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.

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

UPA/PAI-1 (FEMTELLE), MammaPrint, Oncotype DX compared to Standard of care in selecting treatment for Breast cancer recurrence in females

(See detailed scope below)

HTA Core Model Application for Diagnostic Technologies (1.1)
Core HTA
Published
Tom Jefferson (age.na.s, Italy), Nicola Vicari (age.na.s, Italy), Heike Raatz (SNHTA, Switzerland)
Sarah Baggaley, NICE (Health problem and current use); Antonio Migliore, Agenas (Description and technical characteristics); Iris Pasternack, THL-FINOHTA (Safety); Mirjana Huic, AAZ (Clinical effectiveness), Isaura Vieira, INFARMED (Costs and economic evaluation); Dario Sacchini, A.Gemelli (Ethical analysis); Jennifer Butt, NICE (Organisational aspects); Marco Marchetti, A.Gemelli (Social and Legal aspects)
Agenzia nationale per i servizi sanitari regionali (age.na.s), Italy
A. Gemelli (Italy), AAZ (Croatia), Agenas (Italy), AHTAPol (Poland), AVALIA-t (Spain), INFARMED (Portugal), IPH-RS (Slovenia), NICE (United Kingdom), Regione Veneto (Italy), SNHTA (Switzerland), THL (Finland), UMIT (Austria)
13.6.2011 14.00.00
31.1.2013 18.05.00
Jefferson T, Vicari N, Raatz H [eds.]. Prognostic tests for breast cancer recurrence (uPA/PAI-1 [FEMTELLE], MammaPrint, Oncotype DX ) [Core HTA], Agenzia nationale per i servizi sanitari regionali (age.na.s), Italy ; 2013. [cited 24 October 2021]. Available from: http://corehta.info/ViewCover.aspx?id=113

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

<< Social aspectsCollection appendices >>

Authors: Marina Casini, Emanuela Midolo, Marco Marchetti

Summary

Analysis of legal aspects highlighted three points that, in our opinion, have shortcomings and should be developed at the European level:

1) the lack of an ad hoc European directive on medical devices —in vitro predictive tests. In fact, in our analysis we could not refer to specific EC legislation, but we referred, by analogy, to other documents such as the Directive 98/79 EC on in vitro diagnostic medical devices.

2) the absence of the FEMTELLE® uPA/PAI-1 test, MammaPrint® and Oncotype DX® from the Eudamed register (European registry). This registration is important in order to improve control of sales, use and movement within the EC of such tests.

3) the need to ensure equitable access to these tests, if their clinical utility and validity is confirmed by good quality evidence. This point is especially important particularly in respect of the principle of "equitable access to care", included in most of the European conventions.

Introduction

Legal issues related to prognostic tests for breast cancer are discussed in this domain. Some issues are directly related to the patient and his/her basic rights, such as autonomy, informed consent, privacy and confidentiality. Other issues are linked to the technology, such as authorisations, patents/licenses, acquisition process, price and reimbursement regulations, product safety, guarantee and liability. Some assessment elements in this domain were considered not relevant and they were not translated into research questions.

The analysis of legal aspects was carried out at a European level, so regulations and documents of the European Union and Council of Europe were taken into account.

Methodology

Frame

The collection scope is used in this domain.

TechnologyuPA/PAI-1 (FEMTELLE), MammaPrint, Oncotype DX
Description

Urokinase plasminogen activator /plasminogen activator inhibitor 1 ELISA (uPA/PAI-1) is a registered enzyme-linked immunoassay (ELISA) kit (FEMTELLE) for the analysis of uPA/PAI-1 in fresh frozen tissue and is being provided by American Diagnostica Inc. It is CE marked in Europe but for research use only in the USA. Other commercial ELISA kits for separate in-house analysis of uPA and/or PAI-1 are available from different suppliers. These also use samples other than tissue and are also used for indications other than cancer {1}.

Technical details:

- Inspection of unfixed tissue

- Removal of a representative piece of tumour tissue (>50 mg)

- Freezing of the unfixed tissue (-20°C or colder)

- Storage of the frozen tissue (-20°C or colder) possible up to 3 weeks

Clinical Laboratory (Pathology, Hospital)

- Transport of frozen tumour tissue on dry ice

- Extraction of uPA and PAI-1

- Perform FEMTELLE uPA/PAI-1 ELISA

- Transfer of test results to physician

Costs for FEMTELLE including preparation, shipping and analysis of samples in a qualified laboratory amount to €400 (http://www.hkk.de/info/aktuelles/brustkrebs_tumorprognosetest). In house analysis with separate ELISA kits costs about €200.

Possible logistic issues to consider are {2}:

- Relatively large samples are needed. Given that the mean tumour size is <2 cm in many centres, this means that a substantial part of the tissue may be lacking for light microscopic investigation.

- Many centres no longer routinely freeze breast tissue and therefore lack the expensive equipment for this process.

Oncotype DX (Genomic Health) quantifies gene expression for 21 genes in breast cancer tissue by real-time reverse transcriptase-polymerase chain reaction (RT-PCR).

MammaPrint (Agendia) is a gene expression profiling platform based on microarray technology which uses a 70-gene expression profile {3}. The sample studied is fresh or frozen tissue. It has received 510(k) clearance from the FDA (premarket notification for medical devices), which also covers the use of Asuragen's RNARetain®, a room temperature, molecular fixative that supersedes freezing the tissue before shipment to the central US laboratory (www.agendia.com).

The test requires a fresh sample of tissue  composed of a minimum of 30% malignant cells and must be received by the company in their kit within 5 days of obtaining the material. The MammaPrint assay was developed on the basis of research initially conducted at the Netherlands Cancer Institute (Amsterdam) and collaborating institutions. Primary tumours from 117 patients with axillary lymph node-negative primary breast cancer were analysed on oligonucleotide microarrays. The data were subjected to supervised classification to establish a 70-gene RNA expression profile that correlated with a relatively short interval to distant metastases. [from NICE protocol and ASCO guideline]

Oncotype DX and MammaPrint have been evaluated and large-scale studies (TAILORx and MINDACT) are underway. The German Working Group for Gynecological Oncology1 (AGO) and the American Society of Clinical Oncology (ASCO) have recommended uPA/PAI-1 as risk-group-classification markers for routine clinical decision making in node-negative breast cancer, alongside established clinical and histomorphological factors.

Oncotype DX is recommended for node negative, oestrogen receptor-positive women and MammaPrint is applied in all early breast cancers. The tests are expensive: MammaPrint costs €2675 and Oncotype DX, US $3400.

RT-PCR and microarray analysis usually cost US $3500 or more. Oncotype and MammaPrint are not routinely covered by German statutory health insurance. MammaPrint is covered by Medicare and Medicaid in the USA (Pharmacogenomics Reporter: 23 December 2009; www.genomeweb.com.)

MeSH Terms:

There are no MeSH-Terms for Oncotype DX and MammaPrint.

Intended use of the technologyDefining an existing health condition in further detail to assist selection of appropriate or optimal treatment

Assessment of risk of breast cancer recurrence

Target condition
Breast cancer recurrence
Target condition description

Assessment of risk of breast cancer recurrence and likelihood of benefit from adjuvant treatment (particularly chemotherapy).

As testing for oestrogen receptor positivity is already considered to be part of the standard of care using these tests to decide on adjunctive treatment with Tamoxifen will not be considered part of the study question.

Target population

Target population sex: Female. Target population age: Any age except fetuses. Target population group: Patients who have the target condition.

Target population description

Women with invasive breast cancer in whom adjunctive treatment might be indicated

ComparisonStandard of care
Description

Standard care without any of the three index tests (uPA/PAI-1, MammaPrint, Oncotype DX).

Depending on manpower and time resources the three index tests may also be compared with each other.

Assessment elements

TopicIssue RelevantResearch questions or rationale for irrelevance
I0002Autonomy of the patientCan patients understand the implications of using/not using the technology?yesCan patients understand the implications of using/not using Genetic Test for breast cancer?
I0003Autonomy of the patientAre there relevant optional technologies that future patients should be allowed to consider?yesAre there relevant optional technologies that future patients should be allowed to consider?
I0004Autonomy of the patientIs it possible to give future patients enough time to consider their decisions?yesIs it possible to give future patients enough time to consider their decisions?
I0005Autonomy of the patientIs it possible to obtain an advance directive on the use of the technology?noNot applicable for genetic tests.
I0009Privacy of the patientCan the access to the patient data secured properly?yesCan the access to the patient data secured properly?
I0010Privacy of the patientWhat levels of access to which kind of patient information exist in the chain of care?yesWhat levels of access to which kind of patient information exist in the chain of care?
I0007Privacy of the patientDoes the use of the technology produce some additional (i.e. diagnostically or therapeutically irrelevant) information on the patient?yesDoes the use of Genetic Tests for breast cancer produce some additional (i.e. diagnostically or therapeutically irrelevant) information on the patient?
I0008Privacy of the patientDoes the use of the technology produce information that would be relevant for the relatives of the patient?yesDoes the use of Genetic Test for breast cancer produce information that would be relevant for the relatives of the patient?
I0033Privacy of the patientDoes the use of the technology produce such information on the patient that is not directly relevant to the current disease/condition?noIt is incorporated in question I0007.
I0011Equality in health careIs the technology equally accessible to all needing members in a given society?yesAre the Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) equally accessible to all women with invasive breast cancer in the society?
I0012Equality in health careIs the technology subsidized by the society?yesAre the Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) subsidized by the society?
I0013Equality in health careIs there a wide variation in the acceptability of the technology across Europe?yesIs there a wide variation in the acceptability of Genetic Test for breast cancer across Europe?
I0014Equality in health careIs health-care tourism expected from/to other European countries?yesIs health-care tourism expected from/to other European countries?
I0015Authorisation & safetyHas the technology national/EU level authorisation?yesHave Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) national/EU level authorisation?
I0016Authorisation & safetyDoes the technology need to be listed in a national/EU register?yesDo Genetc Tests for breast cancer need to be listed in a national/EU register?
I0017Authorisation & safetyDoes the technology fulfil product safety requirements?yesDo Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) fulfill product safety requirements?
I0018Authorisation & safetyDoes the technology fulfil tissue safety requirements?yesDo Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) fulfill tissue safety requirements?
I0019Ownership & liabilityDoes the technology infringe some intellectual property right?yesDo Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) infringe some intellectual property right?
I0020Ownership & liabilityDoes the introduction of the technology presume some additional licensing fees to be paid?yesDoes the introduction of Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) presume some additional licensing fees to be paid?
I0021Ownership & liabilityWhat are the width, depth and length of the manufacturers guarantee?yesWhat are the width, depth and length of the manufacturers guarantee?
I0022Ownership & liabilityIs the user guide of the technology comprehensive enough?yesIs the user guide of Genetic Test (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) comprehensive enough?
I0023Regulation of the marketIs the technology subject to price control?yesAre Genetic Tests for beast cancer subject to price control?
I0024Regulation of the marketIs the technology subject to acquisition regulation?yesAre Genetic Tests for breast cancer subject to acquisition regulation?
I0025Regulation of the marketIs the marketing of the technology to the patients restricted?yesIs the marketing of Genetic Tests for breast cancer to the patients restricted?
I0026Legal regulation of novel/experimental techniquesIs the technology so novel existing legislation was not designed to cover its regulation?yesAre Genetic Tests for breast cancer so novel existing legislation was not designed to cover its regulation?
I0027Legal regulation of novel/experimental techniquesHow the liability issues are solved according to existing legislation?yesHow the liability issues are solved according to existing legislation?
I0028Legal regulation of novel/experimental techniquesAre new legislative measures needed?yesAre new legislative measures needed?
I0029Legal regulation of novel/experimental techniquesIs the voluntary participation of patients guaranteed properly?yesIs the voluntary participation of patients guaranteed properly?
I0030End-userWho is the intended end-user of the technology?yesWho is the intended end-user of Genetic Test for breast cancer?
I0031End-userIs the use of the technology limited in legislation?yesIs the use of Genetic Test for breast cancer limited in legislation?
I0032End-userIs the health care personnel using the technology according the professional standards?yesIs the health care personnel using Genetic Test for breast cancer according the professional standards?

Methodology description

Information sources

Legal aspects of prognostic tests for breast cancer were analysed from legal texts in the European area.

Our work is based on finding the main sources of European regulations. This is a large, complex and varied biojuridical material formed within the European Union and Council of Europe. The documentation is diversified in terms of cogency (some documents have binding authority, others simply address) and origins (different bodies of enactment). However, unless more or less detail, we found common elements in the discipline of information and consent, privacy protection, and access to treatment.

Result cards

Autonomy of the patient

Result card for LEG1: "Can patients understand the implications of using/not using Genetic Test for breast cancer?"

View full card
LEG1: Can patients understand the implications of using/not using Genetic Test for breast cancer?
Method
Result

Importance: Important

Transferability: Completely

Result card for LEG2: "Are there relevant optional technologies that future patients should be allowed to consider?"

View full card
LEG2: Are there relevant optional technologies that future patients should be allowed to consider?
Method
Result

Importance: Important

Transferability: Completely

Result card for LEG3: "Is it possible to give future patients enough time to consider their decisions?"

View full card
LEG3: Is it possible to give future patients enough time to consider their decisions?
Method
Result

Importance: Important

Transferability: Completely

Privacy of the patient

Result card for LEG6: "Can the access to the patient data secured properly?"

View full card
LEG6: Can the access to the patient data secured properly?
Method
Result

Importance: Important

Transferability: Completely

Result card for LEG7: "What levels of access to which kind of patient information exist in the chain of care?"

View full card
LEG7: What levels of access to which kind of patient information exist in the chain of care?
Method
Result

Importance: Important

Transferability: Completely

Result card for LEG4: "Does the use of Genetic Tests for breast cancer produce some additional (i.e. diagnostically or therapeutically irrelevant) information on the patient?"

View full card
LEG4: Does the use of Genetic Tests for breast cancer produce some additional (i.e. diagnostically or therapeutically irrelevant) information on the patient?
Method
Result

Importance: Important

Transferability: Completely

Result card for LEG5: "Does the use of Genetic Test for breast cancer produce information that would be relevant for the relatives of the patient?"

View full card
LEG5: Does the use of Genetic Test for breast cancer produce information that would be relevant for the relatives of the patient?
Method
Result

Importance: Important

Transferability: Completely

Equality in health care

Result card for LEG8: "Are the Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) equally accessible to all women with invasive breast cancer in the society?"

View full card
LEG8: Are the Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) equally accessible to all women with invasive breast cancer in the society?
Method
Result

Importance: Important

Transferability: Completely

Result card for LEG9: "Are the Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) subsidized by the society?"

View full card
LEG9: Are the Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) subsidized by the society?
Method
Result
Comment

Importance: Important

Transferability: Completely

Result card for LEG10: "Is there a wide variation in the acceptability of Genetic Test for breast cancer across Europe?"

View full card
LEG10: Is there a wide variation in the acceptability of Genetic Test for breast cancer across Europe?
Method
Result

Importance: Important

Transferability: Completely

Result card for LEG11: "Is health-care tourism expected from/to other European countries?"

View full card
LEG11: Is health-care tourism expected from/to other European countries?
Method
Result

Importance: Important

Transferability: Completely

Authorisation & safety

Result card for LEG12: "Have Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) national/EU level authorisation?"

View full card
LEG12: Have Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) national/EU level authorisation?
Method
Result

Importance: Important

Transferability: Completely

Result card for LEG13: "Do Genetc Tests for breast cancer need to be listed in a national/EU register?"

View full card
LEG13: Do Genetc Tests for breast cancer need to be listed in a national/EU register?
Method
Result
Comment

Importance: Important

Transferability: Completely

Result card for LEG14: "Do Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) fulfill product safety requirements?"

View full card
LEG14: Do Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) fulfill product safety requirements?
Method
Result

Importance: Important

Transferability: Completely

Result card for LEG15: "Do Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) fulfill tissue safety requirements?"

View full card
LEG15: Do Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) fulfill tissue safety requirements?
Method
Result

Importance: Important

Transferability: Completely

Ownership & liability

Result card for LEG16: "Do Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) infringe some intellectual property right?"

View full card
LEG16: Do Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) infringe some intellectual property right?
Method
Result

Importance: Optional

Transferability: Partially

Result card for LEG17: "Does the introduction of Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) presume some additional licensing fees to be paid?"

View full card
LEG17: Does the introduction of Genetic Tests (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) presume some additional licensing fees to be paid?
Method
Result

Importance: Critical

Transferability: Completely

Result card for LEG18: "What are the width, depth and length of the manufacturers guarantee?"

View full card
LEG18: What are the width, depth and length of the manufacturers guarantee?
Method
Result

Importance: Optional

Transferability: Completely

Result card for LEG19: "Is the user guide of Genetic Test (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) comprehensive enough?"

View full card
LEG19: Is the user guide of Genetic Test (uPA/PAI-1 ELISA/ Oncotype DX/ MammaPrint) comprehensive enough?
Method
Result

Importance: Important

Transferability: Completely

Regulation of the market

Result card for LEG20: "Are Genetic Tests for beast cancer subject to price control?"

View full card
LEG20: Are Genetic Tests for beast cancer subject to price control?
Method
Result

Importance: Important

Transferability: Completely

Result card for LEG21: "Are Genetic Tests for breast cancer subject to acquisition regulation?"

View full card
LEG21: Are Genetic Tests for breast cancer subject to acquisition regulation?
Method
Result

Importance: Important

Transferability: Not

Result card for LEG22: "Is the marketing of Genetic Tests for breast cancer to the patients restricted?"

View full card
LEG22: Is the marketing of Genetic Tests for breast cancer to the patients restricted?
Method
Result

Importance: Important

Transferability: Completely

Legal regulation of novel/experimental techniques

Result card for LEG23: "Are Genetic Tests for breast cancer so novel existing legislation was not designed to cover its regulation?"

View full card
LEG23: Are Genetic Tests for breast cancer so novel existing legislation was not designed to cover its regulation?
Method
Result

Importance: Critical

Transferability: Completely

Result card for LEG24: "How the liability issues are solved according to existing legislation?"

View full card
LEG24: How the liability issues are solved according to existing legislation?
Method
Result

Importance: Important

Transferability: Completely

Result card for LEG25: "Are new legislative measures needed?"

View full card
LEG25: Are new legislative measures needed?
Method
Result
Comment

Importance: Critical

Transferability: Completely

Result card for LEG26: "Is the voluntary participation of patients guaranteed properly?"

View full card
LEG26: Is the voluntary participation of patients guaranteed properly?
Method
Result

Importance: Important

Transferability: Completely

End-user

Result card for LEG27: "Who is the intended end-user of Genetic Test for breast cancer?"

View full card
LEG27: Who is the intended end-user of Genetic Test for breast cancer?
Method
Result

Importance: Optional

Transferability: Unspecified

Result card for LEG28: "Is the use of Genetic Test for breast cancer limited in legislation?"

View full card
LEG28: Is the use of Genetic Test for breast cancer limited in legislation?
Method
Result

Importance: Critical

Transferability: Completely

Result card for LEG29: "Is the health care personnel using Genetic Test for breast cancer according the professional standards?"

View full card
LEG29: Is the health care personnel using Genetic Test for breast cancer according the professional standards?
Method
Result

Importance: Important

Transferability: Completely

Discussion

We found a range of documents, varying in nature and origin, published by  European Union bodies about issues and profiles that are not directly related to the prognostic tests in question, but on general areas of the doctor-patient relationship, on information and consent, and on privacy. The most relevant documents are those related to breast cancer.

We believe that the European Commission should implement all measures necessary to create an ad hoc directive on in vitro medical devices with predictive purposes, in order to provide greater clarity to individual Member States and uniformity of national laws on access to and use of these tests. Among the measures that the European Commission could adopt we mention the inclusion of these tests in European registries allowing better control of their use in clinical practice, and the provision of European economic measures ensuring fair access to these tests.

References

  1. COUNCIL OF EUROPE, Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine, Oviedo, 4-IV-1997.
  2. COUNCIL OF EUROPE, Additional Protocol to the Convention on Human Rights and Biomedicine, concerning Genetic Testing for Health Purposes, Strasbourg, 27-XI-2008.
  3. COUNCIL OF EUROPE, Additional Protocol to the Convention on Human Rights and Biomedicine, concerning Biomedical Research, Strasbourg, 25-I-2005.
  4. WORLD MEDICAL ASSOCIATION, Declaration of Helsinki, Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964 and amended by the: 29th WMA General Assembly, Tokyo, Japan, October 1975; 35th WMA General Assembly, Venice, Italy, October 1983; 41st WMA General Assembly, Hong Kong, September 1989; 48th WMA General Assembly, Somerset West, South Africa, October 1996; 52nd WMA General Assembly, Edinburgh, Scotland, October 2000; 53rd WMA General Assembly, Washington, DC, USA, October 2002 (Note of Clarification on paragraph 29 added); 55th WMA General Assembly, Tokyo, Japan, October 2004 (Note of Clarification on Paragraph 30 added); 59th WMA General Assembly, Seoul, Korea, October 2008.
  5. EUROPEAN PARLIAMENT AND COUNCIL, Directive 2001/20/EC of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use.
  6. UNESCO, Universal Declaration on the Human Genome and Human Rights, 11 November 1997.
  7. EUROPEAN CONVENTION FOR THE PROTECTION OF HUMAN RIGHTS AND FUNDAMENTAL FREEDOMS, Rome 4.XI.1950.
  8. EUROPEAN PARLIAMENT AND COUNCIL, Directive 95/46/EC of 24 October 1995 on the protection of individuals with regard to the processing of personal data and on the free movement of such data.
  9. COURT OF JUSTICE OF EUROPEAN UNION, Judgement 20 May 2003, Joined Case C-465/00, C-138/01, C-139/01.
  10. COMMISSION, White Paper "Together for Health: A Strategic Approach for the EU 2008-2013, COM (2007) 630.
  11. EUROPEAN COURT OF JUSTICE, Sentence of 16.05.04 (C-372/04).
  12. COMMISSION OF THE EUROPEAN COMMUNITIES, Brussels 24.06.2009, Communication From The Commission To The European Parliament, The Council, The European Economic And Social Committee And The Committee Of The Regions: An Action Against Cancer: European Partnership.
  13. EUROPEAN CODE AGAINST CANCER.
  14. EUROPEAN COMMISSION, White paper of the “Together for Health: A Strategic Approach for the EU 2008-2013”.
  15. COMMISSION TO THE COUNCIL, THE EUROPEAN PARLIAMENT, THE EUROPEAN ECONOMIC AND SOCIAL COMMITTEE AND THE COMMITTEE OF THE REGIONS E-HEALTH - Communication making healthcare better for European citizens: An action plan for a European e-Health Area.
  16. Decision of the Commission of the 23 February of 2009 that adopted the action plan for 2009 for the actualization of the second Community action plan for the health care (2008-2013)
  17. Council Recommendation on a European action in the field of rare diseases from 11.11.2008.
  18. P5_TA(2003)0270 breast cancer, the Resolution of European Parliament on breast cancer in the UE (2002/2279(INI))
  19. Recommendation no. R (89) 13 of the Committee of Ministers to Member States on the Organisation of Multidisciplinary care for cancer patients del 24.10.1989
  20. Recommendation no. r (80) 6 of the Committee of Ministers to Member States concerning cancer control del 30.4.1980
  21. Directive CEE/CEEA/CE n° 79 del 27/10/1998 98/79/EC of the European Parliament and the Council of the 27 October of 1998 concerning in vitro diagnostic medical devices
  22. Communication from the Commission Consultation regarding Community action in health services, 26.9.2006
  23. 2011/24/UE Directive of the European Parliament and the Council of 9 March 2011concerning the application of patients' rights in cross-border healthcare
  24. Recommendation Rec (2006)18 of the Committee of Ministers to member states on health services in a multicultural society from 8.11.2006
  25. Council of the European Union Directive on cross-border healthcare adopted 28.2.2011
  26. European Court calls our attention to the judgment of the Court of Justice of the European Union 28.04.1998 (C-120/95).
  27. EUNETHA, Core HTA on Genetic Tests for Breast Cancer- Draft confidential.
  28. Guidelines 2010 / C 82/01 of the European Commission on an application for a permit for a clinical trial of a medicinal product for human use
  29. COURT OF JUSTICE OF THE EUROPEAN UNION (fourth section) Sentence in Case T-179/00, A. Menarini vs. Commission of European Communities, 03.07.2002.
  30. EUROPEAN PARLIAMENT - COUNCIL OF THE EUROPEAN UNION, Directive 2001/20/CR of the from 4 April 2001 regarding the application of good clinical practices in the execution of clinical experimentation of medicines for human use
  31. EUROPEAN PARLIAMENT AND COUNCIL, Directive 2004/23/EC of the of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells.
  32. Sentence of the European Court of Justice from the 28 April of 1998 C-158/96
  33. European guidelines for quality assurance in breast cancer screening and diagnosis
  34. Commission Directive 2005/28/EC of 8 April 2005 laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use
<< Social aspectsCollection appendices >>