What Is Clinical Research

Clinical research is scientific study that involves people. Individuals volunteer to

participate in carefully conducted studies which ultimately uncover improved

methods and knowledge on screening, diagnoses, treatment and prevention of

disease and on the promotion of health and health care.

Clinical research can be interventional or observational. Observational studies are projects where there is no investigational product assigned to participants, e.g. research on how therapies work, health economic research and qualitative clinical research such as understanding patients’ experiences, etc.Interventional studies are controlled experiments, like clinical trials, where every participant is allocated to the treatment or control group at the start of the study. The WHO’s International Clinical Trials Registry Platform states that ‘interventions can include drugs, cells and other biological products, surgical procedures, radiologic procedures, devices, behavioural treatments,process-of-care changes, preventive care, etc ’.

Studies can be run in just one location and are referred to as ‘single centre studies’, or they can be run across many sites, and these are called ‘multi-centre studies’. Whether a study is single or multi-centred will depend upon the type and scale of the research being undertaken.

How Does Clinical Research Differ From Standard Care?

The difference between clinical research and standard care is that clinical research:

involves human volunteers, these may be patients or can all be healthy individuals who are not

suffering from an illness or condition.is carried out with the ultimate aim of improving standard care. The research may be testing an intervention (e.g. a product or procedure) or collecting data through interviews or observations about a topic such as patient experience, disease management etc.measures effects over a period of time using robust and reliable methods to identify a lack of knowledge on issues such as costs, improved care, better drugs, treatments or therapies,additional support etc.may involve a comparison ‘control’ group, depending on the type of research.

focuses on unknowns such as the effect of intervention, the likelihood of a community to

change their practices, etc.must stick to a protocol without deviation (within the investigator’s clinical judgement). By comparison standard care is all about clinical judgment, decisions and flexibility.

Why Do We Perform Clinical Research?

Clinical research is undertaken to collect data on usual and unusual events, conditions, and

population groups to allow us to:

observe treatment and health management practices so that we learn how they can be improved upon

test interventions to develop new drugs and vaccines and to find new usesfor existing therapies

learn more about specific diseases so we can better understand how to manage, treat and prevent them

Ultimately the aim is to better understand how, with clinical research, we can improve health

outcomes.During the 20th century the huge improvements seen in global health were mainly a result of the knowledge gained through clinical research, examples include:

1920s: research found that improving childrens’ nutrition helped combat rickets and other

childhood diseases.

1950s: epidemiological research proved that cigarette smoking caused lung cancer.

1980s: trials proved that giving folic acid to high-risk women resulted in a reduction of babies

born with spina bifida.

1990s: clinical trials showed that the progress of AIDS could be delayed by combining antiretroviral drugs.

Why Do We Perform Clinical Research?

Areas of highest disease burden, such as low-income countries, stand to gain the most from

clinical research as there is the greatest potential for improving health in numerical terms, and

there is enormous possible gain from relatively simple interventions. However, these populations are currently under-represented in research activities worldwide.Current and future research efforts will hopefully bring more effective treatments and vaccines for diseases like malaria, HIV, tuberculosis, and neglected diseases such as dengue, visceral leishmaniasis, etc. These efforts should also allow us to improve both our understanding of the health care needs of different individuals, groups and populations, and the health care provisions required to meet these needs.

The most reliable way of improving health outcomes is through continuous, rigorous, credible and varied clinical research that involves different people and communities.Introduction: Key Points To Remember Clinical research investigates questions about human disease, diagnosis, prevention,outcomes and treatments and about promoting health and health care.Clinical research can be observational (e.g. health economic research) or interventional (e.g. clinical trials).Improving standard care is one of the aims of clinical research.Clinical research has resulted in huge improvements in global health in the 20th century.Though currently under represented in world-wide research activities, areas of highest disease burden, such as low-income countries stand to gain the most from clinical research.

What Are The Main Principles Of Research Ethics ?

The Belmont report lists three basic principles which are particularly relevant to the ethics of research that involves human participants.These three principles are as follows:

Justice: no group should carry more than their fair share of the burdens of research, those who participated should have access to the benefits of the results and no group should be unfairly excluded from research. In their paper, Minnies et al. (2008) emphasise that ‘poverty,disease, lack of education, hardship, submissiveness, the effects of war, famine, pandemics,and social insecurity prevalent in developing countries all make participants more vulnerable to research exploitation’.

Beneficence: possible harms should be minimised and possible benefits should be maximised.

Respect for autonomy: individuals’ freedom to choose and act must be respected and vulnerable individuals must be protected.The Council for International Organisations of Medical Sciences (CIOMS) 2002 ‘International Ethical Guidelines for Biomedical Research Involving Human Subjects’ list an additional principle:Non-maleficence: participation in the study should result in no intentional injury or harm for the individual.

What Are The Main Principles Of Research Ethics ?

Research governance is the broad range of regulations, principles and standards of good practice that are in place to ensure participants are protected and quality is assured across all aspects of clinical research. It is a mechanism for ensuring that all human research complies with the relevant ethical and legal standards.

However as the CIOMS guidelines state:

‘The challenge to international research ethics is to apply universal ethical principles to biomedical research in a multicultural world with a multiplicity of health-care systems and considerable variation in standards of health care. Research involving human subjects must not violate any universally applicable ethical standards, but the guidelines acknowledge that, in superficial aspects, the application of the ethical principles, e.g. in relation to individual autonomy and informed consent, needs to take account of cultural values, while respecting absolutely the ethical standards.’

What Is Informed Consent And Why Is It Needed?

The main mechanism for ensuring an individual’s rights are protected is ‘Informed Consent’.

The process of informed consent involves explaining to the potential participant about all of the study-related activities that are beyond standard care and to ask for that person’s consent to be included in the study.Following famous cases such as the Nazi’s experiments on concentration camp prisoners in WWII and the Tuskegee syphilis study (1932 –1972) on black American men, agreements for the conduct of clinical research were created. These agreements included the 1947 Nuremberg code,the 1964 Declaration of Helsinki and the 1979 Belmont Report, and led to the development of the International Conference on Harmonization Principles of Good Clinical Practice (ICH GCP) 1996guidelines . Though the ICH-GCP guidelines are for trials, most of the principles can be applied to any type of study. These guidelines define informed consent as:

‘the process by which a person freely confirms their willingness to participate in clinical research after having been informed of all parts of the study that are relevant to the individual’s decision to participate’.

What Is Informed Consent And Why Is It Needed ?
The challenges and issues around gaining fully informed consent are one of the most highly discussed and important elements, particularly from an ethics perspective, in the conduct of clinical research. In their paper, Mystakidou et al. (2009) emphasise that the process of obtaining consent should be an on-going process, and that it is not a single event (i.e. reading and signing a form) and is not just based on the information and the form. There should be a wider consideration of what information should be conveyed, when and by whom. This will lead to the development of a study-specific consent process, including a training plan and operating procedures, which can be just as important as the consent form itself.
When thinking through an appropriate consent process you might wish to consider factors such
as the benefits or risks for the individuals or groups (e.g do benefits outweigh risks), the length
and level of participation required, the vulnerability of the proposed study population e.g.impoverished, low education level, children) and the perception of the community (e.g will approval of the research activity from community leaders be required before the individual members of the community consider being involved).
What Is Informed Consent And Why Is It Needed ?
When taking consent from a participant, the investigator should:
1. fully inform the potential participant of all applicable parts of the study such as its purpose,
duration, required procedures, and key contacts
2. be sensitive to the needs of individuals who are part of vulnerable groups e.g. children,
someone from a poor background who won’t normally have access to medical care, someone
with very little or no schooling, someone who has limited mental capacity to understand, etc.
3. explain the benefits and risks involved in taking part
4. encourage questions and give reassurance that, if the person agrees to participate, they can
always ask the research team for additional information throughout the study
5. ensure that the participant understands that if they change their mind about participation they
can leave the study and are under no obligation to explain why they are leaving
6. be able to communicate using simple, non-technical wording in a language the person can
understand (or have an independent person who can)
7. treat the potential recruit with up most respect even if they decline to participate
What Is Informed Consent And Why Is It Needed (d)?
Informed consent should be documented by means of a written, signed and dated informed
consent form. In some cases the volunteer may be unable to sign for themselves, e.g. young
children, the very old or even someone with an injury to their hand. In these cases someone who is independent from the study should sign as a witness that the individual agreed to participate. No study procedures are allowed to take place before the informed consent process is complete and the informed consent document is signed.
It is essential that the participant understands that the informed consent form is not a contract.
Different kinds of clinical research require different types of information sheets and consent forms,specific to each study, to be designed. Care should be taken in designing consent forms as a common error in consent forms is mixing research-only processes and standard care
procedures. This can risk those who decline to participate being opted out of a procedure they
should receive regardless of the research.Examples of some consent forms can be found through the link provided in the ‘References and Resources’ section of this module.
What Is Informed Consent and Why Is It Needed ?
However it should be noted that there are certain populations where signing a form is not
considered appropriate e.g. communities and populations that are illiterate. Creed-Kanashiro et al.(2005) cite examples of nutritional studies run in the highlands of Peru where “the rural community were suspicious of signing a document they were unable to read because they had lost land by signing a document”. In these cases the ethics committee felt signed forms were unsuitable and consent was based first on approval of the project by the community leaders and then on the verbal consent of the individuals.The 2002 CIOMS guidelines state that
“Informed consent should be obtained according to the legal requirements and cultural standards of the community in which the intervention is carried out.”It is very common for communities in low-income countries to have high levels of illiteracy.
In such situations the participant cannot read the information sheet themselves and a
signature is not possible. In these cases an impartial witness is involved. This witness
signs the consent form to confirm that they have observed the participant (or where
appropriate the parent or guardian of the participant) has had the information sheet read
out to them in full and that they have understood the information and have had all of their
questions answered. The witness signs and the participant (or their parent/legal guardian) then
provides their thumbprint, with the person taking consent writing their name and the date. Other methods used for non-paper based societies include taking an audio or video recording of the consent process.Why Do People Participate In Clinical Research And What Are The
Benefits And Risks Involved (a)?The majority of clinical research studies offer no potential benefit for the participant.The person is simply involved in activities such as supplying samples, agreeing to undergo tests, providing information through questionnaires and interviews, or agreeing to be observed. Therefore most people participate in scientific research hoping that it will benefit future patients rather than for personal gain.
However, even when providing samples, information or undergoing tests there can be ‘risks’
involved. These risks can include things like: being asked highly sensitive questions, sharing
genetic data, undergoing diagnostic tests, having to take time off from work to participate, etc.
Sometimes inconvenient amounts of travel, or travel over long distances, may be required as
clinical research can be run in varied locations such as hospitals, doctors’ offices, community
clinics, universities and schools.Why Do People Participate In Clinical Research And What Are The Benefits And Risks Involved (b)?In the case of interventional clinical trials some participants may volunteer in the hope that the drug/treatment/therapy being tested is better than their existing regime. However it is important to explicitly explain to potential recruits that
new does not necessarily mean better and that they may actually receive a placebo (where one is being used) . Participation may even require that the individual stops using their current drug,treatment or therapy.Other risks of participation can include: side effects which could vary from mild to life-threatening and may or may not resolve, additional tests, more trips to the study site than the person would normally make to their doctor, extra doses/sessions of the experimental drug/therapy/treatment,etc.The members of the research team responsible for recruitment must be careful to emphasis that the purpose of the study is to find an answer to a specific scientific question and not to offer individualized or specialist medical care.
The processes for consenting individuals to the study and the procedures for continued
communication and follow up e.g. letters, newsletters, etc., should be outlined in the protocol.
Research Ethics: Key Points To Remember Non-maleficence, beneficence, respect for autonomy and justice are the main principles of research ethics.The application of ethical principles should take account of cultural values, while respecting the ethical standards.
The purpose of informed consent is to explain about all of the study related activities and
to ask for that person’s consent to be included in the study. Informed consent is an ongoing
process throughout the study.The signed informed consent document (where one exists) is not a contract and is not in any way binding.The main reason people agree to participate in clinical research is for the potential benefit of future patients.There are risks involved in both observational and Internationale research and these caninclude: being asked sensitive questions, sharing genetic data, long or inconvenient amounts of travel and potentially