Clinical Trials: An overview

Transcription

1 Cliical Trials: A overview A positive approach to psoriasis ad psoriatic arthritis

2 What are the aims of this leaflet? This iformatio is iteded to help you uderstad how treatmets for psoriasis or psoriatic arthritis are developed, what a cliical trial ivolves ad what to cosider if you are voluteerig. Cotets: About psoriasis ad psoriatic arthritis What happes i psoriasis? What happes i psoriatic arthritis? Itroductio to treatmets What is a cliical trial? How is a cliical trial plaed? Types of cliical trials Who is i charge of a cliical trial? Why are people asked to take part i a cliical trial? Who ca participate i a cliical trial? What questios should voluteers ask? What might a voluteer be asked to do durig a cliical trial? What are the risks ad beefits of takig part i a cliical trial? Further sources of iformatio about cliical trials About psoriasis ad psoriatic arthritis Psoriasis (sor-i ah-sis) is a log-term (chroic) scalig disease of the ski that affects 2%-3% of the UK populatio. It usually appears as red, raised, scaly patches kow as plaques. Ay part of the ski surface may be ivolved but the plaques most commoly appear o the elbows, kees ad scalp. About 10% to 20% of people with psoriasis may develop a associated psoriatic arthritis, which causes pai, iflammatio ad swellig i the joits ad tedos, accompaied by stiffess, particularly i the morigs. 2

3 What happes i psoriasis? Normally a ski cell matures i days ad durig this time it travels to the surface, where it is lost i a costat ivisible sheddig of dead cells. I patches of psoriasis the turover of ski cells is much faster, aroud four to seve days, ad this meas that eve live cells ca reach the surface ad accumulate with dead cells. The extet of psoriasis ad how it affects a idividual varies from perso to perso. Some may be mildly affected with a tiy patch hidde away o a elbow which does ot bother them while others may have large visible areas of ski ivolved that sigificatly affect daily life ad relatioships. This process is the same wherever it occurs o the body. Psoriasis is ot cotagious. For more detailed iformatio o psoriasis see our leaflet What is psoriasis? What happes i psoriatic arthritis? I psoriatic arthritis ad some iflammatory diseases, the immue system does ot work properly, istead causig damage by workig agaist the body's ow tissues. I psoriatic arthritis, iflammatio is characterised by redess, warmth, swellig ad pai. Iflammatio is a process by which the body's ier defece mechaisms - the white blood cells ad other substaces - protect the body agaist ifectio ad foreig ivaders such as bacteria ad viruses. The most commoly affected sites i psoriatic arthritis are the hads, feet, lower back, eck ad kees, with movemet i these areas becomig severely limited. For more detailed iformatio o psoriatic arthritis see our leaflet What is psoriatic arthritis? Itroductio to treatmets There are may available treatmets for psoriasis ad psoriatic arthritis, icludig ski cream treatmets (topical therapies), UV light treatmet (phototherapy) ad tablets ad ijectios. Where do treatmets come from? Some treatmets for psoriasis ad psoriatic arthritis have bee aroud for decades, such as tar treatmets ad UV light treatmet for psoriasis or ati-iflammatory drugs for psoriatic arthritis. However, may ew 3

4 treatmets are available that have bee developed over recet years as scietists have gaied a better uderstadig of the immue system ad how psoriasis ad psoriatic arthritis develops. It ca take may years after discovery/ivetio for a treatmet to become available for doctors to prescribe. A pharmaceutical (drug) compay will sped millios of pouds over the course of a drug developmet process i the hope that the future treatmet becomes successful ad profitable. May potetial therapies are ever developed as a medicie. Overall, oly approximately 1 i 10,000 potetial medicies make it all the way through the process to reach patiets. The process of drug developmet is focused o deliverig safe ad effective treatmets. The process is log, sice treatmets are iitially developed i the laboratory, with extesive scietific testig ito short- ad log-term effectiveess, possible side-effects, ay implicatios of takig the ew drug i combiatio with other, existig medicies, optimal dosage ad suitable ways to admiister the treatmet. A potetial ew medicie i developmet is amed a Ivestigatioal Medicial Product (IMP) to separate it from a authorised medicie. Oce a IMP has passed laboratory ivestigatios, the pharmaceutical compay i cotrol of the IMP will apply for permissio to coduct a cliical trial of its use i humas. What is a cliical trial? Most research i the Natioal Health Service (NHS) ivolves people, ofte patiets, ad is usually referred to as cliical research or medical research. Oe particular type of research, the cliical trial, compares the effects, both wated ad uwated, of two or more treatmets. The cliical trial may be researchig a particular IMP, ad may therefore be called a Cliical Trial of a Ivestigatioal Medicial Product (CTIMP). However, the cliical trial may also be lookig at medical devices, procedures, or chages to participats' behaviour, such as their diet. Cliical trials may compare a ew medical approach to oe that is already available or to a placebo (a dummy medicatio with o active igrediets) or to o itervetio at all. Some cliical trials compare itervetios that are already available to each other. 4

5 Whe a ew product or approach is beig studied, it is ot usually kow whether it will be helpful, harmful, or o differet from available alteratives (icludig o itervetio). The ivestigators try to work out the safety ad efficacy (effectiveess) of the itervetio by measurig certai outcomes. For example, they ca measure how psoriasis or psoriatic arthritis improves by usig a scorig system. Cliical trials used i drug developmet are sometimes described by phase. This highly cotrolled process is regulated by the Medicies ad Healthcare products Regulatory Authority (MHRA), which is the govermet agecy resposible for makig sure that medicies ad medical devices work ad are acceptably safe. How is a cliical trial plaed? A CTIMP of a potetial ew medicie for psoriasis or psoriatic arthritis will ivolve a large umber of people or groups, icludig: l Pharmaceutical compay The compay which ows ad has developed the IMP i the laboratory will orgaise the cliical trials ecessary to develop the IMP for humas l A cotract research orgaisatio Cliical trials are sometimes coducted by a cotract research orgaisatio, which is a idepedet compay with specific scietific expertise l Specialist doctors From the relevat specialty, such as dermatology for psoriasis or rheumatology for psoriatic arthritis. Specialists i the relevat medical speciality will be cosulted ad/or directly ivolved i the applicatio for ad ruig of a cliical trial. These people or groups will decide the best way to ivestigate the IMP. The first stage ivolves writig a very 5

6 detailed documet cotaiig all relevat iformatio about the IMP ad a pla to describe how the cliical trial will be coducted, where ad by whom. This is called the cliical trial protocol. Oce a cliical trial protocol is i place, a request for cliical trial approval is made. A cliical trial protocol will iclude: l Name ad descriptio of the ew treatmet l Summary of fidigs of other studies already carried out l Whe ad how the patiet should apply the treatmet l Descriptio of the populatio to be studied l A accurate descriptio of trial desig, icludig the measures take to avoid bias l The expected duratio of participatio l A descriptio of the stoppig rules (whe a trial or treatmet stops or a participat eeds to withdraw). Evaluatios l Methods, timig ad specificatio of the efficacy ad safety parameters l Procedure for geeratig reports ad reportig ay side effects ad itercurret illesses (a illess happeig at the same time ad which may affect the illess beig tested) l Descriptio of the statistical procedures for aalysig the data obtaied durig the trial. Geeral iformatio l Name ad address of the pharmaceutical compay carryig out the trial l Name ad address of the ivestigator carryig out the trial l Name, address ad telephoe umber of everybody ivolved i the coceptio, desig ad carryig out of the cliical trial. Regulatory sectio l Fiacig ad isurace of the study l Data hadlig ad record keepig procedures l Descriptio of the ethical cosideratios relatig to the trial 6

7 l Descriptio of quality cotrol ad quality assurace to be adopted durig the trial. The process for approval is complex i order to esure the research is justified ad acceptably safe. A key part of the approval is ethical approval. This is where the cliical trial protocol is submitted to a ethics committee - a idepedet group of people, appoited by the local health authority, which icludes doctors, urses, medical staff, lawyers ad members of the public. They will decide whether the research is justified, icludig checks that: l The researchers are qualified to carry out the trial l The protocol is suitable for the eeds of the trial l The probable beefits of a ew treatmet outweigh the risks of side effects l There is eough iformatio give to participats l The way i which people will be recruited is correct l The local health facilities ca support the trial. Oce the ethics committee has approved the protocol, other formal approvals must follow ad oce these are all complete, the cliical trial may begi. Types of cliical trials Cliical trials may be divided ito types, or phases. Each IMP must proceed through the phases i tur. Uless they pass each phase, they caot proceed to the ext. Phase Oe: Phase oe cliical trials are the first time that a potetial ew medicie is give to a huma beig. This is doe usig a small umber of healthy voluteers. The mai aim of a phase oe trial is to check that there are o serious side effects, kow as adverse evets, with the plaed dose of the potetial medicie. Phase oe studies go ahead with extreme cautio to prevet multiple side effects; each voluteer is closely moitored by doctors ad research staff. The trial starts by givig healthy voluteers very small doses of the potetial ew medicie, the icreasig the dose to check what doses are acceptably safe. 7

8 Phase two: Phase two studies ivolve givig the IMP to a slightly larger group, this time with psoriasis ad/or psoriatic arthritis patiets, rather tha healthy voluteers. For example, a phase two cliical trial of a potetial ew treatmet for psoriasis would go ahead with the help of specialist dermatology cetres ad oversee by a seior dermatologist. Here, a key aim is to fid out whether the medicie dose which was foud to be acceptably safe i the first phase actually works for the disease it is iteded to treat. Safety is vital ad ay side effects are aalysed. I phase two testig, the patiets selected for testig usually share very similar characteristics, such as their age rage. Oe reaso for this approach is that if ay problem occurs, the researchers ca prove that it was due to the medicie rather tha because of ay other medical coditios the voluteers suffer from. Phase three: A phase three study tests the medicie i a larger group of patiets. I phase three trials, patiets treated with the ew product may have other medical problems, rather tha sharig similar characteristics as i a phase two trial. This is to esure that all types of patiets ca be successfully ad safely treated with the ew medicie. At the ed of phase three the iformatio eeded for the product iformatio leaflet ad drug label will be completed. There is a lot of medical jargo ivolved i explaiig types of cliical trials. It is essetial that ayoe ivolved i ay type of research completely uderstads the procedure, has all the facts ad gives coset to take part. Ay researcher must be resposible for miimisig jargo used ad explaiig ay uclear terms. Some terms used whe discussig cliical research trials iclude: Radomised ad blided trials Whe someoe takes part i a research trial which ivolves testig either oe treatmet agaist aother or agaist a placebo, the treatmet will be chose at radom (such as the researcher givig the voluteer a umber rather tha a ame of treatmet); participats caot choose their treatmet. The researcher i charge of the trial may or may ot be 8

9 aware of which treatmet each participat receives. If they are ot aware, the trial is kow as blid. The medicie that all the patiets are give will look the same, whether it is the ew treatmet, stadard treatmet, or placebo. A double-blided cliical trial is where either the voluteer or the perso i charge of the cliical trial kows which treatmet is beig used. This process of radomisatio ad blidig is desiged to make sure that ay positive effect of a ew medicie is because the treatmet is effective, ad ot because researchers chose patiets who were more likely to respod positively. While there may be o doubt that the cliical trial is beig carried out properly, these processes are used as proof to all medical professioals that the research has bee coducted to the highest stadards. Placebo cotrol A placebo is a iactive dummy treatmet that may be give istead of the potetial drug beig tested. A placebo is used to prevet voluteers, ad ofte researchers, kowig whether they are takig the potetial drug or ot. Cosciously or otherwise, kowig they re takig the drug ca affect how the cliical trial is ru. A placebo-cotrolled trial is a cliical trial where a placebo is used to test agaist the potetial drug. Phase four: Oce a drug has completed phase three trials, the pharmaceutical compay will apply for a medical licece for the drug to become available for doctors to prescribe. Oce this happes, phase four trials cotiue to moitor use of the drug ad its results, such as ay adverse evets reported by doctors ad patiets, i the iterest of safety. Who is i charge of the cliical trial? The perso i charge of a cliical trial is called the chief ivestigator (CI). The CI may oversee trials takig place i may cetres across the UK. The perso i charge of oe hospital s voluteers is called the pricipal ivestigator (PI). The perso who asks people to take part i a cliical trial (typically a doctor, urse or researcher) should have all the iformatio a voluteer may eed to kow about the study. Ay iformatio about a trial which is distributed should cotai the CI s ame ad the ame ad cotact details of someoe who ca be cotacted with questios i the evet of a emergecy. 9

10 Why are people asked to take part i cliical trials? Cliical research is vital to improve the lives of people with diseases by eablig improvemets i healthcare. No ew medicies would become available uless voluteers took part i cliical trials, because products must be cosidered safe ad effective before beig made more widely available. Who ca participate i cliical trials? Each trial will have a defied set of criteria to work out who ca voluteer for which trial. Each voluteer is asked a set of questios to decide whether he or she would qualify for the cliical trial. For example, if a patiet has psoriasis without psoriatic arthritis, it would ot be useful to hear all the details of a cliical trial for a treatmet requirig voluteers to have both. Where a cliical trial requires a chage i treatmets, a participat must cosider how their psoriasis or psoriatic arthritis may respod to time with o treatmet or to chages i treatmet, ad that ew treatmets may ot ecessarily be effective for the disease at all. What questios should voluteers ask? l What is the aim of the research? Cliical research should be doe with a specific aim of improvemets ad these should be clearly explaied by the researcher askig you to take part. l Who qualifies? May research projects have specific lists of the types of patiets, such as their age whe psoriasis first developed, which treatmets they curretly use, etc. l What is the poit of the trial ad how will it help people? Participats should feel satisfied that the trial is worthwhile ad that it is askig a useful questio. 10

11 l How log will the cliical trial last? This varies greatly but must be practical for the voluteer. Cosideratios to take ito accout iclude the veue, frequecy of visits ad ay impact o work or family life. If attedace ivolves travellig, travel expeses ca be reimbursed. l Ca trial participats withdraw at ay time? The aswer here must be YES. Most practical questios will be aswered i the Patiet Iformatio Leaflet, a madatory leaflet which is give to ay potetial research voluteer. Voluteers should be asked if they have ay questios before voluteerig or takig part. Remember, all participatio i research is etirely volutary ad voluteers should ever feel obliged to take part i ay way. Ay voluteer who later chages their mid must always be allowed to make this choice. Receivig care should i o way deped o voluteerig for research. Questios that should have bee aswered by the researcher iclude: l What are the possible side effects of the treatmet? l Who ca be cotacted if there is a problem? l Will someoe be available to cotact 24 hours a day? 11

12 What might a voluteer be asked to do durig a cliical trial? This will deped o the cliical trial ad ca be complicated. Some commo measuremets that may take place iclude: l Blood or ski samples i the form of a ski biopsy. l Measuremets of psoriasis; this may iclude questioaires to be completed by the participat ad/or a healthcare professioal. The most commo form completed is the Psoriasis Area Severity Idex (PASI). PASI is a measure of how severe psoriasis is, based o lookig at redess, scalig ad thickess of plaques across areas of the body. Researchers may measure psoriasis i other ways. The researcher may ask for opiios rather tha measurig by lookig at the area themselves. l Erythema (redess): The ivestigator will assess the extet of redess o the treated areas. l Dryess: This is defied as tight sesatios o the treated area due to the uusual dryess of the ski. The dermatologist will feel the treated area himself ad ask if the participat has experieced sesatios of this sort durig the treatmet period. l Desquamatio: The abormal sheddig or peelig of the ski. The dermatologist will assess this by lookig closely at the treated area. l Burig: The dermatologist will ask if the participat has experieced ay pricklig pai sesatios at ay time durig the course of treatmet. l Pruritus: The dermatologist will ask if the participat has experieced ay itchig sesatios. l Ifiltratio: This is a simple evaluatio to assess the hardess or firmess of the tissue aroud the lesio. Psoriasis is kow to affect quality of life. So it may seem that some of the questios asked durig a trial are rather uecessary ad quite urelated to the treatmet, such as: l Over the last few weeks, how much has your ski iflueced the clothes you wear? 12

13 l Over the last few weeks, how embarrassed or selfcoscious have you felt because of your ski? l Over the last few weeks, has your ski preveted you from workig or studyig? Voluteers ever have to aswer questios that they are ucomfortable with, but these questios are ofte desiged to see how ad if day-to-day life chages whe treatmet chages. Those with psoriatic arthritis will receive other questioaires, either to fill i themselves or to be completed by their doctor or urse; these measure psoriatic arthritis i terms of severity, which joits are affected etc. There are also further quality of life questioaires that are specifically for psoriatic arthritis as opposed to psoriasis. What are the risks ad beefits of takig part i a cliical trial? There are risks ad beefits to cosider whe participatig i a cliical trial. Whe takig part i a trial, participats will be moitored carefully durig ad after the study. They will have regular evaluatios ad will sometimes be asked questios about how they are feelig i geeral. This process might mea goig to the hospital more regularly tha usual. Takig part i a cliical trial does ot guaratee better treatmet, or will it automatically guaratee receivig the treatmet beig tested. However, because participats are so closely moitored, ay chages, for better or for worse, will be quickly picked up ad acted upo. Beig part of a research trial helps to improve scietific uderstadig of psoriasis ad psoriatic arthritis ad the best meas of treatmet. However, this does ot mea that ayoe should feel obliged to take part ad it is always possible to withdraw from a trial at ay time. What should researchers tell participats? Researchers, or aybody else who suggests takig part i a trial, should explai everythig about the study ad aswer ay questios. 13

14 l They caot give out a copy of the protocol sice this is a scietific documet cotaiig cofidetial iformatio. l They should give voluteers a leaflet or fact sheet about the trial, which ca be take away ad read at leisure. l Voluteers will be asked to give writte coset. Withdrawig or refusig coset will ot affect overall care ad doctors will ot hold it agaist them. A ew treatmet may have side effects that caot be predicted. This is why it s so importat to have the ame ad umber of a cotact for the cliical trial to cotact i the evet of a emergecy. How ca I fid out more about cliical trials i psoriasis or psoriatic arthritis? You ca ask your geeral practitioer, urse, dermatologist or rheumatologist. Ofte cliical trials are advertised i local ad atioal media, icludig ewspapers or o the radio. Sometimes hospitals will advertise o the outpatiet otice board ad o their websites. You may also fid the followig website useful: Are there guidelies about research? Yes, there are guidelies for researchers about the sort of iformatio that voluteers eed i order to decide whether to take part i a cliical trial. However, there is a lot of debate about how much iformatio voluteers actually require, sice this varies from perso to perso. The importat thig is that participats are satisfied that they have eough iformatio to make a iformed decisio. So, voluteers should feel free to ask ay questios ad be give eough time to cosider their optios before makig a decisio. Remember, if you are cosiderig takig part i a trial you are always free to discuss this decisio with frieds ad relatives or other healthcare providers, icludig your geeral practitioer or a specialist. 14

15 About this iformatio This material was produced by PAPAA. Please be aware that research ad developmet of treatmets are ogoig. Refereces ad sources of evidece for this leaflet are available upo request or ca be foud o our website. For the latest iformatio or ay amedmets to this material please cotact us or visit our website. The site cotais iformatio o treatmets, glossary of terms ad icludes patiet experieces ad case histories. This material was reviewed ad fully revised i 2012 by Dr Amy Foulkes, MRC Cliical Research Fellow based at the Uiversity of Machester. A lay ad peer review pael has provided key feedback o this leaflet. The pael icludes people with or affected by psoriasis ad/or psoriatic arthritis. Published: Jauary 2013 Review date: December 2015 PAPAA The Iformatio Stadard scheme was developed by the Departmet of Health to help the public idetify trustworthy health ad social care iformatio easily. At the heart of the scheme is the stadard itself a set of criteria that defies good quality health or social care iformatio ad the methods eeded to produce it. To achieve the stadard, orgaisatios have to show that their processes ad systems produce iformatio that is: l accurate l evidece-based l impartial l accessible l balaced l well-writte. The assessmet of iformatio producers is provided by idepedet certificatio bodies accredited by The Uited Kigdom Accreditatio Service (UKAS). Orgaisatios that meet The Stadard ca place the quality mark o their iformatio materials ad their website - a reliable symbol of quality ad assurace. 15

16 The charity for people with psoriasis ad psoriatic arthritis PAPAA, the sigle idetity of the Psoriatic Arthropathy Alliace ad the Psoriasis Support Trust. The orgaisatio is idepedetly fuded ad is a pricipal source of iformatio ad educatioal material for people with psoriasis ad psoriatic arthritis i the UK. PAPAA supports both patiets ad professioals by providig material that ca be trusted (evidecebased), which has bee approved ad cotais o bias or agedas. PAPAA provides positive advice that eables people to be ivolved, as they move through their healthcare jourey, i a iformed way which is appropriate for their eeds ad ay chagig circumstaces. Cotact: PAPAA 3 Horseshoe Busiess Park, Lye Lae, Bricket Wood, St Albas, Herts. AL2 3TA Tel: Fax: [email protected] ISBN CT/06/13 Psoriasis ad Psoriatic Arthritis Alliace is a compay limited by guaratee registered i Eglad ad Wales No Registered Charity No Registered office: Acre House, William Road, Lodo, NW1 3ER