• Introduction
• How does it work?
• Fair tests
• How is it performed?
• Results
• Safety
• Selected links
• Useful Article?

Introduction

Research and clinical trials are an everyday part of the work done in the NHS.

The people who carry out research are mostly the same doctors and healthcare professionals who treat people. Their aim is to find better ways of looking after patients and keeping people healthy.

There are many different types of research and they cover a range of activities, from working in a scientific laboratory to carefully noting patterns of health and disease and developing new treatments.

Health and social care research looks at many different issues, from illness, disease and disability to the way that health and social care services are provided by the NHS.

Why carry out research?

People being cared for in the NHS benefit from past research and continue to benefit from research that is currently being carried out.

Healthcare professionals know a great deal about health, disease and medicines, but much remains uncertain. Research can find answers to the things that are unknown, filling gaps in knowledge and changing the way that healthcare professionals work. This means treatment, care and patients' quality of life are improved and avoidable early deaths are prevented.

Where is research carried out?

There is a huge range of different types of research into health and disease. Much research is carried out in the NHS, but some takes place in universities and research institutes, in social care services or in the private sector.

How is research funded?

Research that takes place in the NHS may be paid for by one of a variety of different organisations, and often more than one working in partnership. They include:

• the NHS, through the National Institute for Health Research 
• the Medical Research Council 
• the Department of Health and other government departments 
• medical research charities 
• pharmaceutical and other healthcare companies

However the research is funded, the people who take part in it are protected in the same way.

If you are asked to be involved in research, you should be told who is funding it. When research is published, the organisation funding it is usually declared.

How can I get involved?

You can look for research studies yourself, by asking your doctor or a patient organisation, or by looking on the internet. Alternatively, you may be approached to take part in research. Be cautious and don't be afraid to ask questions.

Many different types of health research are going on at any one time.

Some of it may look at the effects of standard treatments, while other research may investigate whether new treatments offer any benefit or how the NHS can best organise and provide services.

The main types of health research, explained below, are:

• clinical research
• observational research 
• laboratory or "test tube" research
• epidemiology
• animal research

Clinical research 

Most research in the NHS involves people, often patients, and is usually referred to as clinical research or medical research.

One particular type of research, the clinical trial, compares the effects, both wanted and unwanted, of two or more treatments. This type of research is described in more detail in the next section about clinical trials.   

Observational research

Observational research uses data collected during routine clinical care to analyse:

• the health of the population
• the natural history of disease 
• the safety and cost-effectiveness of healthcare treatments and therapies used in daily clinical practice

Laboratory or test tube research

Before new medicines are tested in clinical trials, they are tested in laboratories. Only when laboratory research has shown that they are likely to work and unlikely to cause serious side effects will they go on to be tested in clinical trials.

The medicines will often be tested on cells taken from living tissue that are grown and kept alive artificially (cell cultures). These cell cultures cannot survive on their own and once the supply of nutrients, warmth and oxygen is removed, they die.

Research using cell cultures is often called test tube or "in vitro" (meaning "in glass") research, even though much laboratory equipment is now made of plastic.

Cell cultures may, for example, be used to assess the effects of possible drug treatments on cancer cells. Chemicals that are shown to kill cancer cells in the laboratory may be tested in further research as possible cancer drugs.

Epidemiology

Epidemiology is a special branch of research that looks at patterns of illness and disease in groups of people. It tries to identify the causes of disease. 

Some epidemiology studies compare people who have a disease (cases) with people without the disease (controls).

Other studies look at a group of people (a cohort) over time to see what happens. Those who develop a condition and those who do not may then be compared.

A third type of epidemiology study looks at patterns in populations and may find associations between environmental factors, such as diet, and disease.

The main challenge faced by epidemiology is that while studies often identify strong links, they do not prove that one thing has caused the other.

Epidemiology has nevertheless made some of the most important medical discoveries, including:

• smoking tobacco is the main cause of lung cancer  
• the health risks of high-fat diets and lack of physical activity

It may seem obvious now that not smoking and being active are healthy, but this was not always the case (see below).

Animal research

Research on animals is a subject of public debate and controversy and many people have strong feelings about it.

All medicines must, by law, be tested on animals before being given to humans in clinical trials. There are regulations to ensure that animal research is only carried out when there is no alternative, that it is carried out humanely and that it is likely to bring real benefits.

Read more about research and testing using animals on the Home Office website.

Computer models

It is now possible for computers to simulate how the human body works, just as a games console racing game can imitate the way a car works.

The human body is hugely complicated, so computer models cannot yet give reliable findings on how the body really behaves. However, they are already giving useful first suggestions to researchers.

The smoking and lung cancer link

In the 1940s, there were different theories about why there had been such a rapid rise in lung cancer over the previous 30 years.

An initial study of 700 people admitted to hospital with lung cancer revealed that nearly all were smokers. The proportion was much higher than for patients admitted to hospital for other reasons.

A careful follow-up study of 40,000 doctors over three years strengthened the evidence of a link and convinced healthcare professionals of the dangers of smoking.

How research answers what we don't know

There are many questions about health, illness and the effects of treatment for which there are no clear answers. Knowing what the questions are makes it easier to say what future research studies should look at.

For example, there is no medical consensus about the best treatment for an enlarged prostate gland in men (also known as benign prostatic hyperplasia or BPH). The enlargement causes urinary problems, such as increasing the number of times a man has to urinate, having to urinate urgently and reducing the flow of urine.

BPH can be treated with lifestyle changes, medicines or surgery, or by simply keeping an eye on things (known as watchful waiting). There is no convincing evidence that one type of treatment is better than the other, and it may be a matter of personal choice by the doctor or patient, depending on what symptoms the condition causes.

Research is important to try to understand which treatment works best and when.

The right research project

There is benefit in repeating research if uncertainties remain. However, if the answer is already known, it will be more important to move on and ask another research question.

Doctors, researchers and increasingly patients and the public review the research that has been carried out and try to choose research projects that look at important unanswered questions.

Research ethics committees now ask researchers and others seeking approval for new trials to show that they have already reviewed previous research systematically (systematic reviews). If they do this, researchers are more likely to choose an appropriate research project and get an answer that will be helpful to patients.

Collecting together what is unknown

Researchers and scientists have, for centuries, made huge efforts to collect together what they know in medical libraries and, more recently, in electronic databases. Now, researchers are collecting what they are not sure about in the UK Database of Uncertainties about the Effects of Treatments (UK DUETs).

The main aim of DUETs is to help people decide which of the unanswered questions are most important, such as how prostate cancer should be managed (see below)

DUETs identifies the need for future research using guidelines from the National Institute for Health and Clinical Excellence (NICE) and other publications that highlight gaps in knowledge.

Researchers also have increasing interest in the questions that matter to people who are ill, their families and those who care for them. The James Lind Alliance helps patients and medical professionals decide which uncertainties should be prioritised for further research.

Managing prostate cancer

There are uncertainties about whether it is a good idea to diagnose prostate cancer early. This is because the disease is often so slow moving that it does not become serious.

There are also uncertainties about how best to investigate possible cases of prostate cancer and how to treat them. Only good research can address and reduce these uncertainties.

How does it work?

A clinical trial is a particular type of clinical research that compares one treatment with another. It may involve patients or healthy people, or both.

Small studies produce less reliable results than large ones, so studies often have to be carried out on a large number of people before the results are considered sufficiently reliable.

Why clinical trials are important

Doctors and other healthcare professionals and patients need evidence from clinical trials to know which treatments work best. Without this evidence, there is a risk that people could be given treatments that have no advantage, that waste NHS resources, and that might even be harmful.

Clinical trials help determine whether:

• treatments are safe 
• treatments have any side effects 
• new treatments are better than available standard treatments

Many NHS treatments have been tested in clinical trials.

The evidence for some treatments is incomplete (see above for more about what we don’t know). The NHS aims to inform patients about research that is relevant to them and offer more patients the opportunity to take part in clinical trials, if they want to.

What clinical trials can find out

Clinical trials can help:

• prevent illnesses by testing a vaccine 
• detect or diagnose illnesses by testing a scan or blood test 
• treat illnesses by testing a new medicine 
• find out how best to provide psychological support  
• find out how people can control their symptoms or improve their quality of life by testing how a particular diet affects a condition

Trials follow a set of rules, known as a protocol, to ensure that they are as safe as possible, that they measure the right things in the right way and that the results are meaningful. A full protocol should be available to anyone who is considering taking part in a trial and wants to see it.

Many clinical trials are designed to show whether new medicines work as expected. These results are sent to the Medicines and Healthcare products Regulatory Agency (MHRA). The MHRA then decides whether to allow the company making the medicine to market it for a particular use.

See below for  more about safety and regulation.

Entering a trial    

If you're receiving treatment for a medical condition, you may be asked if you would like to be part of a trial. You might be interested in finding out about trials that are taking place so that you can volunteer to be part of one. Read more about taking part in clinical trials, including how to join a trial.

The James Lind Library 

The James Lind Library contains books and essays explaining how fair tests are carried out. If you want to find out more about medical research, you can download books for free from their website, including how to make smart health choices and understanding health statistics. 

Clinical trial phases

All clinical trials of new medicines go through a series of phases to test whether the medicines are safe and whether they work.

The medicines will usually be tested against another treatment, called a control. This will either be a substance containing no medication (a placebo) or a standard treatment that is already in use.

Early research may involve volunteers (who may or may not have a health problem) attending a clinic to assess the effects and safety of a new treatment. Students are often thought of as the typical participants in this type of research, but in fact all kinds of people do it.

You may see advertisements looking for volunteers in newspapers. There may be a payment for this kind of research and usually your expenses will be paid.

From these beginnings, clinical trials become larger and more complicated as the tests of safety and effectiveness become more strictly regulated. 

Phase one trials

Phase 1 trials aim to test the safety of a new medicine.

A small number of people - who may be healthy volunteers - are given the medicine and researchers test for side effects and calculate what the right dose might be to use in treatment (known as dose-ranging studies).

This will usually be the first time that the medicine has been tried on humans, so there is an unavoidable element of risk. To minimise this risk, researchers start with  small doses and only increase the dose if the volunteers do not experience  any side effects, or if they only experience minor side effects.

Phase two trials

Phase 2 trials test the new medicine on a larger group of people who are ill, to get a better idea of whether it works, and how well it works in the short term.

Phase three trials

Phase 3 trials are only for medicines that have already passed phases 1 and 2. They test the medicine in larger groups of people who are ill, and compare the new medicine against an existing medicine, or a placebo, to see if it works better in practice and if it has any important side effects. Phase three trials often last a year or more and involve several thousand patients.

Phase four trials

Phase 4 trials take place once a new medicine has passed all the previous phases and has been given marketing licences. A marketing licence means the medicine can be made available on prescription.

In phase four trials, the safety, side effects and effectiveness of the medicine continue to be studied while it is being used in practice. Phase 4 studies aren’t required for every medicine.

Similar trials are used to assess the effects, both wanted and unwanted, of other kinds of treatment, including physical therapies, surgery, psychological therapies and ways of organising care.

More information

Read more about the development of medicines (PDF, 176kb) from the Association of the British Pharmaceutical Industry.

Fair tests

Not only do unproven treatments need to be tested, but the tests also need to be fair. Without a fair test, the findings from any research may not mean much. Even worse, an unfair test could give healthcare professionals the wrong idea and people may be given treatment that does not work, or they may not be given treatment that could be helpful.

This section explains:

• making comparisons
• placebo effect 
• control groups 
• randomisation 
• blinding
• size of trials
• more information

Making comparisons

If someone who is ill takes a treatment and then gets better, it could be due to a natural recovery that would have happened anyway.

To tell if the treatment has worked, it needs to be compared to another treatment or a placebo (see below). The two results have to be different enough to indicate a difference has not occurred by chance.

Comparing a treatment with a placebo

The treatment may be compared with a placebo (a dummy treatment), such as a sugar pill, that looks the same as the treatment.

If there are fewer symptoms after a treatment than after a placebo, this suggests that the treatment works.

Comparing a treatment with a standard treatment

Where a treatment is already known to be effective from previous research, it is usually not considered right (ethical) to compare the new treatment with a placebo. The new treatment usually needs to be compared with a standard treatment that is already known to be helpful.

This makes it possible to determine whether the new treatment works better than the treatment already being used.

 Placebo effect

The placebo effect is the phenomenon of someone’s symptoms improving when they have only been given a dummy treatment, or even after they have just seen a doctor.

Sometimes, a doctor's or other healthcare professional’s reassurance and their confident way of communicating with people who are feeling ill helps some people to feel better. The placebo effect is a largely mysterious and fascinating effect that can be quite powerful.

If you think and believe you are going to get better, you're much more likely to. However, this doesn't work in all situations and for all conditions.

Dummy treatments (placebos) may be given to people in clinical trials. A placebo medicine looks the same as the medicine being studied, so you don't know which one you're taking. Some people may feel better after taking the placebo medicine because they think they are being given real medication. This is the placebo effect.

Placebos are particularly powerful in conditions where symptoms are important. For example, people feel pain differently and respond better to treatments they think are going to work. In extreme circumstances, some people who are in severe pain respond to a placebo apparently as well as they would to a powerful painkiller.

Placebos do not work for all conditions. High blood pressure can be lowered by active medicines, but placebos have no detectable effect. Similarly, placebo treatments do not lower blood cholesterol, but statin medicines do.

Sham treatments that work

Researchers have designed ways of creating placebos for complementary medicine treatments, such as acupuncture. It's possible to carry out sham acupuncture where needles are inserted to a different depth and in different places than those used in real Chinese acupuncture. In recent trials, both types of acupuncture appeared to be better than doing nothing.

Studies have also carried out placebo surgery on people with knee pain. The placebo treatment often has good results.

Control groups

Participants in a clinical trial will usually be put into one of two groups: 

• a group in which they are given the unevaluated treatment being assessed 

• a group in which they are given an existing standard treatment or a placebo if no proven standard treatment exists

The aim is to compare what happens in the comparison groups. Participants are randomly assigned to one of these groups (see randomisation, below).

While treatments are different in the two groups, as many other conditions as possible stay the same. For example, both groups should have people of a similar age, with a similar proportion of men and women, who are in similar overall health.

Randomisation

The best way to get similar groups is to allocate individuals to one of the groups in the trial in an unpredictable, random way. This increases the likelihood that the two groups will be similar. This process is called randomisation.

In most trials, a computer rather than a doctor will randomly decide which group each patient will be allocated to. This allocation will be concealed until after each eligible patient has been accepted for the trial.

These precautions mean that people who decide whether a patient is eligible to participate in the trial cannot influence which treatment a patient is allocated to receive. This protects the study from conscious or unconscious bias, which would make the test unreliable.

Placebo effects

• Four placebo tablets work better than two in gastric ulcers.
• Pink dummy pills are better at maintaining concentration than blue ones.
• Placebo injections are more effective than placebo pills.
• Painkillers work better if they are believed to be costly than if they are believed to be cheap.

(Source: Bad Science, Ben Goldacre, Fourth Estate, 2008)

Blinding

Many trials are set up so that no one knows who has been allocated to receive which treatment. This is known as blinding and helps reduce the effects of bias when comparing the outcomes of the treatments.

Many people feel better if they think they're getting a better new treatment, even if the treatment is ineffective and their underlying health problem has not really changed at all.

When both the medical staff organising the treatment and those taking part in the trial do not know who is receiving which treatment, it is called a double-blind trial.

Blinding is easier when testing medicines, but more difficult when testing other types of treatments or methods of caring for people. For example, it may be impossible to blind a trial that is comparing two types of surgery.

Why blinding is important

Some clinical trials measure hard outcomes such as survival, so outcome measurement is unlikely to be biased.

However, most trials measure outcomes that are more open to biased assessment. For example, patients and researchers may have to make some sort of judgement about how bad symptoms are.

If either researchers or participants know, or think they know, who is receiving which treatment (including placebos), that knowledge may influence what they report.

Participants who think that they are taking an active treatment may not want to let down the researcher, and may exaggerate benefits and minimise side effects. Researchers may allow their hopes about a new treatment to unconsciously influence their recording of symptoms.

The result of these biases is often to overestimate how effective a treatment is. To reduce these possible sources of bias, many trials are double-blind.

Size of trials

For a trial to be a fair test, the number of people taking part needs to be large enough.

For example, in a small trial of 20 people with 10 people taking each treatment, seven people may improve on the new treatment and five on the standard treatment.

Most of us would not think of that as a fair test because, while the new treatment may be better, the finding could easily have occurred by chance.

If the trial was bigger, with 700 out of 1,000 people improving on the new treatment and 500 out of 1,000 on the standard treatment, the result means researchers can be very confident that the new treatment was better.

The degree of this confidence can be estimated. Researchers can provide a range, called a confidence interval, to tell you how certain they are of the result. Learn how to interpret confidence intervals in scientific studies with this online tool from Oxford University.

Researchers can also test how "statistically significant" a result is. This can help identify where differences between treatments are unlikely to be due to chance.  

More information

Read more about fair tests in the James Lind Library. You can also download books for free, including how to make smart health choices and understanding health statistics. 

Reducing the effects of chance

If you toss a coin three times, there is a one in eight chance it will come up heads every time. But if you toss it 10 times, the chance of it being heads every time is about 1 in 1,000.

In a fair test, 10 heads in a row is unlikely. So trials with more people provide more reliable evidence. It is like tossing the coin more often.

How is it performed?

Research is not just for researchers. The public can be involved, too. New research cannot lead to reliable findings unless the right patients agree to join in.

Clinical trials

One type of health research is the clinical trial, which compares one treatment with another. 

If you take part in a clinical trial, you may be one of the first people to benefit from a new treatment. Or, when you have a standard treatment as part of a clinical trial, you can help to test whether that treatment is better and safer than a different standard treatment.

Other health research

The public can also get involved in other types of health research.

For some types of research, people are asked whether researchers may use personal information, in confidence, from their health records.

For other types of research, it is not necessary for the researchers to know who the participants are, and they use data from patient information that has been made anonymous.

An organisation called INVOLVE suggests ways that people can contribute to research without taking part in a trial. When the public is involved in the way research is commissioned and managed, it is more likely to produce results that can improve health and social care practice.

This section explains:

• finding out about clinical trials
• questions to ask
• advantages of being in a clinical trial 
• disadvantages of being in a clinical trial
• giving consent
• medical tests
• leaving a trial

Many people choose to take part in clinical trials because it helps increase understanding about a particular disease or condition. This may benefit them or others like them in the future.

Finding out about clinical trials 

If you are ill and interested in taking part in a clinical trial, your doctor or other health professionals may know of research going on that may be right for you. Few health professionals know of all the trials going on in their clinical area. There could be dozens or even hundreds.

Searching the registers

You can look for information on the registers of clinical trials, such as the World Health Organization (WHO) International Clinical Trials Registry Platform. This collects information from different registers to provide a central database of clinical trials.

None of the registers cover all the trials that are currently going on in the UK. However, the UK Clinical Trials Gateway provides information about clinical trials in the UK from several different registers.  

You will probably need to talk to your doctor or specialist nurse about any information on trials that you have found in the registers.  

 Charities

For some conditions, you can find out about trials from patient organisations. For example, CancerHelp (the patient information arm of Cancer Research UK) has clear information on nearly all the cancer clinical trials happening in the UK.

Other health charities also have user-friendly information about some clinical trials. Charities that are not listed may not formally publish lists of clinical trials but may know of some that are relevant to particular conditions.

User-friendly clinical trials information includes:

• Cancer Research UK: find a clinical trial   
• Multiple Sclerosis Society: MS clinical trials   
• Arthritis Research Campaign: arthritis research  
• British Lung Foundation: research   

Questions to ask

When you express interest in a trial, a doctor or nurse is likely to tell you something about it in person. You will also be given some printed information to take away.

You may come back with some questions that you feel have not been answered.

The UK Clinical Research Collaboration is a partnership of organisations that are establishing the UK as a world leader in clinical research. It suggests a number of general and practical questions you may want to ask.

General questions

• What is the aim of the trial and how will it help people?
• Who is funding the trial?
• What treatment will I get if I do not take part in the trial?
• How long is the trial expected to last and how long will I have to take part?
• How long will it be before the results of the trial are known?
• What will happen if I stop the trial treatment or leave the trial before it ends?

Practical questions

• How much of my time will be needed?
• What extra tests or appointments will I have?
• Will I need to take time off work?
• Will I need extra help from family or friends?
• Will you cover the costs of my travel to take part in the trial?
• If the trial is testing a new drug, will I have to collect it from the hospital, will it be sent to me by post, or will I get it through my doctor?
• Will I have to complete questionnaires or keep a diary?
• What are the possible side effects of my treatment?
• How could the treatments affect me physically and emotionally?
• Who can I contact if I have a problem? Will someone be available 24 hours a day?
• How do I find out the results of the trial?

Advantages of being in a clinical trial

The main reason for carrying out trials is to determine whether one treatment is better than another. An advantage of being involved in a trial is that you may be given a new treatment that is better for your condition.

During the trial, your treatment and progress may be monitored more closely than if you were receiving the usual treatment.

After the trial has finished, health professionals will be better able to offer you the most appropriate and effective treatment for you.

Trials are very important in helping find better treatments. By being involved in a trial, you will obtain information and evidence that may be helpful to you in the future, as well as helping the NHS to give people the best possible standard of care.  

Disadvantages of being in a clinical trial

The disadvantages are:

• As with any treatment, you cannot be sure of the outcome. 
• You may be given a new treatment that is not as effective as the standard treatment.
• It is possible that you will experience unexpected side effects.
• You may have to visit your place of treatment more often, or have more tests, treatments or monitoring than you would if you were receiving the standard treatment in usual care. 

Giving consent

You cannot be entered into a trial if you don't want to be. If you're asked to take part, you're free to say yes or no at any time. For children and people under 18, a parent or guardian has to give permission.

The doctor organising your treatment will usually talk to you about being involved. They should explain the possible risks and benefits.

Make sure you are happy with the trial and have been given all the information you want before you give your consent. This may mean taking some time to think about it and talk it over with family or friends, unless a decision is needed urgently because of your medical condition.

If you decide to take part, you will be asked to sign a form to say that you are agreeing to take part in a trial and have understood what that will involve. This is called giving your informed consent.

Why you might not be able to take part

Sometimes, it is not possible for you to be involved in a particular trial. For example:

• Your condition may need to be at a particular stage.
• You may not be allowed to receive another treatment at the same time. 
• Some trials seek people with certain illnesses and conditions, while others need healthy people. 
• Some trials need people of a certain age.
• There may already be enough people in a particular category who have joined the trial.

Medical tests

Before you join a trial you may need to have tests to see if you can take part. You may have to see if  you have raised levels of a particular hormone. This will allow the researchers to know more about your health before you start treatment, so that at the end of the trial they can tell whether there has been any improvement.

During the trial you may have more tests to see whether the treatment is working. It may be possible for the tests to be carried out as part of your routine care or you may have to make more visits than usual to your GP or hospital clinic.

Leaving a trial

You may decide to stop taking part in a trial if your condition is getting worse or if you feel the treatment is not helping you. You can also choose to leave at any point without giving a reason and without it affecting the level of care you receive.

If there are signs that the treatment in a trial could be unsafe, the research team or the regulators will stop the trial.

Results

There may be a delay before the results of a clinical trial are known, particularly with larger trials that can involve thousands of people and many take place over several years.

Even when the results have been collected and analysed, there is a further period, usually several months, when the research is looked at and commented on by other scientists as a check on its quality. This is called peer review.

At the end of the trial the researchers should make the results available to anyone who took part and who said they want to know the results. If the researchers do not offer you the results and you want to know, ask for them.

All the main public funders of health research and the larger medical research charities require researchers to place a copy of their research on UK PubMed Central when it is published. This is a condition of funding.

Licensing a treatment

If research has identified a new medicine, the Medicines and Healthcare Products Regulatory Agency (MHRA) must license it before it can be marketed.

Licensing shows that a treatment has met certain standards of safety and effectiveness.

Safety must be monitored carefully over the first few years of a newly licensed treatment because rare side effects that were not obvious in clinical trials may show up for the first time.

In Wales and England, the National Institute for Clinical Excellence (NICE) decides whether the NHS should provide the new treatment.

On its own, a single piece of research can be misleading. Separate but similar small studies can produce apparently conflicting results, often due to chance.

Collecting information from different trials in an organised way is a powerful method of showing what the overall evidence is. By using a careful "study of studies", called a systematic review, it is possible to distinguish the effects of treatment from the effects of chance.

For example, the first trial to show the benefits of a short course of steroid injections given to pregnant women at risk of having a premature birth was carried out in 1972. A number of later trials had results that were not quite so positive.

Only in 1989 was a "study of studies" of all the trials carried out. It found that babies born to mothers who took steroids were much less likely to die than those whose mothers did not take steroids.

It was not new research that made the difference in this case, but collecting together results from all the existing research.

What are systematic reviews?

Systematic reviews are now an established part of research. They look at all the studies on a topic, not just selected studies that may have a particular point of view and could result in biased conclusions.

For example, contributors to the Cochrane Collaboration, the Centre for Reviews and Dissemination and the Health Technology Assessment programme review all the reliable research about preventing and treating specific health problems and publish it to help patients and clinicians make choices in healthcare.

Systematic reviews often combine findings from separate but similar studies and calculate an overall result. This process is called meta-analysis.

Systematic reviews and meta-analyses are now an important part of health research, because they can identify findings that might otherwise be missed in individual studies.

Research should take place only when a systematic review of previous research has been carried out, and the need for new research has been established.

Read more about systematic reviews in the James Lind Library.    

Safety

How trials are regulated 

People running clinical trials have legal obligations that are set out in the Medicines for Human Use (Clinical Trials) Regulations 2004.

Conditions include:

• Anyone taking part in a trial must have a full understanding of the objectives of the research and any risks and potential inconveniences they may experience when taking part. This information will be given to them at a meeting with a member of the research team.
• A point of contact must be provided so that patients can obtain more information about the trial.

Before a clinical trial of a new medicine can begin, all of the following need to be in place:

• The science the research is based on must be reviewed by experts. 
• The researchers must secure funding.
• An organisation, such as a hospital or research institute, must agree to provide a home base for the trial.
• The Medicines and Healthcare products Regulatory Agency (MHRA) needs to review and approve the trial and issue a clinical trial authorisation (CTA).
• A recognised ethics committee must review the trial and allow it to proceed. 

The MHRA inspects sites where trials take place to make sure they are conducted in line with good clinical practice (an international quality standard).

Industry trials

All trials are regulated, whether or not they take place within the NHS. The Association of the British Pharmaceutical Industry (ABPI) has issued revised guidelines on phase one trials. These and other guidelines on clinical trials can be found on the ABPI website.

Trials of other treatments

The Department of Health’s Research governance framework for health and social care describes how researchers and others are expected to work within a framework of ethical and scientific standards. This applies to all health and social research. It includes:

• promoting good practice
• reducing adverse incidents and ensuring lessons are learned
• preventing poor performance and misconduct

Ethics committees 

Every clinical trial is covered by regulations that protect the health, safety and dignity of the people taking part.

Research ethics committees

All medical research involving people in the UK, whether in the NHS or the private sector, has to be approved by an independent research ethics committee. The committee protects the rights and interests of the people who will be in the trial.

The committees are often based at local hospitals and are formed of local people, such as health professionals, patients, lawyers and members of the public. They have to include members who are not health professionals.

Submitting a protocol

Before they start a trial, researchers have to submit a detailed plan of their proposed research (protocol) to a recognised research ethics committee. They may also need approval from other regulators.

All clinical trials of medicines need to be authorised by the Medicines and Healthcare products Regulatory Agency (MHRA), as do studies on medical devices.

An online system called the Integrated Research Application System allows researchers to use a single set of information to apply to the research ethics committee and to other regulators.

Patient information

Researchers have to prepare an information leaflet about their trials for patients. The research ethics committee checks that this is clear and accurate.

All those who take part in the trial are given the leaflet, with an opportunity to take it away and discuss it with friends and relatives.

The leaflet has to be in plain language, avoiding technical medical words. It has to make clear:

• the research questions that the trial is trying to answer
• who can take part in the trial and who cannot
• how those taking part in the trial will be treated and what they will need to do
• what treatment or other intervention is being used
• what type of research it is
• what the possible risks are to participants
• what the possible benefits are to participants
• who is carrying out the trial and who is funding it 
• who participants should talk to if they have further questions

Until a research ethics committee approves a clinical trial, researchers cannot ask any participants to join it.

The committees are independent both of the researchers whose work they are reviewing and of those who pay for the research.

The ethics committees that review clinical trials in the NHS are part of the National Research Ethics Service. This service is beginning to publish plain-language summaries of clinical trials that are understandable by anyone.

Review committees

Some longer clinical trials that produce a lot of information over several years have early warning systems that help identify whether the benefits of a treatment or intervention are so good, or the potential risks so high, that the trial should be stopped early.

In a large trial that lasts several years, a data monitoring committee, which is independent of the running of the trial, will look at the information being produced by the trial earlier than the researchers. The committee members look at results at fixed intervals, or when a reason for investigation emerges in between.

Trials should be stopped if it becomes obvious that one of the treatments being compared is clearly better or worse than the other.

However, if things are going as expected with no completely clear signals that one treatment is better, the committees will recommend that researchers carry on as intended.

When things go wrong

Medical research and clinical trials are carried out by health professionals whose training and everyday work is focused on the care of patients.

This work is regulated by laws and codes of conduct and is approved by local research ethics committees, whose purpose is to protect the interests of people taking part in the research.

Generally, clinical trials are safe, but sometimes things go wrong.

The Northwick Park trial

In March 2006, six men had severe and life-threatening reactions during a clinical trial. They were in a private research unit in northwest London in a trial for an experimental treatment that might have been developed to treat leukaemia or rheumatoid arthritis.

The trial was the first time that the treatment, TGN1412, had been used in people (a "first-in-man" trial). All previous research on TGN1412 had been in animals.

The men had serious symptoms, including vital organ failure, fever and low blood pressure. They had to be treated in the intensive care unit at the NHS Northwick Park Hospital in Middlesex. The men survived, but their health was permanently damaged.

A detailed investigation into what went wrong recommended many changes to the way first-in-man trials are carried out. Those recommendations have now been put in place.

What happened to the six men in the trial was widely reported in the media. It was shocking but highly unusual. Nothing of the same scale has been reported before or since in the UK. 

All first-in-man studies, particularly those that use new types of treatment with possibly unpredictable side effects, are now carried out much more cautiously.

With research carried out in the NHS, researchers are likely to have a good idea of possible benefits and side effects of treatment. Researchers have to make the medical background clear and describe details of any new treatments or other interventions being carried out.

More information

Read more from the expert report on first-in-man trials.

Regulating animal research

There are extensive regulations to ensure the welfare of animals in research.

These include regular inspections from government officials and a requirement for researchers to explain their research ideas and pass an approval process before they start. 

Read more about research and testing using animals on the Home Office website.

Selected links

NHS Direct Wales links

Medicines information

External links

National Institute for Health Research

Medical Research Council

Economic and Social Research Council

Association of Medical Research Charities

Association of the British Pharmaceutical Industry

Association of British Healthcare Industries

James Lind Alliance

Understanding Animal Research

National Research Ethics Service

Medicines and Healthcare products Regulatory Agency

Integrated Research Application System

Database of Uncertainties (DUETs)

INVOLVE

UK PubMed Central

Healthtalkonline: clinical trials

UK Clinical Research Collaboration