prognostic or predictive factors, what is the balance between them? Who will balance the risks and benefits in practice and how?

Justice and Equity

  • ETH11 [from F0012]: What are the consequences of implementing / not implementing uPA/PAI-1, Oncotype or Mammaprint on justice in the health care system? Are principles of fairness, justness and solidarity respected?
  • ETH12 [from F0013]: How are technologies presenting with relevantly similar (ethical) problems treated in health care system?

Rights

  • ETH13 [from F0014]: Does the implementation or use of uPA/PAI-1, Oncotype or Mammaprint affect the realisation of basic human rights?

Legislation

  • ETH14 [from F0016]: Is legislation and regulation to use Genetic Test fair and adequate?

Questions about effectiveness and accuracy

  • ETH15 [from F0017]: What are the proper end-points for assessment and how should they be investigated?
  • ETH16 [from F0018]: Are the accuracy measures decided and balanced on a transparent and acceptable way?

G. Organisational aspects

Process

  • ORG1 [from G0001]: What work flow and patient flow processes are needed to use the tests (uPA/PAI-1/ Oncotype DX/ MammaPrint) on women with invasive breast cancer?
  • ORG2 [from G0003]: What kind of staff, training and other human resources are required when the tests (uPA/PAI-1/ Oncotype DX/ MammaPrint) are used to support treatment choice?
  • ORG3 [from G0004]: What kind of co-operation and communication of activities have to be mobilised when the tests (uPA/PAI-1/ Oncotype DX/ MammaPrint) are introduced in the clinical pathways of women with invasive breast cancer?

Structure

  • ORG4 [from G0005]: What are the advantages and disadvantages of providing the tests centrally or locally?
  • ORG5 [from G0006]: What kind of investment is needed (equipment, premises, staffing costs, running costs) in order to introduce use of the tests (uPA/PAI-1/ Oncotype DX/ MammaPrint) for women with invasive breast cancer?

Management

  • ORG7 [from G0008]: What management problems and opportunities are attached to use of the tests (uPA/PAI-1/ Oncotype DX/ MammaPrint)?
  • ORG8 [from G0009]: Who decides which women are eligible for the tests and on what basis (e.g. likelihood of cancer recurrence)?

Culture

  • ORG9 [from G0010]: How are the tests (uPA/PAI-1/ Oncotype DX/ MammaPrint) accepted by healthcare professionals and other staff?
  • ORG10 [from G0011]: How should stakeholders (excluding patients/carers, their representative organisations and the public) be taken into account in planning the introduction of the tests (uPA/PAI-1/ Oncotype DX/ MammaPrint)?

H. Social aspects

Major life areas

  • SOC1 [from H0001]: In which social areas (e.g. working life, family life, social relations,…) of the patients may the use of Genetic Test for breast cancer generate change?
  • SOC2 [from H0002]: Who are the important others that the use of Genetic Test for breast cancer may affect in addition to the patient?
  • SOC3 [from H0003]: What kind of support and resources are needed or might be released as Genetic Test (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) is put to use for women with invasive breast cancer?

Individual

  • SOC4 [from H0006]: How do women with invasive breast cancer and important others react and act upon the Genetic Test for breast cancer ?

Communication

  • SOC5 [from H0007]: What is patients' and important others’ knowledge and understanding of Genetic Test for breast cancer?
  • SOC6 [from H0008]: How is the information regarding the use of Genetic Test for breast cancer processed and exchanged?
  • SOC7 [from H0009]: What are the consequences in decision making?

I. Legal aspects

Autonomy of the patient

  • LEG1 [from I0002]: Can patients understand the implications of using/not using Genetic Test for breast cancer?
  • LEG2 [from I0003]: Are there relevant optional technologies that future patients should be allowed to consider?
  • LEG3 [from I0004]: Is it possible to give future patients enough time to consider their decisions?

Privacy of the patient

  • LEG4 [from I0007]: Does the use of Genetic Tests for breast cancer produce some additional (i.e. diagnostically or therapeutically irrelevant) information on the patient?
  • LEG5 [from I0008]: Does the use of Genetic Test for breast cancer produce information that would be relevant for the relatives of the patient?
  • LEG6 [from I0009]: Can the access to the patient data secured properly?
  • LEG7 [from I0010]: What levels of access to which kind of patient information exist in the chain of care?

Equality in health care

  • LEG8 [from I0011]: Are the Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) equally accessible to all women with invasive breast cancer in the society?
  • LEG10 [from I0013]: Is there a wide variation in the acceptability of Genetic Test for breast cancer across Europe?
  • LEG11 [from I0014]: Is health-care tourism expected from/to other European countries?
  • LEG9 [from I0012]: Are the Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) subsidized by the society?

Authorisation & safety

  • LEG12 [from I0015]: Have Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) national/EU level authorisation?
  • LEG13 [from I0016]: Do Genetc Tests for breast cancer need to be listed in a national/EU register?
  • LEG14 [from I0017]: Do Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) fulfill product safety requirements?
  • LEG15 [from I0018]: Do Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) fulfill tissue safety requirements?

Ownership & liability

  • LEG16 [from I0019]: Do Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) infringe some intellectual property right?
  • LEG17 [from I0020]: Does the introduction of Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) presume some additional licensing fees to be paid?
  • LEG18 [from I0021]: What are the width, depth and length of the manufacturers guarantee?
  • LEG19 [from I0022]: Is the user guide of Genetic Test (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) comprehensive enough?

Regulation of the market

  • LEG20 [from I0023]: Are Genetic Tests for beast cancer subject to price control?
  • LEG21 [from I0024]: Are Genetic Tests for breast cancer subject to acquisition regulation?
  • LEG22 [from I0025]: Is the marketing of Genetic Tests for breast cancer to the patients restricted?

Legal regulation of novel/experimental techniques

  • LEG23 [from I0026]: Are Genetic Tests for breast cancer so novel existing legislation was not designed to cover its regulation?
  • LEG24 [from I0027]: How the liability issues are solved according to existing legislation?
  • LEG26 [from I0029]: Is the voluntary participation of patients guaranteed properly?
  • LEG25 [from I0028]: Are new legislative measures needed?

End-user

  • LEG27 [from I0030]: Who is the intended end-user of Genetic Test for breast cancer?
  • LEG28 [from I0031]: Is the use of Genetic Test for breast cancer limited in legislation?
  • LEG29 [from I0032]: Is the health care personnel using Genetic Test for breast cancer according the professional standards?