A Roadmap to Research

The first part of this series will give a brief overview of the research process and the steps needed to get from formulating the question to dissemination of the results.

Figure 1. Overview of the research process.

Identify and define the research question

As clinicians we are experts in caring for patients with vascular disease along with their other co-existing conditions.  We should strive to use the best evidence to inform our professional practice and aim to continually improve our patient care. 

However, there are many questions that we can generate from our practice, including “How can we do this better?”; “How good is our current practice?”; “Does it meet the standards set?”.  These questions broadly fit into 1) Research; 2) Service Evaluation; or 3) Clinical Audit.  It is important to decide what category your study or project fits into, as that will have implications on its design, data collection and governance. Link at https://www.hra-decisiontools.org.uk/research/ .

Literature Review

The next step in the research process is to determine what is already known and where the current gaps are in the knowledgebase. This can be carried out in an informal manner by a quick informal literature review, by searching keywords in a search engine, e.g., PubMed.

A formal Systematic Review follows a much more structured manner.  It is designed to be robust and reproducible to ensure the minimisation of bias from the literature review process.  The stages include: 1) Framing questions for a review; 2) Identifying relevant work; 3) Assessing the quality of studies; 4) Summarising the evidence; 5) Interpreting the findings.

When the literature review has been carried out and the papers, conference proceedings, etc. have been selected, then it is important to critically appraise the published research. 

• Does this study address a clearly focused question?
• Did the study use valid methods to address this question?
• Are the valid results of this study important?
• Are these valid, important results applicable to my patient or population?

Formulate the research question and hypothesis

After the literature review has been conducted it is time to formulate the research question and if appropriate a hypothesis.  These will define exactly what you intend to research about your topic. Without a strong research question, you should not expect to develop a strong research answer.  Research questions tend to be more open-ended, while hypotheses are more direct, focused and closed.

A research question is a concise and focused question that provides a clear base for the research.  It is more often used in exploratory studies, where the relationships between the variables are more uncertain.  It doesn’t make a statement on if relationships exist between the variables.  One way to construct a well-built question is to use the PICO model: Population; Intervention: Control; Outcome.  This enables the researcher to construct a question that is specific to the patient population concerned, to include the new intervention or diagnostic test and an appropriate comparator.  It is also important to carefully consider the most suitable outcome to be measured.

A hypothesis is a formal statement about the relationship between two or more variables.  It is most appropriate for experimental studies and when there is a large body of evidence that provides information of how the variables of concern interact. 

Study Design

There are many ways to carry out a research project as can be seen in Figure 2. 

Figure 2. Tree of different study designs.

The study design will be influenced by the research question including primary outcome variable chosen.  A descriptive study aims to describe what is happening in a population (e.g. the prevalence, incidence or experience of a group.  An analytic study attempts to quantify the relationship between two factors (an intervention or exposure and the outcome).  Experimental studies manipulate the intervention or exposure and compares to the outcome between the groups (parallel or crossover design).  In observational studies, the researcher measures the intervention or exposure that occurs normally and then records the outcome (cohort - over a period of time or cross-sectional – at one time point)

The sample size of a study is the number of observations or patients recruited to a study.  It is an important feature of any study in which the goal is to make inferences about a population from a sample.  It can be a balance between higher precision and narrow confidence intervals afforded by a large sample size and the minimum number of observations/recruits needed to be able to answer the research question.

It is important to get the sample size right as it’s unethical to recruit too many participants than needed.  It is also unethical to recruit too few and not be able to reach a properly powered conclusion, due to wide confidence intervals and the risk of errors in statistical hypothesis testing.

Samples size calculation usually requires the expertise of a statistician, as it involves assessing the data from the literature of previous pilot studies to calculate the exact number needed.  A sample size for a pilot or feasibility study can be much smaller and estimated from experience rather than calculated.

An important aspect of study design is to take account of the opinions of patients and public that have experience of the disease being studied.  Patient and Public Involvement (PPI) should be an integral part of the research as this group can offer new insights to the treatments or diagnostic regime being investigated.  It is obvious that patients are recruited as participants of a study, but they can act as reviewers, help protocol development and if appropriate be co-investigators.  PPI is also a requirement for ethical review and often for funding opportunities.

Funding

All research needs to be funded, as even at the most basic level there are costs associated with carrying out additional data collection and analysis.  These costs may be met by the host department, on an ad-hoc basis, as part of a clinical role or as part of STP training.  However, larger research studies or more exploratory studies require external funding due to their complex nature.  Funding is available from a variety of sources, such as Trust/Institutional funding calls, charities or professional bodies (including the SVT), NIHR, UK research councils.

The SVT offers Research Grants of up to £4000 per project to both ordinary members and special interest groups.  The Research/Innovation award is to enable Vascular Scientists to conduct small-scale studies such as pilot or feasibility studies, with the hope that larger grants will be applied for at a later date.  There is a total of £10,000 available per year, with a maximum of £4,000 per award.

For more information see https://www.svtgbi.org.uk/research/svt-grant-application or email Yvonne Sensier - grants@svtgbi.org.uk

Research Governance and Approvals

A study protocol is the plan or set of steps to be followed for the duration of the study.  It details the rationale for the study, the hypotheses, the outcome measures, the plan for participant identification and recruitment and the statistical analysis plan.  It also details the governance arrangements in place to ensure the study is safe.

Research governance can be defined as a broad range of regulations, principles and standards of good practice that exist to achieve and continuously improve research quality across all aspects of healthcare.  It is needed to safeguard participants, protect researchers, enhance ethical and scientific quality, minimise risk, monitor and promote good research practice.

Trust/Institutional Research and Development departments must be consulted early in the research process, to ensure the appropriate research governance agreements are in place before the research commences.  They will be able to advice on sponsorship and to carry out capacity, capability and risk assessments.  A sponsor is the organisation that takes on overall responsibility for proportionate, effective arrangements being in place to set up, run and report a research project. 

All research participants (with very limited exceptions) need to provide Informed consent to take part in research.  This must be carried out by a trained member of the research team and usually includes issuing a Patient Information Sheet (PIS).

To gain the appropriate approvals you will need to access the HRA website (hra.nhs.uk).  It is an NHS website and provides a wealth of information on the research planning and approvals that are needed to carry out a research project in the within the NHS.  The Integrated Research Application system (IRAS) is found at www.myresearchproject.org.uk.  Normally for a research study you would need approvals from the HRA, a Research Ethics Committee and your local Trust/Institution R&D department.  Depending on you research, you may also need MHRA approval or the Human Tissue Authority.

Good Clinical Practice (GCP) is the international ethical, scientific and practical standard to which all clinical research is conducted.  It is important that everyone involved in research is trained or appropriately experienced to perform the specific tasks they are being asked to undertake.  The NIHR offers GCP training at https://www.nihr.ac.uk/health-and-care-professionals/learning-and-support/ and it’s important to keep up to date by renewing every 2 years.

Data Capture and Analysis

When the study has been approved and the green light given it is time for patient recruitment.  Then the next stage of the research process is to collect the data stated in the protocol.  This is done at baseline and then every follow-up visit after that.

Data can be collected in a variety of ways, including specific research activities (demographics, clinical examination/measurements, scans, tests, questionnaires) or data can be collected from usual clinical activities.  Obviously, these will be study specific and must be justified.  Data can be collected by using case-report forms (CRFs) that are specifically designed for the research study being undertaken and can be paper or electronic.  It is then stored in a database or spreadsheet for data analysis.

It is very important to complete as many of the data points as possible, as missing data can hamper the data analysis and possibly render the results meaningless.  More complex study designs and increased patient visits, can lead to an increase in the chance of missing data.  Another consideration is how image data e.g. duplex scans, CT or MRIs will be anonymised, transferred and stored and this must be explained in the protocol and the ethics forms.

When all the data has been collected then data analysis can be carried out, which can include the analysis of the raw data or sample, such as image analysis or biochemical analysis.  The next step is statistical analysis, where the aim is to describe the study sample (descriptive stats – age, sex, BMI, etc.) and to test for differences between the groups (t-test, chi-squared test, etc.).  Depending on the study design it can also feature correlation and/or regression analysis as well as survival analysis, amongst others.  Basic statistics can be done by a trained researcher but more advanced methods (especially for larger studies) should be done by or under the supervision of a statistician.  It is important to follow the statistical plan that was set out in the protocol as any ad-hoc analysis can be underpowered, leading to significant errors and incorrect interpretation.

Dissemination

When the data has been analysed and interpreted is it important to disseminate this findings and limitations of the study to the public and professionals.  This is to ensure new findings are available in the literature and can be evaluated by relevant peer groups.  It also enables the implementation of research findings into practice (with the involvement of commissioners) or guidelines (such as NICE).  The format of the report will be different for each method.  However, it is essential to include the background, hypothesis/rationale, methods, results and discussion and conclusion.

Dissemination can involve presenting at local research or MDT meetings, submission to conferences (such as the SVT ASM) as posters or presentations and by publication in a peer-reviewed journal.

It is also important to inform research participants of research findings with a lay summary and/or a copy of the journal article.

Useful websites and information

nihr.ac.uk – which includes a glossary, details on the Research Design Service, a list of Funding opportunities, and several modules on Learning for research including GCP, PI and Informed Consent training.

hra.nhs.uk – is an NHS website and provides a wealth of information on the research planning and approvals that are needed to carry out a research project in the within the NHS.

Integrated Research Application system (IRAS) – is found at www.myresearchproject.org.uk

ct-toolkit.ac.uk – is a very detailed roadmap for the stages of the research process.  It is aimed at those undertaking drug trials (Clinical Trials of Investigational Medicinal Products - CTIMPs), but there is a wide range of information that is useful for everyone involved in research.

R&D Department - Your R&D department is a wealth of knowledge and expertise.  You should engage at with them very early on in the research process.

Good Scientific Practice (GCP) - All researchers need to have GCP training and training modules can be found at www.learn.nihr.ac.uk.

Chief Investigator (CI)/Principal Investigator (PI) - The chief investigator (CI) is the person who takes overall responsibility for the design, conduct and reporting of a study. The principal investigator is the person at each site who is responsible for the day to day running of the research project.  In a single site study they are the same person. 

Clinical Trial Units - Specialist units with a specific remit to design, conduct, analyse and publish clinical trials and other well-designed studies.

Clinical Trial Manager - the person who is responsible for the day to day running of a trial.

Clinical Research Practitioner - a patient facing member of the research delivery team.

National Institute of Health Research (NIHR) - a government agency which funds research into health and care and it is the largest national clinical research funder in Europe.  NHS Research Scotland and Health and Care Research Wales are the equivalent in Scotland and Wales respectively.

Clinical Research Network (CRN) - supports patients, the public and health and care organisations to participate in high-quality research. The CRN comprises 15 Local Clinical Research Networks across England.

Research Design Service (RDS) - provides support to health and social care researchers on all aspects of the research process in England. 

Research Ethics Committee (REC) – these committees exist to protect the rights, safety, dignity and well-being of research participants and to facilitate and promote ethical research that is of potential benefit to participants, science and society.  They are made up of groups of volunteer members (lay and specialist) that review studies and provide ethical advice and approvals.