Towards the implementation of law n. 219/2017 on informed consent and advance directives for patients with psychiatric disorders and dementia. Physicians' knowledge, attitudes and practices in four northern Italian health care facilities.

BACKGROUND: On December 2017 the Italian Parliament approved law n. 219/2017 "Provisions for informed consent and advance directives" regarding challenging legal and bioethical issues related to healthcare decisions and end-of life choices. The law promotes the person's autonomy as a right and provides for the centrality of the individual in every scenario of health care by mean of three tools: informed consent, shared care planning and advance directives. Few years after the approval of the law, we conducted a survey among physicians working in four health care facilities specific for the care of people suffering from psychiatric disorders, cognitive disorders and dementia located in the North of Italy aiming to investigate their perceived knowledge and training need, attitudes regarding law n. 219/2017 provisions, and practices of implementation of the law. METHODS: A semi-structured questionnaire was developed on an online platform. The invitation to participate in the survey was sent by email to the potential participants. Information was collected by means of the online platform (Google Forms) which allows to export data in a spreadsheet (Windows Excel) to perform basic statistical analysis (frequency distributions, bar chart representation). RESULTS: Twenty-five out of sixty physicians participated in the survey. None of the respondents value their knowledge of the law as very good, 10 good, 13 neither poor nor good, 1 poor and 1 very poor. All the respondents want to learn more about the law (21 yes and 4 absolutely yes). The majority of respondents agrees with the content of the law as a whole (3 absolutely agree, 13 agree), and on each provision. The question on the clarity of the concept of capacity in the law received mixed answers and this impacted on the physicians' opinion regarding the legitimacy in principle for our groups of patients to realize shared care planning and write advance directives. Thirteen physicians neither introduced the theme of shared care planning nor arranged for shared care planning and the main reason for this was that no patient was in a clinical situation to require it. When shared care planning is realized, a variability in terms of type and number of meetings, mode of tracking and communication is registered. CONCLUSIONS: Our survey results indicate a need for more clarity regarding the interpretation and implementation of the law in the patient groups under study. There are in particular two related areas that deserve further discussion: (1) the question of whether these patient groups are in principle legitimized by the law to realize shared care planning or write advance directives; (2) the notion of capacity required by the law and how this notion can be declined in real-life situations.

[Capacity and right to therapeutic self-determination in law no. 219/2017. The case of persons with psychiatric and cognitive disorder.] / Capacità e diritto all'autodeterminazione terapeutica nella legge n. 219/2017. Il caso delle persone con disturbo psichiatrico e cognitivo.

Law no. 219/2017 represents Italy's most comprehensive regulatory framework aimed at enabling the exercise of the right to therapeutic self-determination and ensuring its best expression even for people without legal or natural capacity, through the tools of informed consent, shared care planning and advance care directives. Nevertheless, some criticalities affect the wording of the law, characterised by a promiscuous and heterogeneous use of the terms referring to capacity and by their interpretability. These criticalities may compromise the benefits of the law provisions at the implementation level, with particular reference to persons who may have a condition of limited capacity due to a psychiatric or cognitive disorder. We analysed the concept of capacity in the law and its critical aspects, both on a hermeneutical and applicative level. The analysis shows the difficulty of reconciling the rigidity of the legal categories of capacity with the changing and multifaceted nature of the clinical conditions. We underlined that possible correctives can come from both the healthcare contexts and legal practitioners and must be aimed at achieving maximum approximation between the formal plan of the law and the real contexts of care.

Italian law n. 219/2017 on consent and advance directives: survey among Ethics Committees on their involvement and possible role.

BACKGROUND: On December 2017 the Italian Parliament approved law n. 219/2017 "Provisions for informed consent and advance directives" regarding challenging legal and bioethical issues related to healthcare decisions and end-of-life choices. The law does not contain an explicit reference to Ethics Committees (ECs), but they could still play a role in implementing the law. METHODS: A questionnaire-based survey was performed among the ECs of the Italian Institute for Research and Care belonging to the Network of neuroscience and neurorehabilitation, with the aim of (1) knowing whether the ECs participated and, if so, how in the process of implementation of law n. 219/2017 in the referring institutes; (2) investigating the point of view of the ECs regarding their possible involvement in the process; (3) exploring the contribution ECs can provide to give effective implementation to the law principles and provisions. RESULTS: Seventeen ECs out of thirty took part in the survey; the characteristics of the responding and non-responding committees are similar, so the responding ECs can be regarded as representative of all ECs in the Network. Nine ECs did not discuss the law in anyway: the main reason for this is that the referring institutions (6) and the health care professionals (3) did not ask for an EC intervention. Nevertheless, the large majority of the ECs believe that their involvement in the implementation of the law as a whole is appropriate (8) or absolutely appropriate (6), while 3 of them are neutral. No EC believes that the involvement is inappropriate. The aspect of the law on which the 14 ECs converge in considering the EC involvement appropriate/absolutely appropriate is the one related to the health facilities obligation to guarantee the full and proper implementation of the principles of the law. CONCLUSIONS: Our survey confirms that ECs believe they can play a role in the implementation of law n. 219/2017, although this does not entirely correspond to what the committees have actually done in reality. This role could be better exercised by ECs specifically established for clinical practice, which would have a composition, functioning and a mandate better suited to the purpose. This supports the call for a national regulation of ECs for clinical practice.

Assessment of studies based on the use of questionnaires in the time of Covid-19 pandemic.

During the covid-19 pandemic a huge number of research projects have been promoted internationally, nationally and locally. This also happened in Italy which was the first affected European country. Among these studies, research protocols based on the use of online questionnaires to evaluate the reaction of health workers and researchers to the emergency situation and their state of well-being were promoted. This contribution focuses on research protocols based on the use of online questionnaires and presents as a case study three different research proposals with the purpose of showing their different degree of compliance to scientific and ethical requirements and the need for a clear regulation. A guideline for the assessment of studies based on questionnaires is then suggested, in the absence of a national regulation on the issue. Having established rules, albeit flexible, can help to guarantee transparency in the evaluation process and contribute to the scientific and ethical compliance of the research.

Conflicts of interest and Scientific Societies.

The purpose of this paper is to bring attention to the complex issue of conflicts of interest (COIs) from the point of view of Scientific Societies and their responsibility in managing secondary interests possibly undermining their activities such as improvement of professional quality, research promotion, and development of guidelines. The first publication on the issue of COIs dates back to more than a century, but only in the last decades the related ethical and legal problems have received public and professional attention. The growing role of industry in biomedical research, the significant decrease in public contributions to health, care, training, and research, and the involvement of physicians in industry-funded research have obliged to study how to identify and manage COIs. The Bioethics and Palliative Care Study Group of the Italian Neurological Society addressed the issue with a specific focus on Scientific Societies that, in our opinion, should also set an example for individual practice, raising awareness among their associates on COIs and implementing strategies for their identification and management. The paper is focused on the nature of the COI, why and how it could be managed, which policies can be implemented, and which kind of action should be considered by Scientific Societies. We emphasize the role of Scientific Societies in fostering knowledge and awareness of conflicts of interest through training and continuing education.

Advance directives as a tool to respect patients' values and preferences: discussion on the case of Alzheimer's disease.

BACKGROUND: The proposal of the new criteria for the diagnosis of Alzheimer's disease (AD) based on biomarker data is making possible a diagnosis of AD at the mild cognitive impairment (MCI) or predementia/prodromal- stage. Given the present lack of effective treatments for AD, the opportunity for the individuals to personally take relevant decisions and plan for their future before and if cognitive deterioration occurs is one the main advantages of an early diagnosis. MAIN BODY: Advance directives are largely seen as an effective tool for planning medical care in the event the subject becomes incompetent. Nevertheless, their value has been questioned with regard to people with dementia by scholars who refer to the arguments of personal identity and of patient's changing interests before and after the onset of dementia. In this paper, I discuss the value of advance directives in Alzheimer's disease and other kind of dementia. Despite critics, I argue that advance directives are especially advisable in dementia and provide reasons in favor of their promotion at an early stage of the disease as a valuable tool to respect patients' values and preferences on medical treatment, including participation in research and end of life decisions. I mainly support advance directives that include both decisions regarding health care and the appointment of an attorney in fact. CONCLUSION: I conclude that patients with AD at a prodromal or early stage should be offered the opportunity to execute an advance directive, and that not to honor a demented individual's directive would be an unacceptable form of discrimination towards those patients.

Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers.

The diagnosis of Alzheimer's disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimer's disease in research studies and specialist clinical settings. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care. We have developed a strategic five-phase roadmap to foster the clinical validation of biomarkers in Alzheimer's disease, adapted from the approach for cancer biomarkers. Sufficient evidence of analytical validity (phase 1 of a structured framework adapted from oncology) is available for all biomarkers, but their clinical validity (phases 2 and 3) and clinical utility (phases 4 and 5) are incomplete. To complete these phases, research priorities include the standardisation of the readout of these assays and thresholds for normality, the evaluation of their performance in detecting early disease, the development of diagnostic algorithms comprising combinations of biomarkers, and the development of clinical guidelines for the use of biomarkers in qualified memory clinics.

[Conscience clause in end-of-life care.] / Clausola di coscienza e cura nell'assistenza al fine vita.

The article proposes a critical reflection on issues that appeal to the conscience clause as part of end of life care can produce and what can guarantee freedom of conscience, self-determination of those involved and respect for the dignity of the sick person. After a philosophical and normative analysis, the article is organized on the basis of two important documents for discussion: a position paper of Società Italiana di Anestesia Analgesia Rianimazione e Terapia Intensiva (SIAARTI) signed by several scientific societies "Grandi insufficienze d'organo end stage: cure intensive o cure palliative?" and the Design of Law currently being debated "Norme in materia di consenso informato e di disposizioni anticipate di trattamento". In particular, the conscience clause has been discussed in the light of advance care planning (ACP), which represents the instrument to guarantee the shared planning of care and the shared-decision making. In this context, recourse to the clause of conscience brings out critical ethical and deontological issues that the article discusses, using the position paper SIAARTI and the text of law currently being debated, both built on the assumptions of a shared care relationship, where patient has a key-role in medical decisions.

Biomarkers for the diagnosis of Alzheimer's disease in clinical practice: an Italian intersocietal roadmap.

Biomarkers of brain amyloidosis and neurodegeneration/synaptic dysfunction are featured in recent diagnostic criteria for Alzheimer's disease. Several gaps in our knowledge, however, need to be filled before they can be adopted clinically. The aim of this article is to describe a roadmap, developed by a multidisciplinary task force, to rationally implement biomarkers for Italian Memory Clinics. This roadmap is based on a framework comprising 5 sequential phases: identification of leads for potentially useful biomarkers; development of clinical assays for clinical disease; evaluation of detection of early stages; definition of operating characteristics in relevant populations; and estimation of reducing disease-associated mortality, morbidity, and disability. The roadmap was devised by identifying current evidence of validity, still missing evidence, and action needed to collect this missing evidence. With appropriate adaptation to local, country-specific circumstances, the roadmap can be translated to other countries.

The biomarker-based diagnosis of Alzheimer's disease. 1-ethical and societal issues.

There is great interest in the use of biomarkers to assist in the timely identification of Alzheimer's disease (AD) in individuals with mild symptoms. However, the inclusion of AD biomarkers in clinical criteria poses socioethical challenges. The Geneva Task Force for the Roadmap of Alzheimer's Biomarkers was established to deliver a systematic strategic research agenda (aka roadmap) to promote efficient and effective validation of AD biomarkers and to foster their uptake in clinical practice. In this article, we summarize the workshop discussion of the Geneva Task Force "ethical and societal issues" working group, which comprised bioethicists, clinicians, health economists, and representatives of those affected by AD. The working group identified the following key issues that need to be included in the roadmap: improving access to services through timely diagnosis, the need for a diagnostic research protocol before moving to clinical routine, recruitment in diagnostic research protocols in the absence of effective therapy, respect for the autonomy of the individual with mild cognitive impairment in information and consent process and the right not to know biomarkers results, need for counseling programs, disclosure of the diagnosis in a structured environment and the involvement of family members, health policies including the individuals' views and the protection of their interests, and the economic costs for society.

Genetic Counseling and Testing for Alzheimer's Disease and Frontotemporal Lobar Degeneration: An Italian Consensus Protocol.

BACKGROUND: Genetic testing of familial Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) is attracting interest thanks to innovative primary prevention clinical trials and increased request for information by at-risk individuals. However, ethical, social, and psychological implications are paramount and genetic testing must be supported by structured genetic counseling. In Italy, practice parameters and guidelines for genetic counseling in dementia are not available. OBJECTIVE: To develop a nationally harmonized protocol for genetic counseling and testing of familial AD and FTLD. METHODS: Activities were carried out in the context of the Italian Dominantly Inherited Alzheimer's and Frontotemporal Network (IT-DIAfN) project, a national network of centers of excellence with expertise in managing patients with familial AD and FTLD. A survey of the literature on genetic counseling protocols and guidelines was conducted. Local protocols for genetic counseling were surveyed. Differences and commonalities among protocols were identified and discussed among project partners. Consensus was reached following implicit aggregation methods. RESULTS: Consensus was reached on a protocol for patients with clinically diagnosed familial AD or FTLD and a distinct protocol for their at-risk relatives. Genetic counseling should be provided by a multidisciplinary team including a geneticist, a neurologist/geriatrician, and a psychologist/psychiatrist, according to the following schedule: (i) initial consultation with tailored information on the genetics of the dementias; (ii) clinical, psychological, and cognitive assessment; if deemed appropriate (iii) genetic testing following a structured decision tree for gene mutation search; (iv) genetic testing result disclosure; (v) psychological support follow-up. CONCLUSION: This genetic counseling protocol provides Italian centers with a line of shared practice for dealing with the requests for genetic testing for familial AD and FTLD from patients and at-risk relatives, who may also be eligible participants for novel prevention clinical trials.

Ethical Process Reporting in Indian Dental Journals.

AIM: To study the proportion of articles reporting ethical review board (ERB) approval and informed consent process (ICP) in articles published in dental journals in India. METHODS: A descriptive study was designed, and ten Indian dental journals published by different dental specialty professional associations were selected. Among 702 retrieved articles, from 40 issues of the 10 selected journals published in 2008 and 2011, 428 meet the inclusion criteria, and they were analyzed. The entire text of the articles was manually searched for statements for ICP and ERB approval. The data was retrieved independently by two observers using an ad hoc developed template. RESULTS: 10.3% (44) of authors stated ICP, while 9.8 % (42) reported ERB approval in their articles; 6.1% (26) articles reported both the ICP and ERB. There are 21 times more chances that authors who report the ERB will also report ICP in their articles when compared to authors who report either ICP or ERB only (OR 21.3, 95% CI 8.5-52.8). Seven journals stated the ethical process reporting in the instructions for authors. Overall, 15.7% articles declared the conflicts of interests. CONCLUSIONS: The low compliance of reporting ethical protection measures in dental research among Indian dental journals is of high concern.

Research involving subjects with Alzheimer's disease in Italy: the possible role of family members.

BACKGROUND: Alzheimer's disease is a very common, progressive and still incurable disease. Future possibilities for its cure lie in the promotion of research that will increase our knowledge of the disorder's causes and lead to the discovery of effective remedies. Such research will necessarily involve individuals suffering from Alzheimer's disease. This raises the controversial issue of whether patients with Alzheimer's disease are competent to give their consent for research participation. DISCUSSION: We discuss the case of subjects with Alzheimer's disease who may have impaired decision-making capacity and who could be involved in research protocols, taking into consideration aspects of the Italian normative framework, which requires a court-appointed legal representative for patients who are not able to give consent and does not recognise the legal value of advance directives. We show that this normative framework risks preventing individuals with Alzheimer's disease from taking part in research and that a new policy that favours research while promoting respect for patients' well-being and rights needs to be implemented. SUMMARY: We believe that concerns about the difficulty of obtaining fully valid consent of patients with Alzheimer's disease should not prevent them from participating in clinical trials and benefiting from scientific progress. Therefore, we argue that the requirement for patients to have a legal representative may not be the best solution in all countries and clinical situations, and suggest promoting the role of patients' family members in the decision-making process. In addition, we outline the possible role of advance directives and ethics committees.

Public's attitudes on participation in a biobank for research: an Italian survey.

BACKGROUND: The creation of biobanks depends upon people's willingness to donate their samples for research purposes and to agree to sample storage. Moreover, biobanks are a public good that requires active participation by all interested stakeholders at every stage of development. Therefore, knowing public's attitudes towards participation in a biobank and biobank management is important and deserves investigation. METHOD: A survey was conducted among family members of patients attending the outpatient department of our institute for a geriatric or neurological visit, documenting their willingness to participate in a biobank and their views on the legal-ethical aspects of biobank management. Information regarding subjects' attitudes on biomedical research in general and genetic research in particular was also collected. Participants' data on biobanks were compared with data previously collected from the Italian ethics committees (ECs) to evaluate the extent to which lay people and ethics committees share views and concerns regarding biobanks. RESULTS: One hundred forty-five subjects took part in the survey. The willingness to give biological samples for the constitution of a biobank set up for research purposes was declared by 86% of subjects and was modulated by subjects' education. People in favour of providing biological samples for a biobank expressed a more positive view on biomedical research than did people who were not in favour; attitude towards genetic research in dementia was the strongest predictor of participation. Different from ECs that prefer specific consent (52%) and do not choose the option of broad consent (8%) for samples collection in a biobank, participants show a clear preference for broad consent (57%), followed by partially restricted consent (16%), specific consent (15%), and multi-layered consent (12%). Almost all of the subjects available to contribute to a biobank desire to receive both individual research results and research results of general value, while around fifty per cent of ECs require results communication. CONCLUSION: Family members showed willingness to participate in a biobank for research and expressed a view on the ethical aspects of a biobank management that differ on several issues from the Italian ECs' opinion. Laypersons' views should be taken into account in developing biobank regulations.

Biomarker-based diagnosis of mild cognitive impairment due to Alzheimer's disease: how and what to tell. A kickstart to an ethical discussion.

New criteria for the diagnosis of Alzheimer's disease (AD) based on biomarker results have recently been developed and are currently undergoing extensive validation. The next few years may represent a time window where the diagnostic validity of biomarkers will be studied in highly specialized research settings. Biomarkers results will be used to direct clinical diagnosis and, whenever appropriate, therapy and management. This piece aims to stimulate discussion by identifying the ethical challenges involved in the use of biomarkers to make a diagnosis of mild cognitive impairment due to AD and disclose it to patients. At the individual level, these challenges are related to (i) the ethical appropriateness of implementing an ecological diagnostic research protocol, (ii) the related informed consent process, and (iii) the diagnostic disclosure. We justify the ethical legitimacy of implementing a research diagnostic protocol by referring to the respect of patients' subjectivity and autonomy, and we suggest guidelines for informed consent development and diagnostic disclosure. All of the above points are discussed in light of the unique features of AD, currently scanty treatment options, and knowledge and uncertainties regarding the diagnostic value of biomarkers.

Participation in biobanks for research by incapacitated adults: review and discussion of current guidelines.

OBJECTIVE: Biobanks for research and genetic research are important opportunities to create new understanding of complex disorders, such as psychiatric disorders and dementia. The management of biobanks for subjects with psychiatric disorders or dementia raises additional challenges because of the ethical issues regarding the potentially impaired decision-making capacities of the subjects. The aim of this paper is to study (i) how guidelines address the matter and (ii) how they can be implemented in real research situations with patients suffering from psychiatric disorders and dementia. METHOD: We collected and analysed all the relevant guidelines and position papers from national and international organizations dealing with research on biological materials and selected documents mentioning the participation of incapacitated adults in genetic research and biobanks. RESULTS: Eighteen of the 30 analysed documents contain explicit references to adults who are unable to give consent. The main topics addressed by the guidelines are the following: (i) informed consent; (ii) principles of non-therapeutic research; and (iii) ethics committee review. CONCLUSIONS: In biomedical research, guidelines are an important instrument for facilitating research while promoting subjects' rights and well-being. Compared with legally binding documents, guidelines are more flexible and can be more easily revised according to evolving research situations and for adaptation to real persons and research settings. We suggest measures to implement the analysed guidelines taking into consideration the case for the participation of patients with neuropsychiatric disorders, who can have impairment of decision-making capacities without being obviously incompetent, in genetic research and biobanks.

The policies of ethics committees in the management of biobanks used for research: an Italian survey.

Gaps in regulations pertaining to the collection and storage of biological materials in a biobank, at least in the European context, have made the writing of local guidelines essential from an ethical point of view. Nevertheless, until recently, the elaboration of local guidelines for the collection, use and storage of biological materials in a biobank has been the exception in Italy and all European countries. In this context, it is of value to know the policies, even if they are unwritten, of local ethics committees (ECs) engaged in the evaluation of research protocols involving biobanks and biological materials. This paper presents the results of a survey carried out among local Italian ECs (229) to document their attitudes and policies regarding the management of the ethical issues related to biobanks and the use of biological materials. A questionnaire was developed to investigate the areas regarded as critical from an ethical-legal point of view: informed consent and information to the subjects; protection of confidentiality; communication of research results; access/transfer of biological materials and related data; ownership of samples and data and intellectual property rights; and subjects' remuneration and benefit sharing. Twenty-six ECs from the Italian Institutes for Research and Care (62%) and 26 other ECs (14%) participated in the survey.