A positive approach

to psoriasis and

psoriatic arthritis

Clinical Trials:An Overview

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What are the aims of this leaflet?This information is intended to help you understand howtreatments for psoriasis or psoriatic arthritis aredeveloped, what a clinical trial involves and what toconsider if you are volunteering.To learn more about psoriasis and psoriatic arthritis, seeour leaflets What is Psoriasis? and What is PsoriaticArthritis?

Introduction to treatmentsThere are many availabletreatments for psoriasis andpsoriatic arthritis, includingtopical applications tothe sk in , sys temictherapies taken as tabletsand liquids, injections,physical therapy, surgery,light treatment, mechanicalp a i n r e l i e f , t a l k i n gtherapies, se l f -he lp andcomplementary supplements thatmight include dietary interventions. For more information,see our leaflets Treatments for Psoriasis: an overviewand Treatments for Psoriatic Arthritis: an overview.Some treatments for psoriasis and psoriatic arthritishave been around for decades, such as tar treatmentsand UV light treatment for psoriasis, and anti-inflammatory drugs for psoriatic arthritis. However, asscientists have gained a better understanding of theimmune system and how psoriasis and psoriatic arthritisdevelop, new treatments have become available.It can take many years after discovery/invention for atreatment to become available for doctors to prescribe. Apharmaceutical company will spend millions of poundsover the course of a drug development process in thehope that the future treatment becomes successful andprofitable. Many potential therapies are never developedas a medicine. Overall, approximately 1 in 10,000 potentialmedicines makes it all the way through the process toreach patients.

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The process of drug development is focused ondelivering safe and effective treatments. The process islong, since treatments are initially developed in thelaboratory, with extensive scientific testing of short- andlong-term effectiveness, possible side effects, anyimplications of taking the new drug in combination withexisting medicines, optimal dosage and suitable ways toadminister the treatment.A potential new medicine which is in development isnamed an Investigational Medicinal Product (IMP) toseparate it from an authorised medicine. Once an IMP haspassed laboratory investigations, the pharmaceuticalcompany in control of the IMP will apply for permission toconduct a clinical trial of its use in humans.

What is a clinical trial?Most research in the National Health Service (NHS)involves people, often patients, and is usually referred toas clinical research or medical research to evaluatemedical, surgical or behavioural intervention.

Clinical trials may compare anew medical approach too n e t h a t i s a l r e a d yavailable or to a placebo(a substance that hasno therapeutic effect)or to no intervention atall. Some clinical trialscompare interventionsthat are already available.

A clinical trial may beresearching a particular IMP,and may therefore be called a Clinical Trial of anInvestigational Medicinal Product (CTIMP). However, thetrial may also be looking at medical devices, procedures,or changes to participants' behaviour, such as their diet.

When a new product or approach is being studied, it isnot usually known whether it will be helpful, harmful, orno different from available alternatives (including nointervention). The investigators try to work out the safetyand efficacy (effectiveness) of the intervention by

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measuring certain outcomes. For example, they canmeasure how psoriasis or psoriatic arthritis improves byusing a scoring system.Clinical trials used in drug development are sometimesdescribed by phase. This highly controlled process isregulated by the Medicines and Healthcare productsRegulatory Authority (MHRA), which is the governmentagency responsible for making sure medicines andmedical devices work and are acceptably safe.

How is a clinical trial planned?A CTIMP of a potential new medicine for psoriasis orpsoriatic arthritis may involve a large number of people orgroups, including the following.

n Pharmaceutical companyThe company which owns and has developed the IMPin the laboratory will organise the clinical trialsnecessary to develop the IMP for humans

n A contract research organisationClinical trials are sometimes conducted by a contractresearch organisation, which is an independentcompany with specific scientific expertise

n Specialist doctors and nurses

From the relevant specialty, such as dermatology forpsoriasis or rheumatology for psoriatic arthritis.

These people or groups will decide the best way toinvestigate the IMP. The first stage involves writing a verydetailed document containing all relevant informationabout the IMP and a plan that describes how the clinicaltrial will be conducted, where and by whom. This is calledthe clinical trial protocol. Once a clinical trial protocol is inplace, a request for clinical trial approval is made.

What’s included in a clinical trialprotocol?n The name and description of the new treatment

n A summary of findings of other studies already carriedout

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n When and how the patient uses or takes the treatment

n A description of the population to be studied

n A detailed description of trial design, including themeasures taken to avoid bias

n The expected duration of participation

n A description of the stopping rules (when a trial ortreatment stops or a participant needs to withdraw).

Evaluations

n Methods, timing and specification of the efficacy andsafety parameters

n Procedure for generating reports and reporting anyside effects and intercurrent illnesses (an illnesshappening at the same time and which may affect theillness being tested)

n Description of the statistical procedures for analysingthe data obtained during the trial.

General information

n Name and address of the pharmaceutical companycarrying out the trial

n Name and address of the investigator carrying out thetrial

n Name and address of anybody else involved in theconception, design and carrying out of the clinical trial.

Regulatory section

n Financing and insurance of the study

n Data handling and record-keeping procedures

n Description of the ethical considerations relating to thetrial

n Description of quality control and quality assurance tobe adopted during the trial.

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The process for approval is complex in order to ensurethe research is justified and acceptably safe. A key part ofthe process is ethical approval. This is where the clinicaltrial protocol is submitted to an ethics committee – anindependent group of people, appointed by the localhealth authority, which includes doctors, nurses, medicalstaff, lawyers and members of the public. They will decidewhether the research is justified, including checks thatthe:

n researchers are qualified to carry out the trial

n protocol is suitable for the needs of the trial

n probable benefits of a new treatment outweigh therisks of side effects

n information given to participants is sufficient

n way in which people will be recruited is correct

n local health facilities can support the trial.

Once the ethics committee has approved the protocol,other formal approvals must follow and once these are allcomplete, the clinical trial may begin.

Types of clinical trialsClinical trials may be divided into types, or phases. Eachnew IMP must proceed through the phases in turn. Unlessthey pass each phase, they cannot proceed to the next.

Phase one:

Phase one clinical trials are the first time that a potentialnew medicine or other intervention is given to a humanbeing. This is done using a small number of healthyvolunteers. The main aim of a phase one trial is to checkthat there are no serious side effects, known as adverseevents, with the planned dose of the potential medicine.Phase one studies go ahead with extreme caution toprevent multiple side effects; each volunteer is closelymonitored by doctors and research staff. The trial startsby giving healthy volunteers very small doses of thepotential new medicine, then increasing the dose to checkwhat doses are acceptably safe.

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Phase two:

Phase two studies involve giving the IMP to a slightlylarger group, this time consisting of patients rather thanhealthy volunteers. For example, a phase two clinical trialof a potential new treatment forpsoriasis would go aheadwith the help of specialistdermatology centresand overseen by asenior dermatologist.Here, a key aim is tofind out whether themedicine dose whichw a s f o u n d t o b eacceptably safe in the firstphase actually works for thedisease it is intended to treat. Safety is vital and any sideeffects are analysed. In phase two testing, the patientsselected for testing usually share very similarcharacteristics, such as their age range. One reason forthis approach is that if any problem occurs, theresearchers can prove that it was due to the medicinerather than because of any other medical conditions thevolunteers suffer from.

Phase three:

A phase three study tests the medicine on a larger groupof patients. In phase three trials, patients treated with thenew product may have other medical problems, ratherthan sharing similar characteristics as in a phase two trial.This is to ensure that all types of patients can besuccessfully and safely treated with the new medicine.Often, trial populations are not truly representative of thegeneral psoriasis or psoriatic arthritis population.At the end of phase three, the information needed forthe product information leaflet (PIL) and drug label will becompleted.

Phase four:

Once a drug has completed phase three trials, thepharmaceutical company will apply for a medical licence

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for the drug to become available for doctors to prescribe.Although, this is not the end of the process, in the interestof safety, continuous monitoring of the drug takes place.This will include doctors and patients reporting anyadverse events.

TerminologyThere is a lot of medical jargon involved in explainingtypes of clinical trials. It is essential that anyone involvedin any type of research completely understands theprocedure, has all the facts and gives consent to takepart. Any researcher must be responsible for minimisingjargon used and explaining any unclear terms. Below aresome of the terms used when discussing clinical researchtrials.

Randomised and blinded trialsWhen someone takes part in a research trial whichinvolves testing one treatment against another or againsta placebo, the treatment will usually be based onrandomisation, which means that the treatment for eachpatient is chosen at random (the researcher may give thevolunteer a number rather than the name of treatment);participants cannot choose theirtreatment.The researcher in charge ofthe trial may or may not beaware of which treatmenteach participant receives.If they are not aware, thetrial is known as blind.The medicine that all thepatients are given will lookthe same, whether it is thenew treatment, an existingtreatment, or a placebo.A double-blinded clinical trial is where neither thevolunteer nor the person in charge of the clinical trialknows which treatment is being used.

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This process of randomisation and blinding is designedto make sure that any positive effect of a new medicine isbecause the treatment is effective, and not becauseresearchers chose patients who were more likely torespond positively. While there may be no doubt that theclinical trial is being carried out properly, these processesare used as proof to a l l medica l profess ionals that the research has been conducted to the higheststandards.

Placebo-controlledA placebo is an inactive dummy treatment that may begiven instead of the drug being tested. A placebo is usedto prevent volunteers, and often researchers, knowingwhether they are taking the potential treatment or not.Consciously or otherwise, knowing they’re taking the drugcan affect the results of a trial. A placebo-controlled trialis a clinical trial where a placebo is used to test resultsagainst those of the potential treatment.

Who is in charge of the clinicaltrial?The person in charge of a clinical trial is called the chiefinvestigator (CI). The CI may oversee trials taking place inmany centres across the UK. The person in charge of onehospital’s volunteers is called the principal investigator(PI). The person who asks people to take part in a clinicaltrial (typically a doctor, nurse or researcher) should have allthe information a volunteer may need to know about thestudy. Any information about a trial which is distributedshould contain the CI’s name and the name and contactdetails of someone who can be contacted with questionsin the event of an emergency.

Why are people asked to takepart in clinical trials?Clinical research is vital to improve the lives of people withdiseases by enabling improvements in healthcare. No new

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medicines would become available unless volunteers tookpart in clinical trials, because products must beconsidered safe and effective before being made morewidely available.

Who can participate in clinicaltrials?Each trial will have a defined set of criteria to work outwho can volunteer for which trial. Each volunteer is askeda set of questions to decide whether he or she wouldqualify for the clinical trial. For example, if a patient haspsoriasis without psoriatic arthritis, it would not be usefulto hear all the details of a clinical trial for a treatmentrequiring volunteers to have both.Where a clinical trial requires a change in treatments, aparticipant must consider how their psoriasis or psoriaticarthritis may respond to time with no treatment or tochanges in treatment, and the possibility that newtreatments may not necessarily be effective for thedisease at all.

What questions should volunteers ask?Most practical questions will be answered in the patientinformation leaflet, a mandatory leaflet which is given toany potential research volunteer. Below are some of thequestions often asked.

n What is the aim of the research?

Clinical research should be carried out with the aim ofachieving specific improvements and these should beclearly explained by the researcher asking you to takepart.

n Who qualifies?

Many research projects have specific lists of the typesof patients, such as their age when their condition first developed, which treatments they currently use, etc.

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n What is the point of the trial and how will it

help people?

Participants should feel satisfied that the trial isworthwhile and that the trial is seeking to answer auseful question.

n How long will the clinical trial last?

This varies greatly but must be practical for thevolunteer. Considerations to take into account includethe venue, frequency of visits and any impact on workor family life.

n Will travelling expenses be reimbursed?

This is something that needs to be considered giventhat it may require attendance on a regular basis.

n Can trial participants withdraw at any time?

All ethics committees require this for all trials. Patientshave the right to withdraw at any time; they do nothave to give a reason if they prefer not to.

Remember: all participation in research is entirelyvoluntary and volunteers should never feel in any wayobliged to take part. Any volunteer who later changes theirmind must always be allowed to make this choice.

What will a trial participant beasked to do?This will depend on the clinical trial and can becomplicated. Generally, for bothpsor ias is and psor ia t icarthritis, there may be a number of c l in ica lassessments to under -t a k e . T h e s e w i l lpossibly be overseenby a nurse, and mayinclude blood pressure,p s o r i a s i s s c o r e s ,measurements of pain andsw e l l i n g i n j o i n t s e t c .

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Sometimes blood, or skin samples in the form of a skin biopsy, might be taken to assess and measureother benefits or risks that you may not be able to notice.

Psoriasis and psoriatic arthritis are known to affectquality of life, to varying degrees depending on theindividual. Many studies use questionnaires to assess this.It may seem that some of the questions asked during atrial are rather unnecessary and may be more detailed orpersonal than you expect.

Participants don’t have to answer if they don’t want to,but researchers are trying to assess the full impact of theconditions from a patient’s perspective, so more detailedinformation can benefit the trial.

Questionnaires are designed to see how the conditionaffects you and whether the intervention or treatment hasimproved or helped you to feel better.

You may be asked to use a new treatment, an existingtreatment or in some cases a dummy treatment (placebo)if the trial is comparing the effectiveness of newcompounds such as a tablet, cream or injection.

At all times you will be asked to report the benefits andany adverse events (side effects) that you haveexperienced. These will all be included in the datacollection to provide an accurate assessment of thebenefits and risks, which usually can only be obtainedfrom real people who act as volunteers within a clinicaltrial.

What are the risks and benefits of taking part in a clinical trial?Participants will be monitored carefully during and afterany trial. They will have regular evaluations and willsometimes be asked questions about how they are feelingin general. This process might mean going to the hospitalmore regularly than usual.Taking part in a clinical trial does not guarantee bettertreatment, nor will it automatically guarantee receiving thetreatment being tested. However, because participantsare so closely monitored, any changes, for better or forworse, will be quickly picked up and acted upon.

Being part of a research trialhelps to improve scientificu n d e r s t a n d i n g o fpsoriasis and psoriaticarthritis and the bestmeans of treatment.However, this does not mean tha t anyoneshou ld fee l ob l iged to take part and it is alwayspossible to withdraw from atrial at any time.

What should researchers tellparticipants?Researchers, or anybody else who suggests taking part ina trial, should explain everything about the study andanswer any questions.

n They cannot give out a copy of the protocol, since thisis a scientific document containing confidentialinformation

n They should give volunteers a leaflet or fact sheetabout the trial, which can be taken away and read atleisure

n Volunteers will be asked to give written consent.Withdrawing or refusing consent will not affect overallcare and doctors will not hold itagainst them.

A new treatment mayhave side effects thatcannot be predicted.Th is i s why i t ’s soimportant to have thename and number of acontact for the clinicaltrial to contact in the eventof an emergency.

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How can I find out more aboutclinical trials in psoriasis orpsoriatic arthritis?You can ask your general practitioner, nurse,dermatologist or rheumatologist. More widely, clinicaltrials are advertised via newspapers, TV, radio, online andsocial media. Sometimes hospitals will advertise on theoutpatient notice board and on their websites.You may also find the following website useful:www.nhs.uk/Conditions/Clinical-trials

Are there guidelines aboutresearch?Yes, there are guidelines for researchers about the sort ofinformation that volunteers need in order to decidewhether to take part in a clinical trial. However, there is alot of debate about how much information volunteersactually require, since this varies from person to person.The important thing is that participants are satisfied thatthey have enough information to make an informeddecision. So, you should feel free to ask any questionsand be given enough time to consider your options beforemaking a decision. Remember, if you are consideringtaking part in a trial you are always free to discuss thisdecision with friends and relatives, and even otherhealthcare providers, including your general practitioneror a specialist, BEFORE you take part.

About this informationThis material was produced by PAPAA. Please be awarethat research and development of treatments is ongoing.

For the latest information or any amendments to thismaterial, please contact us or visit our websitewww.papaa.org. The site contains information ontreatments and includes patient experiences and casehistories.

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This material was reviewed and fully revised in 2012 byDr Amy Foulkes, MRC clinical research fellow based atthe University of Manchester, and by Dr Laura Coates,consultant rheumatologist and NIHR clinical scientist,University of Oxford and Nuffield Orthopaedic Hospital, inFebruary 2016 and January 2019, with minor editorialrevisions by PAPAA in January 2020.

A lay and peer review panel has provided key feedbackon this leaflet. The panel includes people with or affectedby psoriasis and/or psoriatic arthritis.

Quality and accuracy The standard by which we produce information is basedon the Information Standard scheme that was developedby the Department of Health and administered by NHSEngland. The scheme ended on 31 July 2019.

As a former member organisation of the scheme, wehave committed to continue to uphold the principals ofthe scheme and will produce material that is clear,accurate, evidence-based, up-to-date and easy to use,which allows people, patients and communities tobecome better informed and more involved in their healthand care.

Published: 2020

Review date: 2023

© PAPAA

The charity for peoplewith psoriasis and psoriatic arthritis

PAPAA is an organisation that is independentlyfunded and a principal source of psoriasis

and psoriatic arthritis information andeducational resource.

PAPAA supports both patients and professionalsby providing material that can be trusted

(evidence based), which has been approved andcontains no bias or agendas.

PAPAA provides positive advice that enablespeople to be involved, as they move through their

healthcare journey, in an informed way which is appropriate for their needs and any

changing circumstances.

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