Common to all used applications

Use the target condition and International Classification of Diseases (ICD) codes defined in the scope of the project and consider adding details such as: description of anatomical site, disease aetiology and pathophysiology, types of disease or classification according to origin, subtype, severity, stages, or risk level and different manifestations of the condition. The following properties of the target condition are defined in separate assessment elements: risk factors (A0003), natural course (A0004), symptoms (A0005) and burden of disease for the society (A0006).

Common to all used applications

Describing risk factors is especially important when they suggest possibilities for primary and secondary prevention. This information may affect the choice of comparator or the appraisal of the overall value of the technology under assessment. The risk factors for acquiring the condition, and the risk factors for relapses or worsening of the condition should be reported here separately. The prevalence of the various risk factors might differ in different geographic areas and among different subpopulations.

Common to all used applications

This assessment element should provide information on the prognosis and course of the health condition when untreated. This information is relevant for appraising the overall value of the technology. It may also guide the assessment of the predicted value or effectiveness of the technology, as technologies may work differently at different stages or severity grades of the disease, and there may be a relationship between earlier intervention and better prognosis. This element should also provide information on the time lag between the onset of disease and the symptoms or other findings that eventually trigger the need of diagnostics and care.

Common to all used applications

This element should describe the patients’ relevant symptoms before intervention with the technology, their severity and whether they are persistent, intermittent or undulating taking into account different stages of the disease. Patients’ perceptions of the burden of the disease are not always in line with the clinical seriousness of the disease or its societal burden.

Common to all used applications

Describe consequences and burden of the disease or health condition by providing information on prevalence or incidence of the disease that is prevented or treated by using the technology; disease-specific mortality and disability, life years lost, and/or disability-adjusted life years, QoL, quality-adjusted life years (QALYs).

Common to all used applications

There are both international and national market authorisation systems. The systems differ between countries and are more established for pharmaceuticals than for medical devices. An overview of the status with regard to key processes, e.g. CE marking, EMA/US Food and Drug Administration (FDA) approval is recommended. In case the technology is authorised under a different process, e.g. adaptive licensing or conditional reimbursement, information should be presented. Also, information on national data and an analysis of possible discrepancies can be useful.

Specific to diagnostic technologies:

Imaging devices may require approval. Substances needed for obtaining images may require additional approval (e.g. radiotracers). In some cases, the approval for primary screening is different to that for clinical use (FDA recently licensed tests explicitly for screening), but in most cases, approval is obtained for diagnostic use and the test is proposed for screening without any other formal approval.

Specific to screening technologies:

Imaging devices may require approval. Substances needed for obtaining images may require additional approval (e.g. radiotracers). In some cases the approval for primary screening is different to that for clinical use (FDA recently licensed tests explicitly for screening), but in most cases approval is obtained for diagnostic use and the test is proposed for screening without any other formal approval.

Common to all used applications

Information on national reimbursement status from different countries for the technology as well as the comparators, including key dates and anticipated licensing time frame. Information on full coverage, co-payments and coverage under special circumstances/conditional coverage is useful.

Common to all used applications

The effectiveness of an intervention may vary in populations which are diagnosed by different diagnostic pathways. A sensitive test tends to have low specificity such that there are several people who do not have the condition among the test-positive population. The effectiveness of an intervention in that population may be lower than in a population examined with a less sensitive test (but with more true-positive cases). It is important to point out possible discrepancies between guidelines and actual practice.

Common to all used applications

It is important to describe whether the technology is an add-on or a replacement for the existing management options, and what the other evidence-based alternatives are. Are there differences in the treatment of diseases at different disease stages? Deviation from evidence-based guidelines may suggest over- or under-use of the technology. Identification of practice variations due to the differences in the forms, stages or severity of the disease may imply differences in the quality of health care. Different stages of disease may call for different therapeutic procedures (e.g. aortic insufficiency is first treated with medication, and at a certain point of cardiac structural changes, an operation is preferred). Provide an overview of other treatment alternatives. Likewise, diagnostic or monitoring methods used for various diseases may vary depending on the stage of disease.

Common to all used applications

Relevant for all assessments: both safety and effectiveness depend largely on the subpopulation towards which the intervention is targeted. The technology may be used for all patients with the condition, or only those in the early stages, or at a specific severity level or for those at moderate risk of having the condition. Personalised medicine divides the target population into even smaller units when targeting the intervention to specific subgroups based on e.g. genetic profile. Use the target population defined in the scope of the project, and consider adding further details and description of who defined the selected subgroups and why. Point out e.g. if certain populations should be excluded from the analysis. 

Common to all used applications

This information can be used to give an idea of the resource requirements in general for implementing the technology. Estimates of incidence and prevalence should be provided. Estimates of likely relevant increases or decreases in the size of the target population in the future should also be included.

Common to all used applications

Provide national estimates for current and future utilisation rates for the indication under assessment, for both the technology under assessment and its comparators. Variations in utilisation reflect market access, sales figures, actual usage in hospital level and adherence to the use of the technology by professionals and patients. Data on current and previous utilisation reflect the phase of the technology (experimental, emerging, established or obsolete). This also has implications for the availability of evidence and the level of uncertainties.

Specific to screening technologies :

What is the current rate of screening adherence?

Common to all used applications

This is relevant in all assessments. Use the descriptions of the technology and comparator(s) defined in that scope and elaborate them here in more detail.

Technology may include a single device, a questionnaire, imaging or sequence of technologies. The HTA may address one or several similar technologies. Describe separately for the technology and the comparator: the type of device, technique, procedure or therapy, its biological rationale and mechanism of action; and also, describe how the technology differs from its predecessors, and the various current modifications or different sponsor’s products, especially if the differences affect performance.

Common to all used applications

There are both international and national market authorisation systems. The systems differ between countries and are more established for pharmaceuticals than for medical devices. An overview of the status with regard to key processes, e.g. CE marking, EMA/US Food and Drug Administration (FDA) approval is recommended. In case the technology is authorised under a different process, e.g. adaptive licensing or conditional reimbursement, information should be presented. Also, information on national data and an analysis of possible discrepancies can be useful.

Specific to diagnostic technologies:

Imaging devices may require approval. Substances needed for obtaining images may require additional approval (e.g. radiotracers). In some cases, the approval for primary screening is different to that for clinical use (FDA recently licensed tests explicitly for screening), but in most cases, approval is obtained for diagnostic use and the test is proposed for screening without any other formal approval.

Specific to screening technologies:

Imaging devices may require approval. Substances needed for obtaining images may require additional approval (e.g. radiotracers). In some cases the approval for primary screening is different to that for clinical use (FDA recently licensed tests explicitly for screening), but in most cases approval is obtained for diagnostic use and the test is proposed for screening without any other formal approval.

Common to all used applications

This issue is especially relevant in new technologies with uncertain expectations and claims of benefit.

Describe the following aspects:

• How is it expected to be an improvement over previous/existing technologies used for the same health problem?
• The expressed objectives for the implementation of the technology in health care; what are the claimed objectives (e.g. increased safety, health benefit, accuracy or patient compliance), and is it intended to replace or to supplement existing technologies?

Common to all used applications

Most technologies will be introduced at approximately the same time in several countries. This information is relevant for the assessment while the evidence base may change rapidly for technologies that are at an earlier stage in their development. It is also important to establish whether new versions of the technology with substantial improvements are expected in the near future. For end-users it is useful to know whether new versions or adaptations of the technology are expected in the near future.

Describe the following aspects:

• Is the technology an innovation?
• When was it developed?
• Is the technology only partially innovative (i.e. a modification of an existing technology), and in that case, is it possible to specify the degree of innovation the technology may represent?
• When was the technology introduced into health care?
• Is the technology an already established one, but now used in a different way, for instance for a new indication? This issue may be less relevant for new pharmaceuticals.
• Is it experimental, emerging, established in use or obsolete (implementation level)?
• Is the technology field changing rapidly?
• How does this technology differ from its predecessors (other technologies used for similar purposes)?
• Are there new aspects that may need to be considered when applying it?
• Is there evidence that the technology works (or is used) outside its current indication area or produces incidental findings that can have consequences relevant to effectiveness, safety, organisational, social and ethical domains?

Common to all used applications

This issue should be answered in case there is a relevant difference between the technology and the comparator. Describe the following aspects:

• Which professionals (nurses, doctors, and other health-care professionals) apply and make decisions about starting or stopping the use of the technology?
• Do the patients themselves, or their carers, administer the technology?
• Who can select the patients, make referrals, decide to initiate the use of the technology or interpret the outcome?
• Are there certain criteria (skills, function, training requirements) for the patients or professionals who will administer the technology?

Describe the level of care in which the technology is used: self-care, primary care, secondary and tertiary care. If secondary or tertiary care, describe whether it is intended to be used in the outpatient or inpatient setting.

Its role in the management pathway can be presented as a replacement, an add-on or for triage.

Common to all used applications

This issue should be answered in case there is a relevant difference between the technology and the comparator.

Many technologies require purpose-built premises, such as radiation-secured areas, Faraday cages, dressing rooms for the patient, or specific premises equipped with fume cupboards for storage and reconstitution of chemotherapy pharmaceuticals. Typical premises in primary or secondary care may differ markedly from country to country. A clear description of necessary facilities is needed instead of a general statement (e.g. to be used in hospitals only).

This issue may be less relevant for pharmaceuticals.

Common to all used applications

This issue should be answered in case there is a relevant difference between the technology and the comparator.

Examples are syringes, needles, pharmaceuticals and contrast agents, fluids, bandages and tests to identify patients eligible for treatment.

Common to all used applications

Information on national reimbursement status from different countries for the technology as well as the comparators, including key dates and anticipated licensing time frame. Information on full coverage, co-payments and coverage under special circumstances/conditional coverage is useful.

Common to all used applications

Here, one should identify and describe the direct harms of the use and the administration of the technology and the comparator(s). Highlight the differences in the most important risks (i.e. the most severe and frequent harms) of the technology and its comparator and consider if there are uncertainties with regard to safety because of small numbers and/or short duration of follow-up.

Consider:

• What is the frequency and what are serious adverse events (SAEs) of the technology in relation to the comparator(s)?
• What are the most frequent AEs of the technology in relation to the comparator(s)?
• What is the frequency of discontinuation of treatment due to AEs of the technology in relation to the comparator(s)?
• What is the frequency of SAEs leading to death for the technology in relation to the comparator(s)?
• What is the frequency of unexpected AEs in participants and comparison groups?     

Common to all used applications

This is usually relevant with pharmaceuticals but may also be relevant with medical devices and procedures. Before marketing authorisation, it is relevant to report harms at any dose. After market access, the harms at doses normally used in practice are most relevant for HTAs. Information should be included if safe use of the technology is sensitive to even small changes of the dose because this may have implications for the training and organisation of care. The potential for accumulated harm due to repeated dosage or testing should also be considered.

Specific to pharmaceuticals:

For further information, see guideline on Endpoints used for REA  – Safety.

Common to all used applications

This issue is especially relevant for new or evolving technologies where there are considerable uncertainties in the safety evidence, and in technologies with steep learning curves. How does the safety profile of the technology vary between different generations, approved versions or products? Is there evidence that harms increase or decrease in different organisational settings?

Common to all used applications

Typically, people with comorbidities and co-medication, pregnancy, intolerances, specific genetic profiles, elderly people, children and immunosuppressed patients. Are there any relevant contraindications or interactions with other technologies?

Common to all used applications

Describe here what is known of the harms caused by the properties or behaviour of professionals, patients or other individuals who apply or maintain the technology. Is there e.g. a noteworthy risk of malfunction of a device, due to deficient user training or personal attitude; or a risk of errors related to reconstitution, dosage, administration or storage of medicines, that may have serious consequences; or, is there a risk of addiction? Describe what is known of the learning curve, intra- or inter-observer variation in interpretation of outcomes, errors or other user-dependent concerns in the quality of care. For further information, see guideline on Endpoint used for REA  – Safety.

Common to all used applications

Describe the data that needs to be collected about the care process, professionals involved, patients and their health outcomes. These include clinical indications, specified populations, prescriber information, inpatient or outpatient use, test results, review period and health outcomes. In case of new technologies, consult the EVIDENT database.

Specific to pharmaceuticals: refer to the SPC and EPAR.

Describe the general importance of having a registry to monitor the use of this particular technology and the comparator. Are there existing registries that should be used, or should a registry be established, to collect the necessary data to monitor safety or true life effectiveness? Provide national examples. Sometimes registries are connected with the risk-sharing scheme that innovative pharmaceuticals require in some countries. Notice also the requirements of pharmacovigilance monitoring.

Common to all used applications

What are the consequences of false-positive, false-negative and incidental findings generated by using the technology?

False-negative test results (Type II error) identify sick people incorrectly as healthy with the possible consequence of incorrectly rejected or delayed treatment. The volume of false-negative test results can be estimated to be 1-sensitivity of the test.

False-positive test results (Type I error) identify healthy people incorrectly as sick with the possible consequence of over-treatment. The volume of false-positive test results can be estimated to be 1-specificity of the test. Incidental findings in tests carry major risk of over-diagnosis and over-treatment.

Specific to screening technologies :

In screening programmes, one should consider separately the false-negative screening test results and the subsequent false-negative diagnostic test results.

Common to all used applications

Report the results both in absolute terms and relative to the comparator. Mortality is the preferred, objective endpoint for assessments of life-threatening conditions. Overall mortality, disease-specific mortality and mortality due to causes other than the target disease are distinguished. Several methods are used to adjust mortality rates and survival curves, e.g. relative survival (observed versus expected survival), which can be quite misleading; and HR (derived from a statistical method comparing the median survivals in the two groups). Note that progression-free survival is not a mortality endpoint; it describes the time from the beginning of an intervention until a patient shows signs of disease progression.

Overall mortality refers to all-cause mortality. It is expressed either as mortality rates (incidence in given population, at given time point and usually risk standardised), or survival (number of people alive for a given period after an intervention).

Disease-specific mortality is a proportion of all-cause mortality. It should be noted that even if a given treatment reduces one type of death, it could increase the risk of dying from another cause, to an equal or greater extent. Disease-specific mortality is typically presented as rates and as age- and risk-adjusted measures such as HR. It is a frequently used endpoint in screening trials, where it is considered to be subject to bias. Consider separately, absolute mortality (compared with placebo or waiting list) and mortality relative to the comparator.

Mortality due to causes other than the target disease includes all unintended, either positive or negative effects of the technology on mortality. There may be e.g. a decrease of mortality of another disease observed or suspected; or increased mortality due to accidents or hazardous medical interventions after false-positive or incidental test results. Supplement with relevant data if differences can be expected for specific subgroups.

Disease-specific mortality is a proportion of the all-cause mortality. It should be noted that even if a given treatment reduces one type of death, it could increase the risk of dying from another cause, to an equal or greater extent. Disease-specific mortality is typically presented as rates and as age- and risk- adjusted measures such as HR. It is a frequently used endpoint in screening trials, where it is considered to be subject to bias. Supplement with relevant data if differences can be expected for specific subgroups.

Specific to diagnostic technologies:

In diagnostic and screening technologies, this issue refers to the expected beneficial effect of the test-treatment chain.

Specific to screening technologies:

In diagnostic and screening technologies, this issue refers to the expected beneficial effect of the test-treatment chain. With screening tests, one should consider the effects of lead-time bias, length-time bias and selection bias to the mortality.

Common to all used applications

Report the results both in absolute terms and relative to the comparator. Describe the efficacy and effectiveness of the technology on relevant disease outcomes (symptoms and findings). Outcomes such as function, QoL and patient satisfaction are reported in other assessment elements of this domain. Report changes in severity, frequency and recurrence of symptoms and findings.

Supplement with relevant data if differences can be expected for specific subgroups. (see guideline on Endpoints used for REA  – Clinical endpoints).

Common to all used applications

Report the results both in absolute terms and relative to the comparator. Report here efficacy and effectiveness outcomes such as complete cure, progression-free survival, time-to-event, next stage of disease, relapse. Describe here the duration of treatment effect on symptoms and findings: permanent, short-term, long-term, intermittent, undulating.

Supplement with relevant data if differences can be expected for specific subgroups.

Common to all used applications

Report the results both in absolute terms and relative to the comparator. International classification of function proposes the following categories for body functions: mental, sensory and pain, voice and speech, cardiac, respiratory and immune functions, genitourinary and reproductive functions, movement-related, and skin functions. Report the results both in absolute terms and relative to the comparator. Supplement with relevant data if differences can be expected for specific subgroups.

Common to all used applications

Report the results both in absolute terms and relative to the comparator. Supplement with relevant data if differences can be expected for specific subgroups. Activities of Daily Living (ADL) is used in rehabilitation as an umbrella term relating to self-care, comprising those activities or tasks that people undertake routinely in their everyday life. The activities can be subdivided into personal care and domestic and community activities.

Common to all used applications

Report the results both in absolute terms and relative to the comparator. Supplement with relevant data if differences can be expected for specific subgroups.

Health related quality of life (HRQoL) is typically measured with self- or interviewer-administered questionnaires to measure cross-sectional differences in QoL between patients at a point in time (discriminative instruments) or longitudinal changes in HRQoL within patients during a period of time (evaluative instruments). Two basic approaches to HRQoL measurement are available: generic instruments that provide a summary of HRQoL; and specific instruments that focus on problems associated with single disease states, patient groups, or areas of function. Generic instruments include health profiles and instruments that generate health utilities. Each approach has its strengths and weaknesses and may be suitable for different circumstances.

Common to all used applications

Report the results both in absolute terms and relative to the comparator. Supplement with relevant data if differences can be expected for specific subgroups. HRQoL is typically measured with self- or interviewer-administered questionnaires to measure cross-sectional differences in QoL between patients at a point in time (discriminative instruments) or longitudinal changes in HRQoL within patients during a period of time (evaluative instruments). Two basic approaches to HRQoL measurement are available: generic instruments that provide a summary of HRQoL; and specific instruments that focus on problems associated with single disease states, patient groups, or areas of function. Generic instruments include health profiles and instruments that generate health utilities. Each approach has its strengths and weaknesses and may be suitable for different circumstances.

Common to all used applications

Describe patients’ overall perception of the value of the intervention and their satisfaction with the treatment. For further information, see guideline on Endpoints used for REA – Clinical endpoints.

Common to all used applications

A more accurate replacement test could improve treatment and effectiveness. A satisfactory triage test may decrease the number of adverse outcomes from another test. An add-on test may increase sensitivity so that more patients receive proper treatment and thus improved outcomes.

Common to all used applications

Accuracy in terms of sensitivity and specificity, and other measures such as likelihood ratios, pre-test probabilities, SDORs, area under the curve (AUC) or Q.

Common to all used applications

Sensitivity and specificity vary according to the threshold value. Optimal combination of sensitivity and specificity defines optimal threshold value. The optimum depends on the consequences of the test results, e.g. whether it does more harm to overlook a case or to treat someone unnecessarily.

Specific to screening technologies:

In screening programmes, one should consider separately the screening test and the subsequent diagnostic tests.

Common to all used applications

Decisions concerning the implementation of new technologies generally require carefully considering the balance between benefits and harms. Examples of questions that can be answered are:

Who is the right candidate for the technology? What is the balance between benefits and harms? For instance, is the technology estimated to improve health, health-related quality of life, quality of life and/or survival compared to alternative technologies? Can the technology harm individual patients, or any other stakeholder, in any way? How many patients might face harm in order for the technology to have a benefit for one patient? What is the extent of these benefits and harms?

What are the perceived benefits and harms of the technology in the eyes of the patients/users themselves? It might be useful to note that the patient is often the best judge of benefits and harms for themselves.

Common to all used applications

Examine the following: Can the technology have positive effects for others apart from the patients in question? Can the technology harm relatives, other patient groups, organisations, commercial entities, society, etc.? Some technologies have the potential to unfold unwanted or harmful effects not only on the patients that the technology is directly applied to but also indirectly on others. For example results of genetic tests may negatively interfere with the family planning and social life of not only the individual being tested but also of his or her relatives. Another example is how the caregivers’ burden and well-being will be affected by the technology.

Benefits and harms to individuals must be balanced with benefits and harms that can have impact on society as a whole (social utility, maximizing public health). These harmful effects may manifest themselves in the physical, social, financial or even other domains of life.

Changes in the availability of new, more effective technologies may significantly alter the requirements placed on the health care system. Is the symbolic value of the technology of any moral relevance?

Another relevant question is how the assessed technology relates to more general challenges of modern medicine (over-diagnosis, medicalization)?

Table 1 in the process description can be used to describe benefits and harms.

Common to all used applications

The technology may be used for other indications (extended use) or other purposes, e.g., in combination with other technologies (unintended use). It may have side-effects in addition to those following from the intended use.

Consider not only the consequences of the formal intended use of the technology, but also the ethical consequences of unintended and extended use. If unintended consequences are not well-known, they should be speculated and elaborated upon. Evaluate the intended purpose and uses of the technology against the likely uses and consequences of the technology in reality.

The mode of delivery, the need for laboratory tests or clinical follow-up to ensure safe and effective dosage and the way of delivery (at home, outpatient or in-patient) may have a large impact on the health care processes, systems and on individuals. They may also change the concepts of disease and normality (e.g. change an untreatable cancer into a chronic disorder or changing the border values when the concept of normality also changes).

New technologies tend to lead to new areas of inventions and give rise to new ethical questions (e.g., in vitro fertilisation (IVF) and development of genetic testing has led to questions of preimplantation genetic diagnostics (PGD)). As pre-symptomatic screening tests have become available, the healthcare system has to be prepared to handle moral issues raised by true positive and false negative findings.

Another relevant question is whether or not there will be a moral obligation related to the implementation, withdrawal, or use of the technology (e.g. check-ups or alternative procedures).

Specific to Diagnostic Technologies

Diagnostic technologies may also have effects on relatives. Not only genetic tests, but all diagnoses of hereditary disorders, also provide knowledge about relatives. Diagnostic information may also affect social relations (e.g. STD)’.

Specific to Pharmaceuticals

Pharmaceuticals have usually been designed and studied for a specific and defined group of patients, but they may be used for a larger group (variation in age and severity of the disorder and persons with comorbidities and/or need for other pharmaceuticals). Expensive pharmaceuticals (orphan disorders, new cancer treatments) and the prescription of pharmaceuticals according to genetic profiles challenge the equal and just use of health care resources. The health care system has to be prepared to handle moral issues raised by the new, expensive possibilities to treat rare, otherwise non-treatable disorders and to prolong life in chronic disorders.

Specific to Screening Technologies

Screening positive and being diagnosed with the disease may have effects on relatives as all diagnoses of hereditary disorders also provide knowledge about relatives. Screening results may also affect social relations.

Common to all used applications

When assessing benefits and harms of an intervention there may be ethical obstacles to the conduct of further research in order to strengthen the scientific basis. This concerns issues like the following:

• When clinical experience shows that the intervention has an effect on a group for whom there are no treatment alternatives and it would thus be ethically unacceptable to conduct a study in which the comparative group would be denied the procedure,

• In the case of a vulnerable group of subjects who are difficult to study,

• Where specific integrity problems would arise if research were to be conducted.

Common to all used applications

Clarify the right and justification to use the technology on vulnerable persons. Persons who are vulnerable could, for example, be pregnant women (in which case their unborn child needs to be protected), critically ill patients or individuals that have reduced decision-making capacity (children, persons with cognitive disabilities or patients that due to their illness/state have limited decision making capacity). Who has the right to balance the benefit against possible harm in these situations? On what grounds can these decisions be made? Is the technology so valuable, as to justify its use on people who cannot give informed consent?

Common to all used applications

Many technologies can alter a person´s self-determination. The technology may interfere with a patient’s right to autonomy, directly or indirectly, by influencing/subtracting their decisional capacity. However, patients have, in most cases, a right to autonomy, i.e. a right to be self-governing agents. This means they possess both the right to decide (not) to use/participate, and the right to receive relevant information. Drugs for sedation and surgical treatment of severely ill patients are examples where patient autonomy may be reduced.

Technology may require users/patients to behave in a certain way (e.g. dietary restrictions for faecal blood test). In order to be able to decide autonomously, the user/receiver of the technology should understand all alternative treatments or different therapeutic paths following test results. They should be able to make informed consent at every step.

The practical challenge with treatment technologies is that, in order to be fully autonomous, the patient should understand not just direct risks of the treatment, but also all alternatives, whether side-effects take place, and how these can affect the living quality or choices (e.g. car driving, nutrition).

Common to all used applications

Focus on the following: Is the common professional practice of discussing the technology with patients enough, or is special information needed to decide on this technology? Can the technology entail special challenges/risks that the patient/person needs to be informed of? Should the patient be explicitly informed, for example, that false positive results of a test may lead to unnecessary further investigations and treatments, sometimes with serious harms? An example is screening programmes for early identification of life-threatening situations that may have life-threatening side effects, such as invasive surgery with risk of death. Technology used for off-label use may have unexpected severe side-effects (e.g. patients with comorbidities or children).

The information should enable the user/receiver of the technology to understand the technology and its associated risks/challenges. It should be in accordance to their personal values and intellectual capacity, thereby enabling users to decide accordingly. The patient should be explicitly informed, for example, that the treatment may have serious side effects, may have an effect on personality or lead to increased need of sleep or serious weight gain. They should also be informed of when the mode of delivery or action may affect their daily life (e.g. no car driving allowed, restricted travelling).

Common to all used applications

Technologies may change the patient-physician relationship, challenge professional autonomy or otherwise interfere with professional ethics and values. The patient-physician relationship is traditionally based on mutual trust, confidentiality and professional autonomy so that individual treatment decisions can be made in the best interest of the patient. Technologies that interfere with core values and principles of medical and professional ethics challenge the professional integrity of the physicians or other healthcare professionals (e.g. screening for drug abuse when use is denied). Technologies that are aligned with professional ethics are more likely to be implemented successfully. For example, people may ask for the technology for many reasons, while the professionals may see them as unnecessary and even potentially harmful (e.g. antibiotics, sleep medicine, antidepressants, whole body MRI scans).

Common to all used applications

Especially those technologies that are applied to persons with reduced autonomy (children, mentally impaired, severely ill) may violate a person's dignity, i.e. challenge the idea that all human beings have intrinsic value, and should thus not be seen as means to others ends. Labelling people as result of using the technology may also threaten their dignity.

Some technologies may cause healthy people to be labelled as sick (e.g. PSA for prostate cancer) or otherwise less worthy, abnormal, less clean, etc. For instance labelling people as needing psychiatric medication for their behavioural difficulties may threaten their dignity. People with physical disabilities may be labelled by prenatal screening programmes, which imply that their handicap is an indication for abortion.

Common to all used applications

A technology may challenge integrity by preventing (or having the possibility to prevent) patients to live according to their moral convictions, values, preferences or commitments. It may also interfere with the coherent image or identity of the user’s self. This is especially important to analyse for vulnerable patient groups.

The technology may challenge religious, cultural or moral convictions or beliefs of some groups (e.g. pharmaceuticals produced from human blood given to cultural groups that do not accept blood transfusion, pharmaceuticals used for abortion in cultural groups that do not accept abortion, and assisted reproductive technologies that have separated the concept of genetic, biological and social motherhood).

The technology may change generally or locally accepted social arrangements by challenging traditional conceptions or social roles. For instance, ADHD medication might challenge the integrity of people who value personality, and cochlear implants may be problematic for those who do not see deafness as a disability.

Identifying the conceptions behind the beliefs and values may help put them in perspective when considering the ethical consequences of use and the overall acceptability of the technology. When possible, considering other acceptable alternatives for the affected groups of users is important. Use of the technology can also be detrimental to integrity if it is associated with discouraging honesty or ethical conduct, e.g., systems that encourages users to lie about their health state in order to get better service/treatment.

Common to all used applications

The sphere of privacy can be invaded both virtually and physically. Describe, e.g., these issues: Does the technology affect the population’s possibility to have control over personal information? Is dissemination or gathering of information regarding the individual patient or the population justified? Is cooperation and sharing of information with professional groups outside the health services needed? Is the handling of personal information reasonable, given the purpose of using the technology? Is the technology more or less invasive than the alternatives, regarding the physical body and/or the spatial sphere? Is a violation of the privacy of the patient or population necessary and reasonable to achieve desired outcomes?

Common to all used applications

Many technologies imply substantial costs, sometimes covered with resources from other areas. A new technology may require re-allocation of human resources, funding and training. A large re-allocation of resources may seriously jeopardise other patient groups (e.g. new technology that requires human resources in acute care or new diagnostic technology that uncovers a large pool of unmet needs for treatment). How this reallocation affects the existing health care system has to be studied. Who will gain and who will lose? Is the prioritisation explicit or implicit?

Specific to Diagnostic Technologies

Diagnostic technologies sometimes acquire significant symbolic value (e.g. foetal ultrasound, PSA) that may create demands for tests that are not justified on health grounds.

Specific to Pharmaceuticals

Pharmaceuticals may acquire abstract promise of health benefit that may create demand that is not justified. Some diagnosis may create demands for pharmaceuticals that are not always justified to be prescribed on health grounds (e.g. large variation in prescribing ADHD medication for children by various countries).

Specific to Screening Technologies

Screening technologies sometimes acquire significant symbolic value (e.g. foetal ultrasound, PSA) that may create demands for tests that are not justified on health grounds.

Common to all used applications

Clearly presenting how technologies with similar ethical issues are treated in a healthcare system may help in adopting coherent and just health policies, either by applying past precedents to current cases, or by showing that past cases need reconsideration. Similarity is to be defined individually for each technology. The idea is to focus only on the similarities relevant for solving the ethical problems considered important for the current HTA project. The similar ethical problems can be related to similarities in the technology’s medical, technological, economic, social, organisational or legal nature.

Common to all used applications

This issue concerns inequality in health. Investing in the reduction of health inequalities is a target of the European Commission, as it contributes to social cohesion and breaks the vicious spiral of poor health being a contributor to, and a result of, poverty and exclusion. Can the technology be applied in a way that gives equal access to those in equal need? How can this be guaranteed? Could potential discrimination or other inequalities (geographic, gender, ethnic, religious, employment, insurance) prevent access?

Common to all used applications

The basic human rights are most notably declared in the United Nations Declaration of Human Rights (http://www.un.org/en/documents/udhr/ ). They are universal and consider the most important goods, protections and freedoms for mankind. For HTA, perhaps the most relevant are the rights to equality, non-discrimination, safety, adequate standard of living, and healthcare.

Common to all used applications

Describe whether legislation and regulation to use the technology is fair and adequate. Use of the technology may lead to ethical issues that make current regulations inadequate. Screening and diagnostic technologies are commonly regulated differently than treatments, especially medications. Ethical reflection is essential in order to assess what kind of legislation, regulation or amendments are needed.

Common to all used applications

Address any risks of the chosen end-points, cut-off values or comparators/controls giving a biased description of the results of the technology.

Clinical effectiveness should ideally be directly related to the disease under treatment. This is not always entirely possible, so other end-points may need to be used (e.g. surrogate markers for preventing a life-threatening disease). In addition, the technology may have several aims (e.g. those related to treating the disease and preventing secondary morbidity).

The choice of cut-off values for sensitivity and specificity should be done considering the moral value of different results – for example, high specificity is required if false positives have serious consequences.

Common to all used applications

Consider whether there are any ethical problems related to the data or assumptions that have been used in the economic evaluation. An example is whether or not indirect costs have been valued in a fair and adequate way.

Common to all used applications

At what time of the technology’s lifetime is the technology assessed? What are the consequences of assessing the technology with respect to prioritisation?

Who would (not) get access to the new technology, as result of conducting HTA at this point of time? If there are methodological and ethical obstacles to fill a knowledge gap, what are the consequences for the patient group if the knowledge gap cannot be filled in the (near) future? Should the technology be made available to patients despite the inadequate scientific basis at the time of assessment?

Common to all used applications

Describe current tasks and work processes. This helps illustrate the whole process as well as the continuity of care across professional and organisational boundaries. Who is doing what in the process?

There are many actors at different levels (intra-organisational, inter-organisational and health care system level) in the process. Continuity should be ensured so that there will be no gaps between the steps of the process.

Explain what kind of changes a new technology could have: it might replace or reduce some activities. In addition, the new technology may have an impact on current pathways of care (e.g. shift towards community care or inpatient care).

Specific to Diagnostic Technologies

The implementation of a new diagnostic test can substantially increase (or decrease) the number of patients in need of treatment thus changing the relationships between different organizations and influencing the health care system as a whole.

Specific to Pharmaceuticals 

Specify the differences in work processes between the new medicine and the comparator. For example, the new medicine does not need routine laboratory unlike the comparator.

Specific to Screening Technologies

Describe how the screening process has been organised, e.g. (1) how the target population is chosen; (2) how and by whom the invitation is carried out (open/fixed invitation, announcement/personal invitation letter); (3) how and by whom the information for consent is given; (4) how, where and by whom the test is executed, 5) how, where and by whom the further investigations and treatment are carried out; (6) how, when, and by whom the follow up services are carried out (e.g. notification of results, recalls, reminders).

It’s important to describe all steps needed in the screening process for the economic evaluation.

Common to all used applications

This issue deals with the path of the patient/participant from their own point of view. Describe the patient’s path step by step. This also includes waiting times for diagnosis and/or treatment and waiting times for the analysis of the technology.

Take into account all preparations that patients/participants need to make before and after (e.g. diet before bariatric surgery), as well as the need for self/home monitoring.

In addition, take into account the impact of the technology on current pathways of care. It may e.g. shift towards community care or inpatient care.

Common to all used applications

This issue concerns the role of patients/participants. A new technology may require task distribution among the people involved in treatment and care. Patients/participants and their important others and/or caregivers may be more actively involved in their own care and treatment, or otherwise, tasks they used to carry out may be taken over by health professionals.

Specific to Diagnostic Technologies 

Some diagnostic tests are used by patients at home, and patients should be taught how to use them.

Specific to Pharmaceuticals 

The way in which the patient administers the medicine and how he is involved in the follow-up (monitoring by patients/participants or by their important others and/or caregivers).

Specific to Screening Technologies 

The screening needs to be organised in such a way that the test and further investigations are easily attainable; e.g. mobile mammography.

Common to all used applications

A new technology may require new kinds of professionals or new tasks for existing personnel. This issue deals with how the organisation can ensure proper education. Take into account the effect of training on the management and effectiveness

Implementing a technology can change the nature of the work and thus have influence on job satisfaction.

Specific to Screening Technologies

When implementing new screening technologies, proper staff education has to be ensured. For example, when implementing a screening for foetal abnormalities, it takes time to educate nurses and develop their competence in operating the ultrasound.

Common to all used applications

Co-operation and communication is crucial in order to achieve a fluent patient pathway. Implementing a technology can demand new co-operation and communication in and outside the organization, e.g. with other hospitals, pharmacies and manufactures. Therefore structure of co-ordination is important. Also, interaction and communication with patients/participants and their important others and/or caregivers could change. Adaptation of self/home monitoring needs close co-operation and fluent communication.

Specific to Screening Technologies

Screening needs close co-operation and fluent communication between all actors involved in the screening process in all steps (e.g. screening unit, laboratory, hospital, registry, participants). There are actors at different levels which make the communication and co-operation challenging, especially when developing a new screening. The information must be fluent, and electronic communication (software) is crucial. Adequate communication with participants and their important others and/or caregivers must be taken into account.

Different kinds of "patient information" could be defined for screening. For example: (1) "promotional/educational information" with the aim of involving the target population and promoting participation; (2) "screening related information" to communicate with participant the "phase related information" in the different phases of the process (e.g. sending invitation; communicating the test results etc.).

Information strategies should be tailored to the specific subgroup of the target population (depending on socio-economic status, cultural background, epidemiological features, etc.). Risk families need special information.

Common to all used applications

A new technology usually affects current quality assurance not only inside the organization but also outside in different health care levels. To assure quality, a monitoring system with standards and indicators is needed; it is also possible for there to be variation in how the quality assurance and monitoring system is implemented. Take into account who the responsible person for quality assurance and for the monitoring system is, and how any follow up has been arranged.

Additionally, consider how quality assurance and the monitoring system affect management and effectiveness.

Other international, national, regional and/or (cross) organisational demands for quality assurance (e.g. quality standards and monitoring) and for registration could also be in place, and this is another thing to keep in mind.

Specific to Pharmaceuticals

Describe what information has to be gathered (clinical indicators, special patient groups, laboratory results).

There are national standards for Pharmacovigilance of pharmaceuticals. Some countries legally oblige physicians to report the adverse events. In most countries, manufacturers are required to submit all the reports of adverse events they receive from healthcare providers to the national authority. A specific monitoring system may be necessary for innovative pharmaceuticals.

Specific to Screening Technologies

Screening involves asymptomatic participants and quality control is therefore crucial. Quality control needs to be systematic at every step of the screening process and throughout the screening programme. Specify the acceptable delay between screening test to test positive result and finally to treatment. Pay special attention to the control in cases where the programme is provided by several entities (e.g. a combination of private and public health care organisations) and when test and further investigations are separated.

Common to all used applications

The setting (primary - secondary - tertiary care) can vary between different countries depending on the health care system. (De)centralisation could have some economic and qualitative benefits. Centralisation could make the technology more difficult to access. Usually, expensive technologies are centralised to tertiary care units with special educated staff.

Specific to Pharmaceuticals

Report in what health care level the medicine is implemented.

Specific to Screening Technologies

Sometimes, a screening test (for example, a maternal ultrasound) needs specifically trained personnel; this is possible after education/training and a sufficient amount of patients/participants. Centralisation could make screening or further investigation more difficult to access. For example, in foetal screening, timing is important. Decentralisation makes screening more attainable but its quality can weaken.

Common to all used applications

Access to care is often measured in terms of utilisation. There are different viewpoints: individual, population-specific and health system factors. Access to care is related to e.g. social, cultural, economic, organisational, relational or geographical factors.

Access to care by wide definition includes availability, accessibility, accommodation, affordability and acceptability.

This issue is related to the issue of acceptability of new technology (G0010)

Common to all used applications

Implementing the required changes in e.g. hospital premises may be costly for organisations. Starting costs or running costs of a new technology could be very high. High costs can influence the decision on whether to introduce the new technology. Costs can be divided if some organisation(s) is(are) responsible for the acquisition costs and others for the running costs. Take into consideration any investments at all stages of the process.

Specific to Pharmaceuticals

This includes e.g. devices, special room and software needed for the new medicine.

Specific to Screening Technologies

When constructing a new screening programme, there is a need for many investments (e.g. equipment, education and implementation support, training). Take into account e.g. screening program management requirements and sample types which could have critical economic implications. In addition, patient’s preferences and social aspects can influence the compliance rate and thus may have an impact on ECO domain.

Common to all used applications

New (less invasive) interventions may reduce the need for surgical interventions. Some treatments require ongoing monitoring and healthcare visits, including hospitalisation.

Specific to Screening Technologies

Screening tests may cause further diagnostic testing and different treatment due to having detected the disease at an earlier stage.

Common to all used applications

Whenever a technology is introduced, there will be an impact on health care budgets. It is possible to undertake a budget impact analysis which attempts to examine the likely impact of introducing a technology on finances or budgets from e.g. the perspective of different payers. Different payers include: government-level institutions; regions; municipalities; employers; insurance companies and patients/participants. The relevant perspective from which to estimate budget impact may change during different phases of the management process, and incentives are connected to this issue.

For example: What kind of incentives does the budget impact impose on different actors? How might this potentially impact on each organisation? What is the estimated net financial (e.g. annual) cost of introducing the technology? Budget impact analysis provides data to inform an assessment of the affordability of a technology. It also provides a service planning tool to inform decisions about taking the technology into use.

Specific to Screening Technologies

The relevant ‘payer’ can change during the screening process (e.g. a municipality pays for the screening test but then a hospital district pays for further investigations). Screening is usually free of charge for people, but sometimes participants have to pay e.g. a hospital fee for further investigations. Note that when initiating a new screening programme, initial cost outlays may be necessary.

Common to all used applications

The issue concerns the administrative/managerial questions of technology: management of resources (e.g. investments), co-ordination (in relation to different levels and different steps of the process), establishment of objectives, monitoring and control (how quality assurance affects management or effectiveness), evaluation and sanctioning. Take into account the relevant data/information management systems connected to each of these points.

This issue also includes risk management and safety issues (e.g. safety of personnel).

Common to all used applications

Provide information on the key actors who decide on the use of the technology. Do most important decisions take place on the national level (e.g. population screening) or are they, for example, made by individual professionals (e.g. surgical method for a specific disease)? How is the decision made – are there some documented criteria?

Information about the possible variations on the decision level and decision criteria has ethical implications.

This issue may be especially important in the context of rare diseases.

This issue is related to the issue of work processes (G0001).

Specific to Pharmaceuticals

Companion diagnostics (tests or measurements) assist physicians in making treatment decisions for their patients by elucidating the efficacy and/or safety of a specific pharmaceutical or a class of pharmaceuticals for a targeted patient group or sub-groups. Specify and explain how companion diagnostics should be used to identify eligible patients.

Specify the criteria for higher risk groups of patients such as the elderly and children.

Specific to Screening Technologies 

Decisions about people eligible for screening are made in the beginning of the screening. Usually, the decisions have been made nationally or regionally (in municipalities) but also locally (by employers). In systematic screening, the screening unit does not make decisions about who is eligible for screening. The management of positive test results needs systems to guarantee proper follow-up and, sometimes, case specific evaluation. In this topic responsibilities should be identified.

Common to all used applications

Look at acceptance from the perspectives of organisation, personnel, and patients/participants. The organisational view can be separated into the intra-organisational (primary care), inter-organisational (secondary care) and health care system level. Acceptance can vary on different levels and with different actors. Alternative ways to introduce a new technology into an organisation could cause problems such as resistance among staff and dysfunction of processes.

Acceptability is related to access to care.

Specific to Screening Technologies

Acceptance may vary even within one specific screening process; for example, in foetal screening someone might accept an ultrasound but not a chromosomal (serum) test. When describing organisational acceptance, an example would be how sometimes screening may consist of elements which are not suitable for the image of the organisation.

Screening is voluntary, and for persons who are eligible for screening there is no wrong decision, regardless of whether they decide to participate or not. Giving comprehensible information on pros and cons of screening is important, and the staff’s communicational skills may influence a patient to accept screening.

A patient’s/participant’s preferences on screening could influence the compliance rate and thus may have impacts on ECO domain.

Common to all used applications

It may be useful to know who the possible stakeholders are, as well as what kind of co-operation exists and what kind of interaction is needed. The stakeholders could e.g.be the pharmaceutical industry and companies offering technologies for screening, authorities national or regional, registries, administrative parties, municipalities, policy makers/decision makers, staff groups, GPs/primary care physicians and patient organisations. One may also ask: Has the patient organisation taken part into the evaluation process? Has it been involved from the beginning (in the planning) or in the later stages, for example as commentator?

Common to all used applications

• Illness and treatment burden
• Limitations to activities of daily living: work, family, social life, ability to care for oneself, leisure activities
• Psychological issues: stigma, anxiety, fear, social acceptance
• Financial implications, aids needed to support daily living

Common to all used applications

• Improved survival, delayed progression?
• Improvement of specific symptoms (e.g. fatigue, incontinence, diarrhoea, mobility etc.)?
• Improvements/changes related to implications of daily living, social and psychological issues by using the current technology
• What size of effect is important?

Common to all used applications

• What understanding do patients have of the technology?
• What implications – positive and negative – does the technology have regarding activities of daily living, social life, psychological issues, financial implications, support and resources (practical, physical, emotional) and requirement in order for the patient to use the technology with satisfactory results?
• Can the technology be used/taken easily?
• What treatment benefits could be improved?
• What side effects are most difficult to manage?

Common to all used applications

Describe who the important other people are that are involved in the use of the technology, in addition to the patients (parents, children, friends, people at work place etc.). What kind of support (practical, physical, emotional, financial, nurturing, personal) do care-givers mobilize? It includes e.g.:

• What challenges do care-givers face when supporting patients to manage their condition and receive care?
• How do care-givers perceive the new technology; what challenges and benefits might it offer?
• What support and resources need to be mobilised in order for the patient ton use the technology satisfactorily?

Specific to Screening Technologies 

E.g. the results of screening or genetic and prenatal testing, may affect relatives.

Common to all used applications

• Children, older people, certain age groups
• People with a specific genetic mutation, people with disabilities
• People living in remote areas, ethnic groups etc.
• People with a certain type of the disease

Common to all used applications

• Do patients with the condition have good information sources to explain the condition and treatment options to them?
• Are there good decision aids available to help shared decision making between patients and doctors and/or other health personnel?
• Do patients feel themselves involved in a sufficient and appropriate way?

Common to all used applications

• Preparation in advance of intervention, dosage instructions, side effects etc.
• Is there information which patients would need that are not usually available?

Common to all used applications

Describe the rules and recommendations for what patients should know about the implications of using or not using the technology. The right of the patient not-to-know may also be important, as well as the patient's right to complain.

These rules are likely to be helpful for the persons involved in implementing the technology to prepare proper information and counselling. This information may be particularly important with technologies carrying high risks of harm, technologies with the potential to provide information that is not directly relevant to the condition being tested, and in emergency situations in which the patient does not usually have sufficient time to consider the treatment decision.

Specific to Screening Technologies

As screening programs target symptom-free and healthy people, it is particularly important that the individuals are aware of the potential benefits and harmful consequences of attending a screening test. The information provided for individuals attending screening should therefore not be persuasive.

Common to all used applications

According to law, a minor is a person under a certain age, usually the age of majority, which legally demarcates childhood from adulthood. The age of majority depends upon jurisdiction and application, but is generally 18. An incompetent person may be defined as one whose mind is unsound, deranged, or impaired in function, such as a slow I.Q., deterioration, illness or psychosis. What do laws/binding rules require when considering informed consent in these groups? See also I0002.

Common to all used applications

The protection of sensitive personal data is secured at the EU level. Privacy protection is a modern expression of the ancient ethical principle of confidentiality in doctor-patient relationship. The use of computerised patient record databases and modern genetic diagnostics entail certain challenges to this principle. For example, in Z vs. Finland (ECHR February 25, 1997) there was a case of an HIV infected person whose HIV positive test was an incidental finding, not related to her healthcare intervention at the time.

Common to all used applications

A test result may indicate that the relatives of a patient may have a medical condition that would need to be addressed. If this can be foreseen, appropriate procedures, complying with the existing legislation, must be considered beforehand – is the information to be revealed to, or withheld from the relatives in question? Describe on what conditions (if any) the privacy of the original patient can be broken in order to inform the relatives of their situation.

There may be situations, e.g. when treatment malpractice is suspected after the death of the patient, when (closest) relatives demand the results. Similar cases could occur in sudden, unexpected deaths and in some cases of highly infectious diseases.

Common to all used applications

Provide an overview of the legal requirements regarding policies and procedures, as well as examples of: practical local solutions; securing the kind of patient data that will be generated when using of the technology.

Who is allowed to save and store the patient-data, where is it saved, for how long, and who can have access to it? Does the use of the technology produce some additional (i.e. diagnostically or therapeutically irrelevant) information on the patient that could be relevant for, e.g., health insurance, marketing studies, or safety authorities and how should data protection be handled in these cases? Is it possible that legal data protection requirements have adverse consequences to the quality of care, e.g. by complicating the transfer of patient data in a screening process, and how should this be addressed?

Common to all used applications

In general, equality in health care is stipulated in the EU Charter of Fundamental Rights and it is also one of the central principles of the Biomedicine Convention. Moreover, in many national constitutions, equality of citizens also covers access to health care. However, there may be experiences on a national level of some specific difficulties in equal access to the technology, and there may probably also be proposed solutions, which could be helpful for decision-makers in other countries as well.

Common to all used applications

The possible consequences of the EU Directive of cross border health care could be considered here. There may be nationally legally defined processes, including reimbursement and pricing, determining the implementation of and level of access to a technology. This information may give useful insight also beyond one's own country.

Common to all used applications

Describe the register listings, both at EU level and national level, which might be relevant when implementing the technology and planning, e.g., local authorisation, monitoring or evaluation functions, as well as qualification and quality control. Examples include technology registers, registers for marketing authorisation, certification of safety and reimbursement. However, some of the registers, e.g. the one for medical devices (EUDAMED), are not open for HTA doers. Register listings information may be particularly relevant for the technologies which can be used off-label or as investigational intervention outside clinical trials (so-called expanded access or compassionate use).

Common to all used applications

List the legal requirements for safety of the technology and quality of care. Does the technology fulfil these requirements, and what should be done to ensure that the legal requirements maintain fulfilled when implementing the technology? Consider the findings of the SAF and ORG domains here, in the light of relevant European or national safety regulations. See also I0015.

Common to all used applications

This information is important because infringement of intellectual property rights can reduce the use of the technology and have implications for the wording of the acquisition contract of a new technology, and possibly also licencing fees.

Common to all used applications

This issue may help the decision-maker to be aware of their legal rights when considering the manufacturer’s guarantee. The user guide plays a part in determining the manufacturer's liability.

Common to all used applications

Describe the adopted economic measures for controlling public health expenditures when adopting technologies. This information, although not transferable, gives insight to decision-makers in other countries too.

Common to all used applications

Expensive technology and dangerous pharmaceuticals are typically subject to acquisition regulation.

Common to all used applications

Describe general legal principles of the restrictions placed on the marketing of health technologies to lay people.

Common to all used applications

Novel technologies may not always be unambiguously covered by existing legislation. Sometimes, an otherwise restricted technology can be used in clinical trials or as ‘compassionate use’, i.e. in extended use outside clinical trials. Important questions, such as 'How are the liability issues solved according to existing legislation?', or, 'Is the voluntary participation of patients guaranteed properly?' may be important to consider. If the current law does not provide a straightforward answer to the liability issues it may be advisable to consult a legal expert on the interpretation of the existing provisions with regard to the technology in question. Sometimes even new legislative measures are needed.

Common to all used applications

Relevant concerns of partiality or conflicts of interest with regard to binding guidance may give useful insight to decision-makers about the importance of implementing a technology.