Which methodological issue refers to the possibility that the presence of the observer will affect the behaviors of those being observed?

Every day, people with dementia, their partners, close friends and relatives, as well as members of the general public and healthcare professionals, are taking part in research projects aimed at improving in some way the lives of people affected by dementia. The objectives of individual projects differ. Some may be aimed at finding a cure, a better way to treat the symptoms or disease or identifying risk or preventive factors, whereas others may be more focused on improving the quality of life of people with dementia, empowering them, findings ways to provide better support to those who provide care and support, and investigating different care practices.

Here you can find an overview of different topics that are covered in this section. Click on the title to get to the respective part.

Participating in research

This section provides information about:

• reasons to participate in research and possible benefits
• possible drawbacks and risks
• questions to consider asking researchers
• some of the tests that are typically used by researchers
• ethical issues.

What is research?

Research is a general term that covers all kinds of studies designed to find responses to worthwhile questions by means of a systematic and scientific approach. Clinical trials into the safety and effectiveness of new drugs are just one type of research. Other studies, in the domain of dementia, might be aimed at finding out how a procedure could be improved, whether a certain form of social support delays entry into residential care, how people with dementia react to the use of assistive technology, which factors reduce the risk of developing dementia, the impact of dementia on relationships or the ethical implications linked to the use of certain new technologies by or for people with dementia etc.

There are many different ways to carry out research but roughly speaking there are two main approaches, namely qualitative and quantitative. Qualitative studies concentrate mainly on words and meanings and aim to capture the richness and complexity of human experience, whereas quantitative studies involve recording information obtained from participants in numerical form so as to enable statistical analysis of the findings and the generalisation of those findings to the wider population. Behind these two main approaches, there are important theoretical differences and philosophical assumptions about the nature of knowledge, truth and reality, how this should be recorded, what kinds of methods should be used and the role of the researcher in this process. In the past, there was considerable debate about which approach was “right” and some people argued that the two approaches were incompatible. Nowadays, it is generally accepted that both approaches are valid and have their advantages and disadvantages. For this reason, many researchers adopt a pragmatic approach, simply using whichever method is best suited to answering their research questions and nowadays this often involves a combination of both approaches within the same study.

Why do we need research?

A lot of what we do in our daily lives is based on common sense, what we have learnt from other people or what we have learnt through personal experience or observation. But sometimes common sense is not the best approach and sometimes there are conflicting theories about what is best or what works in a particular situation. Moreover, what works in one situation or for one condition might be ineffective or even dangerous in another, or when combined with other measures. Common sense approaches may overlook the impact of external factors which may contribute to what is observed. Even in the domain of healthcare, there are gaps in knowledge, theories about how something might work better and ideas for improvement.

As healthcare professionals cannot afford to take risks, research is needed. For clinical drug trials, this is even a legal requirement in that pharmaceutical companies cannot obtain marketing authorisation (i.e. permission to sell their new drugs) until they have proved to the relevant authorities that the drug is safe and effective. They do this by performing a series of clinical drug trials.

Carefully organised and controlled research enables researchers to test and compare different theories and approaches, explore different methods and learn from other people’s experience. It also enables them to rule out or at least consider external factors which might influence their results. For example, before concluding that drinking green tea is good for X, Y or Z, it is important to ensure that the tea drinkers studied do not have something else (i.e. other than drinking green tea) in common such as being more physically active than non-tea drinkers or being vegetarians, which might equally explain the findings.

Another advantage to carrying out research is that for a lot of studies, the findings can be recorded numerically and then statistically analysed in order to determine whether the findings are significant (i.e. the extent to which it can be claimed with a specified degree of certainty that they are not just due to chance). With quantitative studies, the results can usually be generalised to the wider population (e.g. to people affected by dementia, GPs or lay people in general, depending on the group studied). This is because measures would have been taken to ensure that the group of people who took part in the study were, as far as possible, representative of other people in that category (e.g. not all White, highly educated men or women from a relatively small geographical area but rather people who have a range of characteristics that are typically found in the broad group of people that the research is about).

The advantage to many qualitative studies is that they permit an in-depth investigation into a particular aspect of human experience. They give people the opportunity to explain in their own words how they feel, what they think and how they make sense of the world they live in. Whilst it is not possible to make generalisations about a wider group based on a small qualitative study, in some cases the results may be transferrable to other similar situations or groups. However, the advantage to qualitative studies is that they provide rich, meaningful data and insight into the complexity of human experience with all its contradictions, differences and idiosyncrasies. Some address topics which have not previously been researched and may even deal with controversial, sensitive or taboo issues. Some studies also serve to give a voice to vulnerable or minority groups (which is a key feature of advocacy/participatory research).

Who can take part in research?

All kinds of people are needed to take part in dementia research including, for example, people with dementia, members of the general public, providers of social support and health care professionals.

There may be conditions for taking part in a particular study (e.g. based on age, state of health or living arrangements) which are determined by the objectives of the research. Usually, these conditions are justifiable and necessary for the researchers to find answers to their research questions (e.g. in the case of a study into the impact of hormone replacement on the risk of women developing dementia being limited to female participants). However, some conditions are not justifiable and would constitute discrimination. Ethics committees, which are responsible for ensuring that research is fair and right, try to ensure that any conditions or restrictions are justifiable from a research and ethics perspective.

The involvement of people with dementia in research should not be limited to their participation in clinical trials nor to the involvement of people who only have mild cognitive impairment. Whilst there are ethical and legal issues to consider (please see section on consent) and researchers will need to pay particular attention to the possible communication and memory difficulties of the participants, these are not valid reasons to exclude people with dementia from other forms of research. In addition to sharing their personal experience of what it is like to have dementia, people with dementia can be involved in all kinds of research such as studies which evaluate service provision, the development of guidelines, consultations regarding policies and working groups on a wide range of issues such as legislation, ethics, care, stigma and diagnostic procedures, to name but a few. They can also be involved in the planning and organisation of studies, as well as in the analysis and interpretation of the findings of some studies. It is up to researchers to find innovative and creative ways to enable people with dementia to express their views and share their experience.

Benefits of taking part in research

Most of us have in some way benefited from research without necessarily realising it (e.g. by taking medical drugs, benefiting from the use of certain equipment, being treated in a certain way or being in a certain environment). People who take part in dementia research are contributing towards the care, treatment and wellbeing of countless numbers of people who have dementia, as well as others who may develop it at some time in the future. They may have different reasons for wanting to be involved in research and different expectations about what it might bring. Examples include:

• To contribute towards the advancement of science
• To take an active role in their own healthcare
• To help combat feelings of helplessness
• To do something interesting
• To exercise their autonomy and take an active role in society
• To have the possibility to test an experimental drug or access treatment that is not yet widely available
• To receive high quality, free healthcare from leading experts during the trial
• To improve one’s own condition, wellbeing or quality of life

Researchers as well as ethics committees are keen to ensure that participants are treated well and that their safety and wellbeing are respected. There are, of course, pros and cons to participating in research which people should consider before agreeing to take part in a study. Some are general and some are linked to specific types of study. However, generally speaking, participating in research should be a positive experience and participants should always be given the name of a contact person whom they can contact should they have any concerns or complaints about how they are being treated or about the study.

Potential risks and burden linked to taking part in research

It is important when volunteering for clinical trials to be realistic about the possibility of the experimental drug proving effective and becoming rapidly available. Researchers are likely to be enthusiastic about their topic of research and expect it to prove beneficial to people with dementia in the long run but research by definition involves a degree of uncertainty (otherwise there would be no need to carry out tests). Most importantly though, the aim of research is not to benefit the participants even though participants often feel that they get something positive out of participating.

In clinical drug trials, for example, whilst the experimental drug may have a positive effect on some research participants, the whole process of drug development from the initial discovery of a potentially effective substance or molecule to marketing of the drug can take several years. Many participants involved in the trial will not even receive the experimental drug (as they will be in the control group which receives a placebo). Some of those who do receive it, may experience unforeseen side effects which may be unpleasant, serious or even life-threatening. In “double-blind placebo-controlled clinical trials” participants do not know whether they are receiving the experimental drug or the placebo. Neither do the researchers until the end of the trial so they cannot inform participants during the trial. This is a careful and strictly controlled procedure and often considered one of the highest quality methods of research but it can be frustrating for some participants.

On the other hand, anti-dementia drugs that are currently available were dependent on people taking part in clinical trials. The continued participation of people with dementia in such trials is essential for the continued development and improvement of drugs to treat and perhaps even one day to prevent or cure dementia.

Some studies may involve a certain degree of inconvenience or burden. Examples include:

• Having to fill out lengthy forms and questionnaires
• Having to stay in hospital for a while
• Having to be available for several visits, perhaps at inconvenient times
• Having to travel to where the research is being carried out
• Being observed or monitored
• Loss of privacy e.g. having interviewers in your home
• Being asked about or reminded of very personal issues
• Following strict instructions e.g. with regard to behaviour, exercise or diet
• Being subjected to various tests e.g. blood tests, scans, computerised tests involving reaction times or memory etc.

The above examples would probably not be disturbing to most people or particularly unpleasant. It is more a question of inconvenience and knowing in advance what is involved so as to be able to choose a study that suits your character and can fit into your daily routine.

Many studies nowadays require participants to have a study partner. This person is asked to accompany participants to meetings with researchers, help ensure that they comply with the researchers’ request (e.g. to do certain tests or report back information) and/or provide information about the participant (e.g. filling out questionnaires about their daily behavior or mood). Often, the study partner is a partner or close friend of the participant and it might be something interesting that they do together. However, that person also has to commit to being involved and is usually considered as a research participant themselves. Being a study partner requires time and effort. The study partner might not have the same level of interest in participating and some may find their involvement a bit of a burden. The need to have a study partner can be an obstacle to people who live on their own or who do not have someone who is willing to do that. Those people may find themselves excluded from research which is an issue that needs to be addressed by researchers .

Is research always worthwhile and how can people find out about the results?

An experimental drug would not have reached the clinical testing phase unless there was already strong evidence to suggest that it would prove at least as good as existing treatments, if not better. Research should always be based on a prior in-depth understanding of the issue to be researched, building on previous research, backed up by sound theories and approved by ethics committees. Research should always be based on questions that are worth asking even if, as in the case of students, part of the aim of conducting the research is to acquire research skills.

Participating in research is always constructive in some way as it adds something to existing knowledge. Even if an experimental drug proves ineffective or results in undesirable side effects, this newly acquired knowledge will contribute towards developing a new, more effective and safer drug. Similarly, finding out that a new or commonly accepted approach to care does not improve quality of life may result in it no longer being used or an alternative approach being investigated and thus benefit the lives of many people.

For this reason, it is important for researchers to document the results of all studies and to make details of the findings publicly available. Researchers are increasingly being encouraged, in some cases obliged, to make the findings of their research available, not only in peer-reviewed scientific journals but also in places that are accessible to a broader audience. Many research funders now require researchers to publish in open access journals which do not require access to university libraries or require expensive subscriptions. Researchers are also increasingly encouraged to keep research participants and those involved in Public Involvement informed about how the research is progressing and the overall results at the end of the study.

Questions to ask about research

The kind of study and the goals of the researchers will determine to a large extent what is expected of participants. However, irrespective of the precise nature of the study, the researchers will have a clear plan of what they want to do, how, when and for how long. This is called the research protocol. These issues should have been discussed with participants and informed consent obtained prior to the start of the study. However, in order to give informed consent, participants must have received and understood all the relevant information linked to the proposed study. It is the researchers’ responsibility to provide such information and to ensure that participants have understood it. Participants are free to ask for further clarification and information, and should be encouraged to do so. The following box contains examples of questions that people might want to consider asking before consenting to take part in research.

Purpose of the research

• Why is this study/trial being conducted?
• What do the researchers hope to discover?

Procedure

• What is involved (e.g. hospital stays, visits to the doctor, injections, blood tests and scans etc.)?
• Is any of this likely to be stressful, uncomfortable, burdensome or painful?
• What is the likelihood that I will receive the experimental drug (in the case of clinical trials)?
• How long will the study/trial last?
• Where will I have to go and how often?

Benefits and risks

• Are there any benefits or risks involved in this study?
• Am I likely to benefit personally from participating in this study?

Consent

• Will I be provided with support if I have difficulty understanding all the information provided?
• Will I still be able to participate in research if I am considered unable to provide informed consent?
• What are my treatment or care options if I decide not to participate in this study?
• Can I withdraw at any time?
• Will my wish to withdraw be respected even if I am considered as lacking decision-making capacity at the time?

Continuing care

• How will participation in this study/trial affect my current care?
• How will participation in this study/trial affect my future care?

Safety

• What are the likely side effects, if any?
• What will happen if I experience side effects?
• What will happen if the researchers notice something abnormal in the information they collect about me that is not directly linked to their study but relevant to my health?
• If anything goes wrong, would I be covered by some kind of insurance?
• Who is responsible for the safety and wellbeing of participants?
• Whom can I contact in case of emergency or if I wish to complain?

Confidentiality

• Who will be informed that I am participating in this study?
• Who will know whether I am receiving an experimental drug?
• Will personal information about me be kept on a computer or in a report?
• Will I have access to information that is collected about me?
• If so, will my anonymity be respected?
• Would I be bound to secrecy in any way?
• How will the results of the study be presented and used?
• Will anyone see my name and information about me in the reports of the research findings or will it all be anonymous?
• Will I be informed of the results of the study afterwards?

Payment

• Is there any payment to compensate participants for their time and effort?
• Are travel costs and other related expenses covered?
• Does anyone receive compensation of any kind for my participation in the study?

Restrictions

• Is there anything I should or shouldn’t do during the study?
• Can I also take authorised drugs for dementia during the study?

Tests used in dementia research

At the beginning of the study and at various points throughout, participants are usually asked to undergo various tests and examinations and to comply with various procedures. Some of these are paper-and-pencil tests or computerised tests, some involve filling out questionnaires or being monitored/observed. Others involve taking samples or undergoing procedures to detect biomarkers (measures of what is happening inside the living body). This includes blood and urine samples, cerebrospinal fluid (obtained by a lumbar puncture/spinal tap) and various brain scans. However, participants are under no legal obligation to have these tests, irrespective of any forms they may have signed, and they can withdraw from the study at any time (please see section on ethical issues).

In dementia research, cognitive tests, as well as tests to measure the ability to carry out daily tasks, are quite common. This is because researchers need to be able to measure the impact of a particular intervention. That could, for example, be a drug, the provision of a service or a lifestyle change, such as exercise, stopping smoking or adopting a healthy diet.

In this section, details are provided of some of the tests (sometimes called tools) that are commonly used by researchers. There are numerous tests and these are just a few examples of different kinds. It should be noted that tests are sometimes culturally biased which means that people from minority ethnic groups do not perform well on them. This is discriminatory and also means that the tools do not provide an accurate measure of everyone’s performance and hence lead to unreliable results for the study. For more information about the issue of cultural bias in testing materials, and examples of several assessment and diagnostic tests (some of which are used in research), please see Chapter 6 of our 2018 report on Intercultural care and support at: https://www.alzheimer-europe.org/resources/publications 

Alzheimer’s Disease Assessment Scale (ADAS) and Alzheimer’s Disease Assessment Scale - Cognition (ADAS-Cog)

The Alzheimer’s Disease Assessment Scale (ADAS) (Rosen et al. 1984) is a two-part scale designed to assess cognitive and non-cognitive symptoms of Alzheimer’s dementia. It is one of the most frequently used scales in clinical trials but is quite time-consuming (taking 40 to 45 minutes for a trained interviewer to administer).

The part which measures cognitive faculties is known as the ADAS-Cog. There are 7 performance items and 4 clinician-rated items coving memory, orientation, language and praxis. Possible scores range from 70 (severe impairment) to 0 (no impairment). The part which measures non-cognition contains 10 clinician-rated items covering agitation, depressed mood, psychosis (delusions and hallucinations), attention/concentration and changes in weight. It is not generally used for the assessment of people with severe dementia.

The Mini-Mental State Examination (MMSE)

The Mini-Mental State Examination (MMSE) is a measure of cognitive function which was originally designed as a screening tool. It is perhaps the most widely used measure of cognitive function in the world and it is also used by researchers. It consists of 11 items designed to evaluate orientation, memory, attention, language and motor skills. Possible scores range from 30 (severe impairment) to 0 (no impairment). People with Alzheimer’s disease not receiving treatment tend to decline 2 to 4 points per year on the MMSE (Schneider, 2001). However, the MMSE is less sensitive to progressive decline in people who already have very low scores. A cut-off score of 23 for the presence of cognitive impairment has been suggested although this may vary slightly depending on the patient’s level of education (Burns et al., 2002). The MMSE is easy to administer and only takes about 5 to 10 minutes to complete.

Montreal Cognitive Assessment

The Montreal Cognitive Assessment was originally developed to help screen for mild cognitive impairment (MCI). It is easy and quick to administer (it takes about 10 minutes), and has been widely translated.  t assesses attention/concentration, executive functions, conceptual thinking, memory, language, calculation and orientation. The maximum score is 30. A score of 25 or under indicates significant cognitive impairment. According to Sheehan (2012), it is particularly useful for people with vascular impairment, including vascular dementia.

Activities of Daily Living Scale (ADL)

The Activities of Daily Living Scale (ADL) was developed by Katz in 1963. It is used to assess the level of a person’s physical functioning and is generally considered an accurate measure. A person’s ability to accomplish a range of tasks without assistance is evaluated. The six basic activities are: 1. bathing, 2. dressing, 3. toileting, 4. transferring (i.e. getting in and out of bed or a chair), 5. continence and 6. feeding. Whilst they are very practical tasks, they all require a certain degree of cognitive functioning as tasks need to be planned, things organised, objects recognised and correctly used and choices made etc.

Instrumental Activities of Daily Living Scale (IADL)

In 1969, Lawton and Brody designed the Instrumental Activities of Daily Living (IADL) Scale which was aimed at evaluating more complex activities of daily life. The patient’s capacity or incapacity to accomplish various tasks provides evaluators with a kind of proxy measure of that person’s cognitive abilities. Whilst the tasks seem very practical, they require a higher degree of cognitive functioning than those covered by the ADL scale. There are divided into eight categories: 1. ability to use the telephone, 2. shopping, 3. preparing food, 4. housekeeping, 5. laundry, 6. transportation, 7. managing own medication and 8. ability to handle finances.

Within in each section, there are various activities for which points are attributed. For example, in the section on transportation a point is given for each of the following: travels independently on public transportation or drives own car; arranges own travel via taxi, but does not otherwise use public transportation; travels on public transportation when accompanied by another; but no points are gained for: travel limited to taxi or automobile with assistance of another; does not travel at all.

Disability Assessment for Dementia (DAD)

The Disability Assessment for Dementia (DAD) scale is designed to measure functional abilities related to basic and instrumental activities of daily living. It contains 40 items and takes about 20 minutes to complete.

Neuropsychiatric Inventory (NPI)

The Neuropsychiatric Inventory (NPI) is a short test which is used to assess behavioural and neuropsychological disturbances in people with dementia. It measures a range of symptoms including delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, aberrant motor activity, apathy, irritability, night-time behavioural disturbances and eating disturbances. The severity and frequency of symptoms are measured separately.

Quality of Life in Alzheimer’s Disease Patient and Caregiver Report (QoL-AD)

The Quality of Life in Alzheimer’s Disease Patient and Caregiver Report (QoL-AD) is used to assess quality of life and is based on reports provided by people with Alzheimer’s disease and their carers. The scale contains 13 items, each marked on a 4-point scale. The areas covered are mood, physical health, memory, relationships, self-esteem and current situation.

Clinical Dementia Rating (CDR)

The Clinical Dementia Rating (CDR) is a global measure of dementia, which is usually completed by a clinician by means of an interview with the patient and the carer (which takes about 40 minutes). The clinician may already have gathered much of the information in the course of their previous contact with the patient.

The CDR provides a means to categorise people with dementia according to stages. A score of 0 would indicate no dementia and 0.5, questionable dementia, whereas a score of 1, 2 or 3 would be an indication of mild, moderate or severe dementia (Burns et al., 2002). Six areas are covered i.e. memory, orientation, judgement and problem-solving, community affairs, home and hobbies, and personal care.

Brain scans

Computerised Axial Tomography (often abbreviated to CT scan or CAT scan) is a type of scanning which allows researchers to detect shrinkage of the brain (which can also occur in people who do not have dementia). It can also serve to help differentiate between vascular dementia and Alzheimer’s disease. The scanning process involves taking pictures of slices of the brain by means of X-rays and a computer. A harmless dye may be injected to make the images clearer. The scanning takes about 15 to 30 minutes and is not painful or disturbing (i.e. no loud noises). However, the person needs to remain still during the process. For this reason, if a person is slightly agitated, he/she may be given a light sedative. (Source: Royal College of Psychiatrists, 2009).

Magnetic Resonance Imaging (MRI) is another type of scanning which takes pictures of the brain but not using X-rays. It provides more detail than CT scans and is also more expensive. MRI detects radio signals in the body which are produced in response to the effects of a powerful magnet contained in the scanner. The scanner is very noisy and whilst the whole process is painless, it may take up to an hour. It can be fairly uncomfortable to remain completely still for so long.

Single Photon Emission Computerised Tomography (SPECT) is a scan which measures blood flow in the brain. The patient is given an injection of a very mild, harmless radioactive substance (radionuclide) which travels in the blood to the brain. The pictures from the scan show slices of the brain and indicate the extent to which different parts of the brain have taken up the injected substance. This serves as a measure of how effectively blood is reaching different parts of the brain. The person has to sit still during the scanning procedure, which takes about XX minutes.

Positron emission tomography (PET) produces a three-dimensional picture of functional processes within the body (e.g. blood flow, oxygen use or glucose metabolism) using radionuclide as a tracer. The images obtained are usually reconstructed by means of a CT X-ray scan which is performed at the same time as the PET scan. The PET scan may use fluorodeoxyglucose (FDG) in order to measure regional glucose uptake. The tracer may be injected, swallowed or inhaled. After receiving it, the person may have to wait for about 30 to 60 minutes whilst the tracer travels through the body before the actual scanning (which takes 20 to 30 minutes) takes place (Source: Wikipedia, 2009 and www.radiologyinfo.org, 2009).

Ethical issues

Informed consent

The necessity to obtain informed consent

Before anyone participates in a study, they should have given their informed consent to the researchers in charge of the study. Giving informed consent involves more than just accepting to take part as the decision must be based on a full understanding of what is involved. The information concerning the study should be provided by the researchers and be understandable to potential participants who should be given time to take in the information, discuss with other people if they wish to do so and ask any questions. For this reason, informed consent should be seen as a process rather than simply a document to be signed.

For studies involving medical treatment or drugs, the consent procedure is a medico-legal requirement covered by laws and codes of medical ethics. Depending on the country in which the research is being carried out, there may be additional specific laws on research which lay down conditions for obtaining consent. People with limited mental capacity or who lack the capacity to consent may still participate in research under certain conditions (which may be fairly strict).

The procedure

People who are considering taking part in a study are sent detailed information and a formal document to sign. They are usually invited to a meeting with the researchers to discuss their possible participation and are free to bring along another person (e.g. their doctor, a social work, a legal representative, a close friend, relative or another trusted person) and to ask questions. Sometimes, the researchers have brochures or DVDs which people can take home and look at before making a final decision. This gives them the time to make sure that they fully understand what is involved, to discuss the matter with friends and family and to think about any additional questions they may have.

It is the researchers’ responsibility to ensure that potential participants fully understand what is involved as this is the basis for informed consent. Once the study is underway, the researchers may acquire additional information which might affect whether some participants would want to continue or would prefer to withdraw. The researchers should share such information with participants.

For questionnaires or surveys, the situation is sometimes different as the researchers do not necessarily have direct face-to-face contact with the participants e.g. in the case of random postal surveys. Participants’ consent is implied by their action in returning the completed questionnaire as invited. However, the researchers should have provided background information about the study and how the information obtained will be used either on the questionnaire or in a cover letter.

The fact that a person has consented to a face-to-face interview does not necessarily imply that they have also consented to being filmed or recorded. It is therefore important that researchers ask additional consent to use recording equipment during an interview.

Most research ethics committees require written consent (i.e. with a real signature) for any research involving direct contact with participants (e.g. one to one or in a group) conducted by telephone, in person or virtually. More recently, perhaps especially due to the COVID-19 situation when people were unable to go out (e.g. to post letters), some research ethics committees accepted various forms of virtual consent. It is important to develop new and innovative approaches to informed consent that are appropriate for people with dementia and taken into consideration the challenges they face. For some approaches, participants may need additional support.

The ability and right to decide whether to participate in research

The aim of informed consent is to protect research participants from harm whilst respecting their right to decide for themselves whether they would like to take part in a particular study. The informed consent procedure should give people the opportunity to weigh the possible benefits against the burden and risk of participating in research. It must ensure that any consent given is voluntary (i.e. people have not been forced or pushed into participating against their will).  Participants must also have the capacity and the legal right to make that decision (i.e. decision-making capacity and legal capacity).

People may have varying degrees of decision-making capacity. This may fluctuate not only because of dementia but also due to a range of psychosocial, emotional, situational, medical, psychiatric and neurological factors. Researchers need to determine whether a potential participant has the capacity to consent to participation in a particular study. Lack of such capacity does not automatically result in a person’s exclusion from research. Many people with dementia are able to give informed consent if appropriate adjustments are made and necessary support provided.

Many people who are in the early stages of dementia have the capacity to consent to participation in research. However, it is important that researchers understand that people with dementia may have certain difficulties with comprehension, attention span, memory and communication. For this reason, researchers need to take extra care to ensure that the information they have given has been understood and to respect each person’s pace. Printed information can be helpful as a support to memory and going back over what has been said can help the person remember what is involved. Involving a someone of the person’s choice can also be helpful provided that the person with dementia agrees to this.

Assessment of the capacity to consent

Informed consent should not be understood as a signed piece of paper or a one-off requirement at the beginning of a study. Rather, it is a process based on verbal, non-verbal and behavioural cues, which needs to be revisited regularly throughout the research. A range of approaches can be used to obtain informed consent for participation in research such as clinical interviews, discussions and measures of capacity, including neurological test batteries (Beattie 2009).  The MacArthur Competency Assessment Tool for Clinical Research (MacCAT-CR) (Appelbaum 2007, Appelbaum and Grisso 2001) is sometimes described as the ‘gold standard’ for the assessment of capacity to consent to clinical research, although not necessarily on its own (Howe 2012). It covers understanding, appreciation of the nature of the situation, reasoning and expressing a choice.

Examples of other instruments include the University of California San Diego Brief Assessment of Capacity to Consent (UBACC) and the Evaluation to Sign Consent (ESC) (Beattie 2009). The Mini Mental Status Exam (MMSE) is not generally considered as a suitable or reliable measure of the capacity to consent to research. Care should be taken when drawing conclusions about capacity to consent using instruments which have not been validated for people from various minority groups.

Being informed vs understanding

Information provided to potential research participants with dementia should cover various issues related to a particular study (e.g. what the study is about, why the person is being asked to participate, what participation would involve, potential risks and possible benefits if any, who is responsible for the study, the timeframe of the study and whom to contact for more information, further explanation or in case of complaints) and general issues related to participation in research (e.g. the voluntary nature of participation, the right to withdraw at any time, confidentiality and privacy issues). Participants must be able to comprehend the information provided, demonstrate that they have understood, assess the relevance of information to them and make a reasoned decision.

Voluntariness and the therapeutic misconception

Participation in research of any kind must be voluntary. There are different degrees of lack of voluntariness ranging from being subjected to research without having had any choice in the matter, being forced to participate on the basis of some kind of threat or deciding to participate on the basis of undue influence. Pressure to participate can be quite subtle and may be unintentional. An example would be someone being asked by a healthcare professional or staff in a residential care setting and fearing upsetting that person due to a feeling of dependency on them, respect for their position or not wanting to jeopardise an existing positive relationship with them.

People’s voluntariness could also be influenced by their interpretation of what they are being asked to do and why. The decision about whether or not to participate in research may depend on how research is understood and most importantly, whether a person understands the difference between research and treatment or care. This might not always be as obvious as it first seems, especially in situations where a person is informed about a study by a healthcare professional in a healthcare setting (Lewens 2006). The provision of treatment and care is generally consented to on the basis of an assumption that it is necessary and will hopefully in some way be personally beneficial. If this distinction is not clear, it cannot be said that a person has given informed consent to research. Medical researchers should try to ensure that potential participants realise that the overall aim of research, including biomedical research, is not to improve their health or contribute to their personal wellbeing. The overall aim is to generate new knowledge that will be beneficial to society.

Consent with and on behalf of people with dementia: shared, supported and proxy decision making

There has been a move away from the concept of proxy (i.e. substituted) decision making towards supported decision making. Supported decision making is about providing the necessary support to enable a person to make a decision, including one that is legally recognised.

In their recommendations on research (and data sharing) involving people with dementia, Thorogood et al. (2018) point out that research ethics guidelines generally promote supported or shared decision-making.  They suggest that this might include “simplifying consent forms, providing visual or memory aids, taking interactive or educational approaches (where persons with dementia are asked to explain their understanding of consent elements), re-explaining misunderstood information, or involving familiar carers to facilitate explanation and communication of a decision” (Thorogood et al. 2018, p.1338). Such measures could perhaps be further extended to address any barrier experienced by people with dementia, regardless of whether it is linked to a health condition (e.g. such as having a lower level of literacy or being a member of group that is stigmatised etc.).

In situations where a person has been appointed who is authorised to decide on behalf of a person with dementia about participation in research (i.e. a ‘proxy’ or ‘substitute’ decision maker), it is increasingly excepted that that person should base their decisions on the known will and preferences of the person with dementia and not on the basis of ‘best interests’ or ‘welfare’ (Thorogood et al. 2018). Where possible, people with dementia should, as far as possible, be included in the decision-making process. In addition, even people evaluated as unable to give consent for research may preserve the capacity to appoint a research proxy (Kim et al. 2011).

It is increasingly recommended, if not stipulated (European Directive 2001), that proxy consent should represent the person’s presumed will. In reality, this is often not the case. Proxies often do not know a person’s will and preference and make decisions that the person appointing them would not have made (Kim et al. 2013, Thorogood et al. 2018). Proxies may sometimes be too restrictive, thus depriving people with dementia of the opportunity to be involved in research or, on the contrary, involve people with dementia in research when this does not correspond to their wishes, values and interests (Jongsma 2016).

Proxies can be very beneficial in combination with advance directives because they may be well-placed to help interpret the kinds of studies a person might have wanted to participate in, drawing on the information provided in an advance directive, their knowledge of the person and possible information about his/her wishes and interests. Some people with dementia grant their proxies the power to override their previously expressed wishes (e.g. in the light of scientific advances which result in unanticipated consequences for participation or on significant changes in the person’s situation). Others may want their advance directives to be followed, without leaving leeway for their proxy to decide.

Substitute decision makers (whether they be healthcare proxies, legal guardians or relatives) could also discuss the issue of research with the person with dementia, speak to the researchers about interpretation of the advance directive, monitor the research process and signal any problems. However, it must be borne in mind that their views about research may differ to those of the person they are representing. They may be over-protective or simply unaware of what the person with dementia would have wanted. Moreover, they are supposed to act in the person’s best interests or at least not act against them, which would be problematic in the case of non-therapeutic research involving more than minimal risks and/or burdens (as they may consider any risk or burden as not being in the person’s best interests). For this reason, it is important that when people designate a health care proxy, they discuss their preferences and feelings about different types of care with him/her, and any views about participation in research.

Consent by means of advance directives for research

Whilst it is often not possible to obtain consent to research from people in the late stage of dementia, there is a need to balance their protection with their right to choose to participate in research, should they wish to do so. One solution is to encourage people in the early stages of dementia to consider this issue and record their wishes in an advance directive. Alternatively, they could record their wish not to take part in research. In most countries, such statements about research would not be legally binding but, as an example of previously expressed wishes, could be taken into account in any discussions about possible participation.

Writing an advance directive for care/treatment is more straightforward than writing one for research. For the former, the person can refer to specific known interventions or use more general terms such as “all life-saving interventions” whereas for the latter, it is difficult to give consent for a future experiment which has not yet been devised and which by the nature of research is likely to be innovative. Furthermore, it would be difficult to formulate wishes in terms that are neither too vague nor too restrictive. In view of the amount of time that could pass between making the advance directive and the research starting, it is difficult for someone to have a clear idea of what they might be letting themselves in for.

Several ethical concerns have been raised about the use of advance directives in the context of dementia (in general, not necessarily for research). These are mainly linked to arguments about personal identity and changing interests. There is a broad and complex philosophical debate surrounding personhood and dementia. An issue of particular concern and of relevance to the debate about advance directives for research is whether the person who wrote an advance directive is the same person as the one for whom it may later be applied, and if not, why the advance directive should be respected. This is a complex philosophical debate. For further reflection on this issue, please see Alzheimer Europe’s 2019 report on Overcoming ethical challenges affecting the involvement of people with dementia in research and our earlier report of 2009 on Advance directives, both of which can be downloaded at: https://www.alzheimer-europe.org/resources/publications

Consenting to future research in an advance directive is also problematic because, as pointed out by Berghmans (1998), it is difficult to give consent for a future experiment which has not yet been devised and which, by the very nature of research, is likely to be innovative. Researchers may find it easier to accept a negative advance directive for research as this does not raise issues about the ambiguity surrounding the risks and burdens people might be exposing themselves to. The risks of research as well as the potential burdens and benefits can only ever be estimated but in the case of decisions made for research that might occur several years later, procedures and methods may have advanced beyond what was initially imaginable.  The ‘informed’ aspect of consent is therefore missing in the case of advance directives for research. However, people can be informed about and helped to understand the implications of this lack of prior knowledge and then make as informed a decision as possible. Those who have a trusted person could be encouraged to appoint and allow the involvement of a proxy in future decisions about participation in research.

Confidentiality

People participating in research are entitled to confidentiality even if the results of research are made public. Information should not be divulged to anyone outside the research team unless prior authorisation has been obtained. In most cases, anonymity is guaranteed and participants may be assigned code names or numbers. This enables the researchers to quote people without revealing their true identity. Moreover, any personal/private information that researchers learn of in the course of the study, which is not related to the study, should not be disclosed to anyone. There is a difference between anonymisation and pseudonymisation. With anonymisation, participants are assigned a number or code which is linked to the data that they provide but the code cannot be traced back to them (e.g. to their name and address), whereas with pseudonymisation, it is stored and could at some point be traced back to them (even though it usually isn’t).

In some studies, particularly small-scale qualitative studies or action research, researchers may decide to show the preliminary results to the participants and invite them to comment. This gives them the opportunity to confirm or query anything that has been written about them as well to be more fully involved in the study. This is very important in studies which have involved very personal contact or with participants who have shared very personal information about themselves. It is also important from a scientific perspective as a means for researchers to check that they have fully understood the information that was communicated to them.

For a comprehensive overview and discussion of ethical issues linked to the involvement of people with dementia in research, please see our 2019 report on Overcoming ethical challenges affecting the involvement of people with dementia in research at: https://www.alzheimer-europe.org/resources/publications

Research Ethics Committees

Most countries have research ethics committees to which researchers must apply for approval before starting their research. Research ethics committees may be governmental, independent, linked to local health authorities or linked to educational institutions. Depending on the kind of research being carried out and the participants involved, researchers may have to seek approval from more than one committee. The approval is usually granted on the basis of a detailed description of the planned research, containing details of the methods to be used, the people to be involved, the kind of analysis to be carried out, evidence of the scientific justification for the study, ethical issues envisaged and methods to be adopted so as to avoid participants or even researchers coming to any physical or psychological harm. The committee may also invite the researcher to a meeting to discuss certain issues. Increasingly, research ethics committees include a person with dementia.

In some cases, ethical approval is a legal requirement, whereas in others it is an academic requirement. Some researchers would not have access to such research ethics committees but would nevertheless be expected to have considered relevant ethical issues and to have obtained informed consent from all participants.

Different approaches to research

Research could be described as a systematic, organised attempt to find answers to worthwhile questions, using predefined methods or procedures which are clearly documented. It should be possible for other people to understand exactly what the researchers did to arrive at their conclusions. In this way, the results and conclusions can be assessed and analysed in terms of relevance and accuracy, bearing in mind any limitations or factors which the researchers may have highlighted.

Research is guided by theories. It builds on knowledge that has been acquired from previous studies with the aim of going one step further or responding to an observed lack of research into a particular issue. Theories, drugs and medical procedures are tested, people’s experiences are explored and new issues are uncovered and addressed. In the healthcare domain, the issues tend to be those which are important to the general population or to specific groups of people (e.g. patients, carers, healthcare professionals or policy makers).

A distinction may be made between the theoretical and empirical aspects of research. Theoretical research involves developing, exploring, testing and refining theories, whereas empirical research involves observing and measuring what actually happens.

This section provides details of philosophical assumptions behind research, a description of differences between main types of research (e.g. qualitative and quantitative) and details about different methods used (e.g. interviews, questionnaires, experiments, observation and long-term monitoring etc.)

Philosophies guiding research

Researchers have different world views or belief systems which guide them in their research, influencing the decisions they make about how to conduct their studies, what counts as valid knowledge, what is the right way to obtain that knowledge, how it should be analysed (e.g. using quantitative or qualitative-based methods) and what their own role in the process is. The various approaches to research are sometimes called research paradigms. The whole issue of paradigms can be traced back to Kuhn’s 1970 influential book “The Structure of Scientific Revolutions”.

For quite some time, the two main paradigms were the positivist/postpositivist paradigm (linked to quantitative research) and the constructivist paradigm (usually associated with qualitative research). A few decades ago, there were huge methodological debates as to which of the two paradigms was right. Some researchers argued that only the positivist/postpositivist paradigm was “real science”. Others argued that it was not suited to the study of complex human and social issues. This debate came to be known as the paradigm wars and there was an “incompatibility theory” which stated that the two approaches were irreconcilable due to their very different underlying philosophies.

The postpositivist tradition emerged in the 19th century based on the work of writers such as Compte, Mill, Durkheim, Newton and Locke. They challenged the positivist attempts to seek “absolute truth” arguing that this was not appropriate when studying the behaviour and actions of people. This led to an acceptance that absolute truth can never be found and that research evidence is not infallible or perfect. Researchers attempt to look for and describe associations, as well as cause and effect relationships. This is an ongoing process, whereby positive findings form the basis for additional research. Data which does not support their theory may result in necessary revisions followed by additional testing.

According to the social constructivist paradigm, people try to make sense of the world they live in. Through interaction with other people, they develop subjective understandings and meanings of their experience and they do this within a specific social, political, cultural and historical context. Social constructivists believe that there is not one reality but rather varied and multiple realities. Based on this theory of reality, researchers are interested in trying to understand the way people experience and make sense of the world.

However, there were also arguments in favour of a compatibility theory which acknowledged the different philosophical assumptions but stated that each approach had its strengths and weaknesses, that neither was right or wrong and that methods typically used by each could even be mixed in the same study. This is known as the pragmatic paradigm.

The three main approaches

Quantitative research

Quantitative research is generally associated with the positivist/postpositivist paradigm. It usually involves collecting and converting data into numerical form so that statistical calculations can be made and conclusions drawn.

The process

Researchers will have one or more hypotheses. These are the questions that they want to address which include predictions about possible relationships between the things they want to investigate (variables). In order to find answers to these questions, the researchers will also have various instruments and materials (e.g. paper or computer tests, observation check lists etc.) and a clearly defined plan of action.

Data is collected by various means following a strict procedure and prepared for statistical analysis. Nowadays, this is carried out with the aid of sophisticated statistical computer packages. The analysis enables the researchers to determine to what extent there is a relationship between two or more variables. This could be a simple association (e.g. people who exercise on a daily basis have lower blood pressure) or a causal relationship (e.g. daily exercise actually leads to lower blood pressure). Statistical analysis permits researchers to discover complex causal relationships and to determine to what extent one variable influences another.

The results of statistical analyses are presented in journals in a standard way, the end result being a P value. For people who are not familiar with scientific research jargon, the discussion sections at the end of articles in peer reviewed journals usually describe the results of the study and explain the implications of the findings in straightforward terms

Principles

Objectivity is very important in quantitative research. Consequently, researchers take great care to avoid their own presence, behaviour or attitude affecting the results (e.g. by changing the situation being studied or causing participants to behave differently). They also critically examine their methods and conclusions for any possible bias.

Researchers go to great lengths to ensure that they are really measuring what they claim to be measuring. For example, if the study is about whether background music has a positive impact on restlessness in residents in a nursing home, the researchers must be clear about what kind of music to include, the volume of the music, what they mean by restlessness, how to measure restlessness and what is considered a positive impact. This must all be considered, prepared and controlled in advance.

External factors, which might affect the results, must also be controlled for. In the above example, it would be important to make sure that the introduction of the music was not accompanied by other changes (e.g. the person who brings the CD player chatting with the residents after the music session) as it might be the other factor which produces the results (i.e. the social contact and not the music). Some possible contributing factors cannot always be ruled out but should be acknowledged by the researchers.

The main emphasis of quantitative research is on deductive reasoning which tends to move from the general to the specific. This is sometimes referred to as a top down approach. The validity of conclusions is shown to be dependent on one or more premises (prior statements, findings or conditions) being valid. Aristotle’s famous example of deductive reasoning was: All men are mortal, Socrates is a man, Socrates is mortal. If the premises of an argument are inaccurate, then the argument is inaccurate. This type of reasoning is often also associated with the fictitious character Sherlock Holmes. However, most studies also include an element of inductive reasoning at some stage of the research (see section on qualitative research for more details).

Researchers rarely have access to all the members of a particular group (e.g. all people with dementia, carers or healthcare professionals). However, they are usually interested in being able to make inferences from their study about these larger groups. For this reason, it is important that the people involved in the study are a representative sample of the wider population/group. However, the extent to which generalizations are possible depends to a certain extent on the number of people involved in the study, how they were selected and whether they are representative of the wider group. For example, generalizations about psychiatrists should be based on a study involving psychiatrists and not one based on psychology students. In most cases, random samples are preferred (so that each potential participant has an equal chance of participating) but sometimes researchers might want to ensure that they include a certain number of people with specific characteristics and this would not be possible using random sampling methods. Generalizability of the results is not limited to groups of people but also to situations. It is presumed that the results of a laboratory experiment reflect the real life situation which the study seeks to clarify.

When looking at results, the P value is important. P stands for probability. It measures the likelihood that a particular finding or observed difference is due to chance. The P value is between 0 and 1. The closer the result is to 0, the less likely it is that the observed difference is due to chance. The closer the result is to 1, the greater the likelihood that the finding is due to chance (random variation) and that there is no difference between the groups/variables.

Qualitative research

Qualitative research is the approach usually associated with the social constructivist paradigm which emphasises the socially constructed nature of reality. It is about recording, analysing and attempting to uncover the deeper meaning and significance of human behaviour and experience, including contradictory beliefs, behaviours and emotions. Researchers are interested in gaining a rich and complex understanding of people’s experience and not in obtaining information which can be generalized to other larger groups.

The process

The approach adopted by qualitative researchers tends to be inductive which means that they develop a theory or look for a pattern of meaning on the basis of the data that they have collected. This involves a move from the specific to the general and is sometimes called a bottom-up approach. However, most research projects also involve a certain degree of deductive reasoning (see section on quantitative research for more details).

Qualitative researchers clearly identify a problem or topic that they want to explore and have clear research questions. They may also be guided by a theoretical lens - a kind of overarching theory which provides a framework for their investigation.

The approach to data collection and analysis is methodical but allows for greater flexibility than in quantitative research. Data is collected in textual form on the basis of observation and interaction with the participants e.g. through participant observation, in-depth interviews and focus groups. It is not converted into numerical form and is not statistically analysed, although many researchers now use computer programmes for qualitative data analysis (e.g. NVivo or Atlas.ti.) which help organize/manage large quantities of qualitative data.

Data collection may be carried out in several stages rather than once and for all. The researchers may even adapt the process mid-way, deciding to address additional issues or dropping questions which are not appropriate on the basis of what they learn during the process. In some cases, the researchers will interview or observe a set number of people. In other cases, the process of data collection and analysis may continue until the researchers find that no new issues are emerging.

Principles

Researchers will tend to use methods which give participants a certain degree of freedom and permit spontaneity rather than forcing them to select from a set of pre-determined responses (of which none might be appropriate or accurately describe the participant’s thoughts, feelings, attitudes or behaviour) and to try to create the right atmosphere to enable people to express themselves. This may mean adopting a less formal and less rigid approach than that used in quantitative research.

It is believed that people are constantly trying to attribute meaning to their experience. Therefore, it would make no sense to limit the study to the researcher’s view or understanding of the situation and expect to learn something new about the experience of the participants. Consequently, the methods used may be more open-ended, less narrow and more exploratory (particularly when very little is known about a particular subject). The researchers are free to go beyond the initial response that the participant gives and to ask why, how, in what way etc. In this way, subsequent questions can be tailored to the responses just given.

Qualitative research often involves a smaller number of participants. This may be because the methods used such as in-depth interviews are time and labour intensive but also because a large number of people are not needed for the purposes of statistical analysis or to make generalizations from the results.

The smaller number of people typically involved in qualitative research studies and the greater degree of flexibility does not make the study in any way “less scientific” than a typical quantitative study involving more participants and carried out in a much more rigid manner. The objectives of the two types of research and their underlying philosophical assumptions are simply different. However, as discussed in the section on “philosophies guiding research”, this does not mean that the two approaches cannot be used in the same study.

Pragmatic approach to research (mixed methods)

The pragmatic approach to science involves using the method which appears best suited to the research problem and not getting caught up in philosophical debates about which is the best approach. Pragmatic researchers therefore grant themselves the freedom to use any of the methods, techniques and procedures typically associated with quantitative or qualitative research. They recognise that every method has its limitations and that the different approaches can be complementary.

They may also use different techniques at the same time or one after the other. For example, they might start with face-to-face interviews with several people or have a focus group and then use the findings to construct a questionnaire to measure attitudes in a large scale sample with the aim of carrying out statistical analysis.

Depending on which measures have been used, the data collected is analysed in the appropriate manner. However, it is sometimes possible to transform qualitative data into quantitative data and vice versa although transforming quantitative data into qualitative data is not very common.

Being able to mix different approaches has the advantages of enabling triangulation. Triangulation is a common feature of mixed methods studies. It involves, for example:

• the use of a variety of data sources (data triangulation)
• the use of several different researchers (investigator triangulation)
• the use of multiple perspectives to interpret the results (theory triangulation)
• the use of multiple methods to study a research problem (methodological triangulation)

In some studies, qualitative and quantitative methods are used simultaneously. In others, first one approach is used and then the next, with the second part of the study perhaps expanding on the results of the first. For example, a qualitative study involving in-depth interviews or focus group discussions might serve to obtain information which will then be used to contribute towards the development of an experimental measure or attitude scale, the results of which will be analysed statistically.

Research methods

Experiments

People who take part in research involving experiments might be asked to complete various tests to measure their cognitive abilities (e.g. word recall, attention, concentration, reasoning ability etc.) usually verbally, on paper or by computer. The results of different groups are then compared. Participants should not be anxious about performing well but simply do their best. The aim of these tests is not to judge people or measure so-called intelligence, but to look for links between performance and other factors. If computers are used, this has to be done in such a way that no previous knowledge of computers is necessary. So people should not be put off by this either.

The study might include an intervention such as a training programme, some kind of social activity, the introduction of a change in the person’s living environment (e.g. different lighting, background noise, different care routine) or different forms of interaction (e.g. linked to physical contact, conversation, eye contact, interaction time etc.). Often the interaction will be followed by some kind of test (as mentioned above), sometimes before and after the intervention. In other cases, the person may be asked to complete a questionnaire (e.g. about his/her feelings, level of satisfaction or general well-being).

Some studies are just based on one group (within-group design). The researchers might be interested in observing people’s reactions or behaviour before and after a certain intervention (e.g. a training programme). However, in most cases, there are at least two groups (a between-subjects design). One of the groups serves as a control group and is not exposed to the intervention. This is quite similar to the procedure in clinical trials whereby one group does not receive the experimental drug. This enables researchers to compare the two groups and determine the impact of the intervention. Alternatively, the two groups might differ in some important way (e.g. gender, severity of dementia, living at home or in residential care, etc.) and it is that difference that is of interest to the researchers.

Surveys

Surveys involve collecting information, usually from fairly large groups of people, by means of questionnaires but other techniques such as interviews or telephoning may also be used. There are different types of survey. The most straightforward type (the “one shot survey”) is administered to a sample of people at a set point in time. Another type is the “before and after survey” which people complete before a major event or experience and then again afterwards.

Questionnaires

Questionnaires are a good way to obtain information from a large number of people and/or people who may not have the time to attend an interview or take part in experiments. They usually enable people to take their time, think about it and come back to the questionnaire later. With self-completed questionnaires, participants can state their views or feelings privately without worrying about the possible reaction of the researcher. Unfortunately, some people may still be inclined to try to give socially acceptable answers. People should be encouraged to answer the questions as honestly as possible so as to avoid the researchers drawing false conclusions from their study.

Questionnaires typically contain multiple choice questions, attitude scales, closed questions and open-ended questions. The drawback for researchers is that they usually have fairly low response rates and people do not always answer all the questions and/or do not answer them correctly. As they are usually anonymous, it is impossible to follow up and obtain the necessary information or clarity. Questionnaires can be administered in a number of different ways (e.g. sent by post or as email attachments, posted on Internet sites, handed out personally or administered to captive audiences (such as people attending conferences). Researchers may even decide to administer the questionnaire in person which has the advantage of including people who have difficulties reading and writing, and would not otherwise be able to take part in the study (especially people from marginalized groups). Participants might, however, be less honest when giving their responses to someone else. Questionnaires administered by Internet may have the advantages of reaching more people but may exclude certain groups of people.

Interviews

Interviews are usually carried out in person i.e. face-to-face but can also be administered by telephone or virtually (e.g. by Skype or zoom). Sometimes they are held in the interviewee’s home, sometimes at a more neutral place. It is important for interviewees to decide whether they are comfortable about inviting the researcher into their home and whether they have a room or area where they can speak freely without disturbing other members of the household. It is also important that researchers feel safe going into the homes of people they do not know.

The interviewer (which is not necessarily the researcher) could adopt a formal or informal approach, either letting the interviewee speak freely about a particular issue or asking specific pre-determined questions. This will have been decided in advance and depend on the approach used by the researchers. A semi-structured approach would enable the interviewee to speak relatively freely, at the same time allowing the researcher to ensure that certain issues were covered.

When conducting the interview, the researcher might have a check list or a form to record answers. This might even take the form of a questionnaire. Taking notes can interfere with the flow of the conversation, particularly in less structured interviews. Also, it is difficult to pay attention to the non-verbal aspects of communication and to remember everything that was said and the way it was said. Consequently, it can be helpful for the researchers to have some kind of additional record of the interview such as an audio or video recording. They should of course obtain permission before recording an interview.

Kvale and Brinkmann (2009) describe different philosophical approaches to qualitative interviewing, through the metaphors of the miner and the traveller. The miner metaphor describes knowledge as being like a buried valuable metal which the miner unearths without contaminating it in any way. It is there, intact, waiting to be discovered. The traveller metaphor describes knowledge as something that is constructed as a result of the traveller walking along with people, listening to their experience of the world, trying to make sense of it and retelling it on his or her return. This difference is also a reflection of different research paradigms.

Case studies

Case studies usually involve the detailed study of a particular case (a person or small group). Various methods of data collection and analysis are used but this typically includes observation and interviews and may involve consulting other people and personal or public records. The researchers may be interested in a particular phenomenon (e.g. coping with a diagnosis or a move into residential care) and select one or more individuals in the respective situation on whom to base their case study/studies. Case studies have a very narrow focus which results in detailed descriptive data which is unique to the case(s) studied. Nevertheless, it can be useful in clinical settings and may even challenge existing theories and practices in other domains.

Participant and non-participant observation

Studies which involve observing people can be divided into two main categories, namely participant observation and non-participant observation.

In participant observation studies, the researcher becomes (or is already) part of the group to be observed. This involves fitting in, gaining the trust of members of the group and at the same time remaining sufficiently detached as to be able to carry out the observation. The observations made might be based on what people do, the explanations they give for what they do, the roles they have, relationships amongst them and features of the situation in which they find themselves. The researcher should be open about what s/he is doing, give the participants in the study the chance see the results and comment on them, and take their comments seriously.

In non-participant observation studies, the researcher is not part of the group being studied. The researcher decides in advance precisely what kind of behaviour is relevant to the study and can be realistically and ethically observed. The observation can be carried out in a few different ways. For example, it could be continuous over a set period of time (e.g. one hour) or regularly for shorter periods of time (for 60 seconds every so often) or on a random basis. Observation does not only include noting what happened or was said but also the fact that a specific behaviour did not occur at the time of observation.

Observational trials

Observational trials study health issues in large groups of people but in natural settings. Longitudinal approaches examine the behaviour of a group of people over a fairly lengthy period of time e.g. monitoring cognitive decline from mid to late life paying specific attention to diet and lifestyle factors. In some cases, the researchers might monitor people when they are middle-aged and then again after 15 years and so on. The aim of such studies is usually to determine whether there is a link between one factor and another (e.g. whether high alcohol consumption is correlated with dementia). The group of people involved in this kind of study is known as a cohort and they share a certain characteristic or experience within a defined period. Within the cohort, there may be subgroups (e.g. people who drink moderately, people who drink heavily, people who binge drink etc.) which allow for further comparisons to be made.

In some cases, rather than following a group of people from a specific point in time onwards, the researchers take a retrospective approach, working backwards as it were. They might ask participants to tell them about their past behaviour, diet or lifestyle (e.g. their alcohol consumption, how much exercise they did, whether they smoked etc.) They might also ask for permission to consult the participants’ medical records (a chart review). This is not always a reliable method and may be problematic as some people may forget, exaggerate or idealise their behaviour. For this reason, a prospective study is generally preferred if feasible although a retrospective pilot study preceding a prospective study may be helpful in focusing the study question and clarifying the hypothesis and feasibility of the latter (Hess, 2004).

Studies using the Delphi method

The Delphi method was developed in the United States in the 1950s and 1960s in the military domain. It has been considered particularly useful in helping researchers determine the range of opinions which exist on a particular subject, in investigating issues of policy or clinical relevance and in trying to come to a consensus on controversial issues. The objectives can be roughly divided into those which aim to measure diversity and those which aim to reach consensus.

Different ways to employ this method have been devised but they tend to share common features, namely a series of “rounds” in which the participants (known as “panelists”) generate ideas or identify salient issues, comment on a questionnaire (constructed on the basis of the results from the first round) and re-evaluate their original responses. After each round, a facilitator provides an anonymous summary of the forecasts/opinions made by the experts and of their reasons.

There is no limit to the number of panelists involved but between 10 and 50 might be considered manageable. The panelists are chosen on the basis of their expertise which could take many forms (e.g. academic, professional or practical knowledge, personal experience of having a condition, being a service user etc.).

Clinical trials

What is a clinical trial?

A clinical trial is a biomedical/health-related research study into the effects on humans of a new medical treatment (medicine/drug, medical device, vaccine or new therapy), sometimes called an investigational medicinal product (IMP). Before a new drug is authorised and can be marketed, it must pass through several phases of development including trial phases in which its safety, efficacy, risks, optimal use and/or benefits are tested on human beings. Existing drugs must also undergo clinical testing before they can be used to treat other conditions than that for which they were originally intended.

European requirements for clinical trials

Organisations conducting clinical trials in the European Union must, if they wish to obtain marketing authorisation, respect the requirements for the conduct of clinical trials which can be found in the Clinical Trials Regulation (Regulation (EU) No 536/2014). This Clinical Trials Regulation came into application on 31 January 2022 and replaced the past EU Clinical Trials Directive 2001/20/EC and national legislation that was put in place to implement the Directive.

Under the Clinical Trials Regulation, all clinical trial applications for trials with medicinal products in humans have to apply through a Clinical Trial Information System (CTIS). CTIS is a single-entry point for sponsors and regulators of clinical trials for the submission and assessment of clinical trial. This is done to harmonise and streamline the processes for application and supervision of clinical trials throughout the EU. With CTIS, sponsors can apply for authorisations in up to 30 EU/EEA countries at the same time and with the same documentation.

The European Medicines Agency (EMA) sets up and maintains CTIS, in collaboration with the Member States and the European Commission. Information stored in CTIS are publicly available for transparency.

The Clinical Trials Regulation (Regulation (EU) No 536/2014) foresees a three-year transition period. From 31 January 2022, clinical trial sponsors can choose whether to submit an initial clinical trial application in line with the past system (Clinical Trials Directive 2001/20/EC) or via CTIS. From 31 January 2023, submission of initial clinical trial applications via CTIS becomes mandatory. It will also apply to trials authorised under the previous legislation if they are still ongoing on 31 January 2025, they will have to be transitioned to CTIS.

The European Medicines Agency (EMA) plays a key role in ensuring the standards of good clinical practice (GCP) are applied across the European Union. Guidelines to ensure that clinical trials are carried out in accordance with good clinical practice are contained in the “Commission Directive 2005/28/EC of 8 April 2005 laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing or importation of such products” (also known as the Good Clinical Practice or GCP for short). This document provides more concrete guidelines and lends further support to the Clinical Trials Directive. In addition, EMA has published further guidance on clinical trial management during the COVID-19 pandemic. This covers how to deal with the extraordinary situations that the pandemic presents and specific advice on clinical trials for potential COVID-19 treatments.

EMA has also published additional, more specific guidelines which must also be respected. These include guidelines on inspection procedures and requirements related to quality, safety and efficacy.

Copies of the above-mentioned documents and the new Directive applicable on 31 January 2022 (available in 24 EU languages) can be found at: https://www.ema.europa.eu/en/human-regulatory/research-development/clinical-trials-human-medicines

Types of clinical trials

Clinical trials can be categorised according to their objectives and also the way they are organised. For example, they might be prevention trials, treatment/drug trials or diagnostic and screening trials.

• Interventional trials (also called treatment trials or clinical drug trials) are clinical trials which set out to test treatments or combinations of treatments which have not yet been officially approved. For example, a pharmaceutical company may have developed a new drug which it believes would be effective in the treatment of Alzheimer’s disease but must first test it on human volunteers in accordance with strict and rigorous guidelines in order to ensure that it is safe and effective. Some drugs might be aimed at curing a particular condition, whereas others might be aimed at better controlling symptoms of a particular condition.
• Prevention trials involve tests to find ways to prevent particular medical conditions or if people have them already, to prevent them from reoccurring. The emphasis of these studies might be on medicines, vitamins and minerals or lifestyle changes.
• Observational trials investigate health issues in large groups of people. The participants in such trials do not receive any treatment but may be asked to provide information, blood samples.
• Diagnostic and screening trials are aimed at finding new ways to detect and diagnose medical conditions (e.g. a better test, a more effective procedure or a more sophisticated tool).

In addition, clinical trials may be described as randomised trials, blind trials, add-on studies, open label trials or randomised double-blind placebo-controlled trials. These terms provide information about the way that the trial is organised which may have consequences for the participants (mostly with regard to the inclusion of a placebo group which is fairly common. A brief description of some of these terms is provided below:

Phases of clinical trials

Testing an experimental drug or medical procedure is usually an extremely lengthy process, sometimes lasting several years. The overall procedure is divided into a series of stages (known as phases) which are described below.

Pre-clinical testing

Clinical testing on humans can only begin after a pre-clinical phase, involving laboratory studies (in vitro) and tests on animals, which has shown that the experimental drug is considered safe and effective. However, no animal is sufficiently similar to humans (even genetically modified ones) to make human testing unnecessary. For this reason, the experimental drug must also be tested on humans.

Whilst a certain amount of testing can be carried out by means of computer modelling and by isolating cells and tissue, it becomes necessary at some point in time to test the drug on a living creature. Animal testing is an obligatory stage in the process of obtaining regulatory approval for new drugs and medicines, and hence a legal requirement (EU Directive 2001/83/EC relating to Medicinal Products for Human Use). This applies to prescription and vaccine drugs but not to most over the counter drugs, off the shelf medicines and healthcare products (as the ingredients in them have usually already been tested). The necessity of carrying out prior testing on animals is also stated in the World Medical Association’s “Ethical Principles for Medical Research Involving Human Subjects.

In order to protect the well-being of research animals, researchers are guided by three principles which are called the 3Rs:

1. Reduce the number of animals used to a minimum
2. Refine the way that experiments are carried out so that the effect on the animal is minimised and animal welfare is improved
3. Replace animal experiments with alternative (non-animal) techniques wherever possible.

In addition, most countries will have official regulatory bodies which control animal research.

The main phases of clinical trials

Clinical trials on humans can be divided into three main phases (literally, phase I, II and III). Each phase has specific objectives (please see below) and the number of people involved increases as the trial progresses from one phase to the next. General speaking the overall aims of the three phases are:

1. Phase 1: determine safety
2. Phase 2: determine whether the drug works
3. Phase 3: determine how effective the drug is compared to currently available, effective drugs

Phase I trials

Phase 1 trials are usually the first step in testing a new drug or treatment on humans after successful laboratory and animal testing. They are usually quite small scale and usually involve healthy participants or sub-groups of participants who share a particular characteristic. The aims of these trials are:

• to assess the safety of experimental drugs
• to evaluate any possible side effects
• to determine a safe dose range
• to see how the body reacts to the drug (how it is absorbed, distributed and eliminated from the body, and the effects that it has on the body).

Dose ranging, sometimes called dose escalation, studies may be used as a means to determine the most appropriate dosage, but the doses administered to the participants should only be a fraction of those which were found to cause harm to animals in the pre-clinical studies.

The process of determining an optimal dose in phase I involves quite a high degree of risk because this is the first time that the experimental treatment or drug has been administered to humans. Moreover, healthy people’s reactions to drugs may be different to those of the target group. For this reason, drugs which are considered to have a potentially high toxicity are usually tested on people from the target group.

There are a few different approaches to phase I trials e.g. single ascending dose studies, multiple ascending dose studies and food effect.

In single ascending dose studies (SAD), a small group of participants receive a small dose of the experimental drug and are then observed in order to see whether that dose results in side effects. For this reason, trials are usually conducted on an inpatient basis. If no adverse side effects are observed, a second group of participants are given a slightly higher dose of the same drug and also monitored for side-effects. This process is repeated until a dose is reached which results in intolerable side effects. This is defined as the maximum tolerated dose (MTD).

Multiple ascending dose studies (MAD) are designed to test the pharmacokinetics and pharmacodynamics of multiple doses of the experimental drug. A group of participants receives multiple doses of the drug, starting at the lowest dose and working up to a pre-determined level. At various times during the period of administration of the drug, and particularly whenever the dose is increased, samples of blood and other bodily fluids are taken. These samples are analysed in order to determine how the drug is processed within the body and how well it is tolerated by the body.

Food effect studies are investigations into the effect of food intake on the absorption of the drug into the body. This involves two groups of participants being given the same dose of the experimental drug but for one of the groups when fasting and for the other after a meal. This allows researchers to see whether eating before the drug is given has any effect on the absorption of the drug by the body.

Phase II trials

Having demonstrated the initial safety of the drug (often on a relatively small sample of healthy individuals), phase II clinical trials can begin. Phase II studies are designed to explore the therapeutic efficacy of a treatment or drug in people who have the condition that the drug is intended to treat. They are sometimes called therapeutic exploratory trials and tend to be larger scale than Phase I trials. Many experimental drugs which fail tend to do so during the Phase II trials.

Phase II trials can be divided into Phase IIA and Phase IIB although sometimes both are combined.

• Phase IIA is designed to assess dosing requirements i.e. how much of the drug should patients receive and up to what does is considered safe. The safety assessments carried out in Phase I can be repeated on a larger subject group. As more participants are involved, some may experience side effects which none of the participants in the Phase I experienced. The researchers aim to find out more about safety, side effects and how to manage them.
• Phase IIB studies focus on the efficacy of the drug i.e. how well it works at the prescribed doses. Researchers may also be interested in finding out which types of a specific disease or condition would be most suitable for treatment.

Phase II trials can be randomized clinical trials which involve one group of participants being given the experimental drug and others receiving a placebo (dummy pill). Alternatively, they may be case series which means that the drug is safety and efficacy is tested in a selected group of patients. If the researchers have adequately demonstrated that the experimental drug (or device) is effective against the condition for which it is being tested, they can proceed to Phase III.

Phase III trials

Phase III trials are the last stage before clinical approval for a new drug or device. By this stage, there will be convincing evidence of the safety of the drug or device and its efficacy in treating people who have the condition for which it was developed. Such studies are carried out on a much larger scale than for the two previous phases and are often multinational. Several years may have passed since the original laboratory and animal testing.

The main aims of Phase III trials are:

• to demonstrate that the treatment or drug is safe and effective for use in patients in the target group (i.e. in people for whom it is intended)
• to monitor side effects
• to test different doses or different ways of administering the drug
• to determine whether the drug could be used at different stages of the disease.
• to provide sufficient information as a basis for marketing approval

Researchers may also be interested in showing that the experimental drug works for additional groups of people with conditions other than that for which the drug was initially developed. For example, they may be interested in testing a drug for inflammation on people with Alzheimer’s disease. The drug would have already have proven safe and obtained marketing approval but for a different condition, hence the need for additional clinical testing.

Post-marketing surveillance studies (phase IV)

After the three phases of clinical testing and after the treatment has been approved for marketing, there may be a fourth phase to study the long-term effects of drugs or treatment or to study the impact of another factor in combination with the treatment (e.g. whether a particular drug reduces agitation).

Usually, such trials are sponsored by pharmaceutical companies and described as pharmacovigilance. They are not as common as the other types of trials (as they are not necessary for marketing permission). However, in some cases, the European Medicines Evaluation Agency (EMEA) grants restricted or provisional marketing authorisation, which is dependent on additional phase IV trails being conducted.

Expanded access to a trial

Sometimes, a person might be likely to benefit from a drug which is at various stages of testing but does not fulfil the conditions necessary for participation in the trial (e.g. s/he may have other health problems). In such cases and if the person has a life-threatening or serious condition for which there is no effective treatment, s/he may benefit from “expanded access” use of the drug. There must, however, be evidence that the drug under investigation has some likelihood of being effective for that patient and that taking it would not constitute an unreasonable risk.