***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Pilot studies for phase III trials - which are comparative r and omized trials design ed to provide preliminary evidence on the clinical efficacy of a drug or intervention - are routinely performed in many clinical areas . Also commonly know as " feasibility " or " vanguard " studies , they are design ed to assess the safety of treatment or interventions ; to assess recruitment potential ; to assess the feasibility of international collaboration or coordination for multicentre trials ; to increase clinical experience with the study medication or intervention for the phase III trials . They are the best way to assess feasibility of a large , expensive full-scale study , and in fact are an almost essential pre-requisite . Conducting a pilot prior to the main study can enhance the likelihood of success of the main study and potentially help to avoid doomed main studies . The objective of this paper is to provide a detailed examination of the key aspects of pilot studies for phase III trials including : 1 ) the general reasons for conducting a pilot study ; 2 ) the relationships between pilot studies , proof-of-concept studies , and adaptive design s ; 3 ) the challenges of and misconceptions about pilot studies ; 4 ) the criteria for evaluating the success of a pilot study ; 5 ) frequently asked questions about pilot studies ; 7 ) some ethical aspects related to pilot studies ; and 8) some suggestions on how to report the results of pilot investigations using the CONSORT format Abstract The assessment of clinical ly meaningful changes in  patient‐reported pain  has become increasingly important when interpreting results of clinical studies . However , proposed response criteria , such as the minimal clinical ly important difference , do not correspond with the growing need for information on truly meaningful , individual improvements . The aim of the present study was to investigate satisfactory improvements in pain from the patient ’s perspective . Data were collected in a 2‐week prospect i ve study of 181 arthritis patients treated with a local corticosteroid injection .  Baseline and follow‐up pain were assessed on 100 mm visual analogue scales for pain intensity ( VAS‐PI ) . At baseline , patients also marked a hypothetical level on a VAS‐PI representing a satisfactory improvement in pain . Patient‐perceived satisfactory improvement ( PPSI ) was constructed using a 5‐point categorical rating of change scale at follow‐up as the anchor . PPSI was associated with a minimal reduction of 30 mm or 55 % on the VAS‐PI . Since absolute change in pain associated with satisfactory improvement proved highly dependent on baseline pain , percent change scores performed better in classifying improved patients . The 55 % threshold for satisfactory improvement was consistent over the course of treatment and reasonably consistent across groups of patients . Our data suggest that PPSI is a clinical ly relevant and stable concept for interpreting truly meaningful improvements in pain from the individual perspective In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring  dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials Background Acupuncture is increasingly being used for many conditions including chronic neck pain . However the evidence remains inconclusive , indicating the need for further well- design ed research . The aim of this study was to conduct a pilot r and omised controlled parallel arm trial , to establish key features required for the design and implementation of a large-scale trial on acupuncture for chronic neck pain . Methods Patients whose GPs had diagnosed neck pain were recruited from one general practice , and r and omised to receive usual GP care only , or acupuncture  ( up to 10 treatments over 3 months ) as an adjunctive treatment to usual GP care . The primary outcome measure was the Northwick Park Neck Pain Question naire ( NPQ ) at 3 months . The primary analysis was to determine the sample size for the full scale study . Results Of the 227 patients with neck pain identified from the GP data base , 28 ( 12.3 % ) consenting patients were eligible to participate in the pilot and 24 ( 10.5 % ) were recruited to the trial . Ten patients were r and omised to acupuncture , receiving an average of eight treatments from one of four acupuncturists , and 14 were r and omised to usual GP care alone . The sample size for the full scale trial was calculated from a clinical ly meaningful difference of 5 % on the NPQ and , from this pilot , an adjusted st and ard deviation of 15.3 % . Assuming 90 % power at the 5 % significance level , a sample size of 229 would be required in each arm in a large-scale trial when allowing for a loss to follow-up rate of 14 % . In order to achieve this sample , one would need to identify patients from data bases of GP practice s with a total population of 230,000 patients , or approximately 15 GP practice s roughly equal in size to the one involved in this study ( i.e. 15,694 patients ) . Conclusion This pilot study has allowed a number of recommendations to be made to facilitate the design of a large-scale trial , which in turn will help to clarify the existing evidence base on acupuncture for neck pain Context . The term “ sufficiently important difference ” ( SID ) refers to the overall amount of benefit that people consider sufficient to justify the costs and risks of treatment . Little is known about patient preferences regarding benefits and harms of common cold treatments . Objectives . To develop methods to assess SID and to estimate SID for common cold . Design : The authors conducted in-person and telephone interviews with people with colds , using benefit harm tradeoff methods . The hypothetical benefit of reduction in length of illness was traded off against best estimates of costs and risks . First , the authors briefly described costs , risks , and possible symptomatic benefits of 4 treatment scenarios , based on evidence regarding vitamin C , echinacea , zinc , and pleconaril , an antiviral . Hypothetical benefit ( reduction of illness duration ) was then varied until the cold sufferer indicated that the treatment was minimally desirable . Participants . Interviews were conducted in person with 149 community-recruited adult participants , once at the beginning of their colds , and then again within a few days after symptoms had resolved . Additionally , 162 adult callers with self-identified colds completed interviews via telephone . Results . A total of 460 benefit harm tradeoff interviews ( 1840 treatment scenarios ) estimated overall mean SID as 52.6 h ( 95 % CI , 50.6 to 54.6 ) . For the scenario based on vitamin C , mean SID was estimated as 26.1 h ( 95 % CI , 23.2 to 29.3 ) , with 142 of 460 ( 31 % ) saying they would take it regardless of duration benefit , and 22 of 460 ( 5 % ) saying they would not take it , regardless of duration benefit . For the echinacea-based scenario , mean SID was estimated at 36.8 h ( 33.4 to 40.2 ) , with 105 ( 23 % ) favoring and 41 ( 9 % ) rejecting treatment , regardless of duration benefit . For the zinc lozenge-based scenario , mean SID was estimated as 64.8 h ( 61.0 to 67.9 ) , with 42 ( 9 % ) favoring and 109 ( 24 % ) rejecting treatment . For the prescription antiviral-based scenario , mean SID was estimated as 82.6 h ( 78.7 to 86.7 ) , with 29 ( 6 % ) favoring and 223 ( 48 % ) rejecting . Severity of illness at the time of interview did not appear to significantly influence responses . Possible side effects , treatment type ( tablet v. lozenge v. liquid ) , monetary costs , and opportunity costs ( e.g. , getting to the doctor or pharmacy , dosing frequency ) did appear to be important in influencing these preference patterns . Conclusions . Our study suggests that , on average , people want the duration of their colds to be reduced by between 26 and 65 h to justify potential harms of popular cold treatments . A prescription antiviral would require a greater benefit ( 83 h ) to justify larger perceived risks This study applied a  cost-effectiveness model to seven r and omized trials . The model demonstrates the effect of design choices made in the planning stages of a clinical trial on the costs and benefits derived from conducting the trial . The study focused on one parameter used to calculate sample size : the minimum clinical ly important difference in event rates between control and experimental therapies . The study shows that the model can be operationalized to these trials . A computerized software package and manual has been developed to simplify the calculations . While there was some variation in the incremental cost-effectiveness ratios across the seven trials in this study , all ratios may be below the funding threshold . This analytical technique can be used to demonstrate explicitly the re source consequences of the design of r and omized trials and perhaps to set funding priorities Background Central to the design of a r and omised controlled trial ( RCT ) is a calculation of the number of participants needed . This is typically achieved by specifying a target difference , which enables the trial to identify a difference of a particular magnitude should one exist . Seven methods have been proposed for formally determining what the target difference should be . However , in practice , it may be driven by convenience or some other informal basis . It is unclear how aware the trialist community is of these formal methods or whether they are used . Purpose To determine current practice regarding the specification of the target difference by surveying trialists . Methods Two surveys were conducted : ( 1 ) Members of the Society for Clinical Trials ( SCT ) : participants were invited to complete an online survey through the society ’s email distribution list . Respondents were asked about their awareness , use of , and willingness to recommend methods ; ( 2 ) Leading UK- and Irel and -based trialists : the survey was sent to UK Clinical Research Collaboration registered Clinical Trials Units , Medical Research Council UK Hubs for Trial Methodology Research , and the Research Design Services of the National Institute for Health Research . This survey also included questions about the most recent trial developed by the respondent ’s group . Results Survey 1 : Of the 1182 members on the SCT membership email distribution list , 180 responses were received ( 15 % ) . Awareness of methods ranged from 69 ( 38 % ) for health economic methods to 162 ( 90 % ) for pilot study . Willingness to recommend among those who had used a particular method ranged from 56 % for the opinion-seeking method to 89 % for the review of evidence -base method . Survey 2 : Of the 61 surveys sent out , 34 ( 56 % ) responses were received . Awareness of methods ranged from 33 ( 97 % ) for the review of evidence -base and pilot methods to 14 ( 41 % ) for the distribution method . The highest level of willingness to recommend among users was for the anchor method ( 87 % ) . Based upon the most recent trial , the target difference was usually one viewed as important by a stakeholder group , mostly also viewed as a realistic difference given the interventions under evaluation , and sometimes one that led to an achievable sample size . Limitations The response rates achieved were relatively low despite the surveys being short , well presented , and having utilised reminders . Conclusion Substantial variations in practice exist with awareness , use , and willingness to recommend methods varying substantially . The findings support the view that sample size calculation is a more complex process than would appear to be the case from trial reports and protocol s. Guidance on approaches for sample size estimation may increase both awareness and use of appropriate formal methods To test the impact of nasal dilator strips ( NDSs ) on  insomnia severity , sleep-disordered breathing ( SDB ) symptoms , sleep quality , and quality of life .  R and omized , controlled trial of 4 weeks ' duration . Community sample of nonobese , adults with a primary sleep complaint of chronic sleep-maintenance insomnia and mild to moderate SDB symptoms ( treatment , n=42 ; control , n=38 ) . Primary outcomes were four vali date d scales : Insomnia Severity Index ( ISI ) , Pittsburgh Sleep Quality Index ( PSQI ) , Functional Outcomes of Sleep Question naire ( FOSQ ) , and Quality of Life Enjoyment and Satisfaction Question naire ( QLESQ ) . Secondary outcomes were sleep indices , nonrestorative sleep ratings , and SDB symptoms , assessed retrospectively and prospect ively . Both groups received nonspecific education about sleep disorders . Treatment group also received a brief SDB education and nasal strip instructions . At 4 weeks ' follow-up , the treatment group demonstrated significant ( p=.0001 ) , large improvements in ISI and PSQI ( mean Cohen 's d=1.18 ) and significant ( p<.02 ) , medium-sized improvements in FOSQ and QLESQ ( mean d=0.51 ) compared to small , nonsignificant changes in control group ( Cohen 's d range=0.36–0.09 ) . Treatment group change scores among all four primary variables were significantly correlated ( mean r=0.50 , p=0.01 ) . Secondary prospect i ve and retrospective outcomes showed medium to large improvements in treatment compared to controls for sleep indices ( mean d=0.52 vs 0.28 ) , nonrestorative sleep ratings ( mean d=0.69 vs 0.11 ) , and sleep breathing symptoms ( mean d=0.47 vs 0.09 ) . Significance was obtained for prospect i ve sleep indices ( p=0.01 ) , retrospective , and prospect i ve nonrestorative sleep ratings ( p=0.003 , < 0.05 ) , and 
    Output:
    
CONCLUSIONS A variety of methods are available that research ers can use for specifying the target difference in an RCT sample size calculation .