time needed to collect and analyse data.



From this document you will learn the answers to the following questions:

What is necessary for the ability to recruit patients?

What data is available for Phase II trials?

When key elements are feasible , what is it?

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Transcription:

Feasibility and Pilt studies This is a definitin that has been agreed by the Efficacy and Mechanism Evaluatin (EME), Public Health Research (PHR), Health Technlgy Assessment (HTA) and Research fr Patient Benefit (RfPB) Prgrammes. We expect that when pilt r feasibility studies are prpsed by applicants, r specified in cmmissining briefs, a clear rute f prgressin criteria t the substantive study will be described. Listing clear prgressin criteria will apply whether the brief r prpsal describes just the preliminary study r bth tgether. Whether preliminary and main studies are funded tgether r separately may be decided n practical grunds. Feasibility studies Feasibility Studies are pieces f research dne befre a main study in rder t answer the questin Can this study be dne?. They are used t estimate imprtant parameters that are needed t design the main study. Fr instance: standard deviatin f the utcme measure, which is needed in sme cases t estimate sample size; willingness f participants t be randmised; willingness f clinicians t recruit participants; number f eligible patients; carers r ther apprpriate participants; characteristics f the prpsed utcme measure and in sme cases feasibility studies might invlve designing a suitable utcme measure; fllw-up rates, respnse rates t questinnaires, adherence/cmpliance rates, ICCs in cluster trials, etc. availability f data needed r the usefulness and limitatins f a particular database; and time needed t cllect and analyse data. Feasibility studies fr randmised cntrlled trials may nt themselves be randmised. Crucially, feasibility studies d nt evaluate the utcme f interest; that is left t the main study. If a feasibility study is a small randmised cntrlled trial, it need nt have a primary utcme and the usual srt f pwer calculatin is nt nrmally undertaken. Instead the sample size shuld be adequate t estimate the critical parameters (e.g. recruitment rate) t the necessary degree f precisin.

Pilt studies Pilt studies are a versin f the main study that is run in miniature t test whether the cmpnents f the main study can all wrk tgether. It is fcused n the prcesses f the main study, fr example t ensure recruitment, randmisatin, treatment, and fllw-up assessments all run smthly. It will therefre resemble the main study in many respects, including an assessment f the primary utcme. In sme cases this will be the first phase f the substantive study and data frm the pilt phase may cntribute t the final analysis; this can be referred t as an internal pilt. Or at the end f the pilt study the data may be analysed and set aside, a s-called external pilt. Feasibility and pilt studies: which prgramme shuld I apply t? There are a number f NIHR prgrammes which will fund feasibility and pilt studies. There are n strict rules abut which prgramme funds which feasibility r pilt study and it is fr applicants t chse the mst apprpriate in the cntext f the guidance n applicability prvided n the webpages fr each prgramme. Nevertheless, in chsing yu might like t cnsider the fllwing: 1. Is the prgramme apprpriate in terms f gegraphy and grant size (RfPB funding, fr example, can nly be accessed thrugh NHS bdies and ther prviders f NHS services in England and has a maximum grant size f 350,000)? 2. Can a rbust case be made fr the plausibility f the interventin and clinical imprtance f any subsequent full trial? If there is gd prf f cncept and/r efficacy data available and there is a clear plan t explre the interventin further in a large clinical trial, then HTA r EME might be cnsidered the latter in particular if there are substantial mechanistic elements and labratry supprt invlved in the prject. On the ther hand, if the feasibility r pilt study is fr a ptential trial which might be viewed as mre speculative, with n clear plan fr a large trial in the very near future, r in which there seems a high risk that the pilt/feasibility study is likely t demnstrate that a full trial is nt pssible, then the smaller sums that RfPB prvide might be seen as mre apprpriate. Nte that feasibility and pilt studies shuld be distinguished frm Phase II trials, in which sme srt f evidence fr efficacy, ften in a surrgate marker, is sught prir t embarking n a full Phase III trial: EME might be the mst apprpriate funding stream fr these if there

is strng scientific interest in the questin, and RfPB if there is a clear ptential trajectry int patient benefit. The PHR Prgramme als funds feasibility and pilt studies within its remit f evaluating public health interventins delivered utside the NHS.

RfPB Guidance n applying fr feasibility studies Clinical trials are expensive and the chances f successful cmpletin are imprved if it can be shwn befrehand that key elements (such as the ability t recruit patients) are feasible befre the main study starts. The RfPB Prgramme will therefre fund such feasibility studies which are investigatins carried ut befre a main study in rder t answer the questin Can this study be dne?. The research plan fr a feasibility study shuld therefre cntain a brief utline f the prpsed main study and a list f the uncertain imprtant parameters that that are needed t design the main study, as described belw. The Research Plan sectin f the applicatin frm shuld include: 1. A brief utline f the intended main trial. Sme f these details will f curse depend n the results f the prpsed feasibility research but a key part f evaluating the value f a feasibility study is whether r nt a full trial is likely t get funded. Yu shuld therefre briefly describe as far as yu can what the main trial wuld lk like. This might include (if they are knwn), whether an individual patient randmised r cluster trial, the number f arms, the inclusin criteria, the nature f the interventin and f the cmparatr in the cntrl grup, the primary endpint, and the pssible range f clinical sites frm which patients wuld be recruited. 2. A list f the parameters which the feasibility study intends t clarify r estimate. These may include: the number f eligible patients, carers r ther apprpriate participants; an explratin f different methds f identifying/recruiting patients; the willingness f clinicians t recruit and randmise participants; the willingness f participants t be randmised; the practicality f delivering the interventin(s) in the prpsed setting(s); variatin in use r delivery f the interventin in each setting; acceptability f the interventin t the users; standard deviatin f the utcme measure, which is needed in sme cases t estimate sample size; fllw-up rates, respnse rates t questinnaires, adherence/cmpliance rates, ICCs in cluster trials, etc; availability f data needed r the usefulness and limitatins f a particular database; the time needed t cllect and analyse data;

explring the pprtunities fr PPI (patient and public invlvement) in the research design and its subsequent cnduct. In effect the research plan shuld describe which parameters are t be estimated and hw these will be investigated. 3. A feasibility study des nt necessarily need t include the fllwing: a randmised design: the design will be determined by hw it is prpsed t reduce the uncertainty in the parameters described abve an evaluatin f the utcme f interest: that is left t the main study a primary utcme: if a feasibility study invlves carrying ut a small randmised cntrlled trial it is fr the purpse f evaluating/testing trial prcesses nt the interventin the usual srt f pwer calculatin: the sample size shuld be adequate t estimate the critical parameters (e.g. recruitment rate) t the necessary degree f precisin 3. 1) Lancaster GA, Ddd S, Williamsn PR. Design and analysis f pilt studies: recmmendatins fr gd practice. J Eval Clin Pract 2004, 10:307-12. 2) Arain M, Campbell MJ, Cper CL, Lancaster GA. What is a pilt r feasibility study? A review f current practice and editrial plicy. BMC Medical Research Methdlgy 2010, 10:67. 3) Julius SA. Sample size f 12 per grup rule f thumb fr a pilt study. Pharmaceutical Statistics 2005, 4:287 291.