human
***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 Feasibility and pilot studies play an important role in the preliminary planning of a proposed full-size r and omized clinical trial  ( RCT ) . In essence , feasibility studies are used to help develop trial interventions or outcome measures , whereas pilot studies replicate , in miniature , a planned full-size RCT . However , the terms used for these preliminary studies are sometimes considered synonymous , and in practice may overlap considerably or be combined . The important issue is not the distinction between these : the important distinction is between such preliminary studies and a proper RCT . J Orthop Sports Phys Ther 2014;44(8):555–558 . Many factors can affect the successful implementation and validity of intervention studies . A primary purpose of feasibility and pilot studies is to assess the potential for successful implementation of the proposed main intervention studies and to reduce threats to the validity of these studies . This article describes a typology to guide the aims of feasibility and pilot studies design ed to support the development of r and omized controlled trials and provides an example of the studies underlying the development of one rehabilitation trial . The purpose of most feasibility and pilot studies should be to describe information and evidence related to the successful implementation and validity of a planned main trial . Null hypothesis significance testing is not appropriate for these studies unless the sample size is properly powered . The primary tests of the intervention effectiveness hypotheses should occur in the main study , not in the studies that are serving as feasibility or pilot studies BACKGROUND People with Multiple Sclerosis ( PwMS ) are less physically active than the general population and pragmatic approaches design ed to equip them with the skills and confidence to participate in long-term physical activity are required . OBJECTIVE The objective of this study was to determine the feasibility of a pragmatic exercise intervention in PwMS . METHODS A voluntary sample of 30 PwMS ( male n = 4 , female n = 26 ; mean age = 40 years ; range = 24 - 49 years ) , with mild to moderate disability ( EDSS ≤ 5.5 ) , were recruited from eligible participants attending outpatient clinics . A total of 28 participants were r and omised to a 10 week pragmatic exercise intervention ( 2 × supervised and 1 × home-based session per week ) or usual care . Clinical , functional and quality of life ( MSQoL-54 ) outcomes were assessed at baseline , immediately and 3 months after the intervention . RESULTS Attrition was low ( 2 participants lost to immediate follow-up and 4 participants lost to 3 month follow-up ) , with high compliance rates ( > 75 % of all sessions ) . The intervention group achieved progression of exercise volume ( 24.3 ± 7.0 to 30.9 ± 5.5 min per session ) , intensity ( 60.4 ± 8.8 to 67.7 ± 6.9 % HR max ) and training impulse ( min × average HR = training impulse/load [ arbitrary units ; AU ] ) ( 2600 ± 1105 to 3210 ± 1269AU ) during the intervention , whilst significantly increasing(P = 0.050 ) their physical composite score ( MSQOL-54 ) at 10 weeks and readiness to exercise ( P = 0.003 ) at 3 months compared with usual care . CONCLUSION This pragmatic intervention was feasible for PwMS , but further research is needed to assess its long-term impact on physical activity behaviour Background The success of a clinical trial is often dependant on whether recruitment targets can be met in the required time frame . Despite an increase in research into the benefits of exercise in people with multiple sclerosis ( PwMS ) , no trial has reported detailed data on effective recruitment strategies for large-scale r and omised controlled trials . The main purpose of this report is to provide a detailed outline of recruitment strategies , rates and estimated costs in the Exercise Intervention for Multiple Sclerosis ( ExIMS ) trial to identify best practice s for future trials involving multiple sclerosis ( MS ) patient recruitment . Methods The ExIMS research ers recruited 120 PwMS to participate in a 12-week exercise intervention .  Participants were r and omly allocated to either  exercise or usual-care control groups . Participants were sedentary , aged 18–65 years and had Exp and ed Disability Status Scale scores of 1.0–6.5 . Recruitment strategies included attendance at MS outpatient clinics , consultant mail-out and trial awareness-raising activities . Results A total of 120 participants were recruited over the course of 34 months . To achieve this target , 369 potentially eligible and interested participants were identified . A total of 60 % of participants were recruited via MS clinics , 29.2 % from consultant mail-outs and 10.8 % through trial awareness . The r and omisation yields were 33.2 % , 31.0 % and 68.4 % for MS clinic , consultant mail-outs and trial awareness strategies , respectively . The main reason for in eligibility was being too active ( 69.2 % ) , whilst for eligible participants the most common reason for non-participation was the need to travel to the study site ( 15.8 % ) . Recruitment via consultant mail-out was the most cost-effective strategy , with MS clinics being the most time-consuming and most costly . Conclusions To reach recruitment targets in a timely fashion , a variety of methods were employed . Although consultant mail-outs were the most cost-effective recruitment strategy , use of this method alone would not have allowed us to obtain the predetermined number of participants in the required time period , thus leading to costly extensions of the project or failure to reach the number of participants required for sufficient statistical power . Thus , a multifaceted approach to recruitment is recommended for future trials . Trial registration International St and ard R and omised Controlled Trial Registry number : IS RCT N41541516 ; date registered : 5 February 2009 The Guidelines for Exercise in Multiple Sclerosis ( GEMS ) program is a r and omized controlled trial ( RCT ) examining the feasibility and efficacy of a home-based exercise training program based on recent physical activity guidelines and principles of behavior change for improving symptoms and health-related quality of life ( HRQOL ) in adults with multiple sclerosis ( MS ) . The primary aim is to assess program feasibility in the four domains of process ( e.g. , recruitment , retention , and adherence ) , re sources ( e.g. , communication , staff requirements , and monetary costs ) , management ( e.g. , time and accuracy in data collection /entry , and reporting of adverse events ) and scientific outcomes ( e.g. , safety , burden , participant feedback and efficacy/ outcomes ) . The trial will recruit individuals with mild-to-moderate MS-related disability across the United States who will be r and omized into intervention or waitlist control conditions . All participants will complete home-based assessment s ( including wearing an accelerometer for 7 days and completion of a question naire booklet ) prior to and upon completion of the 4-month program . Participants in the intervention will receive a 4-month home-based exercise program emphasizing aerobic and resistance training . Participants will be provided with exercise equipment , a DVD , a manual and a log-book . The exercise program will be supplemented with periodic newsletters in the mail highlighting principles of behavior change , and video-chats with an exercise specialist to provide motivation and social accountability . This trial serves to inform development of Phase II and III RCTs which can determine the actual efficacy and effectiveness of home-based exercise based on the MS-specific physical activity guidelines for improving symptoms and HRQOL We describe a framework for defining  pilot and feasibility studies  focusing on studies conducted in preparation for a r and omised controlled trial . To develop the framework , we undertook a Delphi survey ; ran an open meeting at a trial methodology conference ; conducted a review of definitions outside the health research context ; consulted experts at an international consensus meeting ; and review ed 27 empirical pilot or feasibility studies . We initially adopted mutually exclusive definitions of pilot and feasibility studies . However , some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions . Their viewpoint was supported by definitions outside the health research context , the use of the terms ‘ pilot ’ and ‘ feasibility ’ in the literature , and participants at the international consensus meeting . In our framework , pilot studies are a subset of feasibility studies , rather than the two being mutually exclusive . A feasibility study asks whether something can be done , should we proceed with it , and if so , how . A pilot study asks the same questions but also has a specific design feature : in a pilot study a future study , or part of a future study , is conducted on a smaller scale . We suggest that to facilitate their identification , these studies should be clearly identified using the terms ‘ feasibility ’ or ‘ pilot ’ as appropriate . This should include feasibility studies that are largely qualitative ; we found these difficult to identify in electronic search es because research ers rarely used the term ‘ feasibility ’ in the title or abstract of such studies . Investigators should also report appropriate objectives and methods related to feasibility ; and give clear confirmation that their study is in preparation for a future r and omised controlled trial design ed to assess the effect of an intervention Purpose : Participation in physical activity for people with Multiple sclerosis ( MS ) is important but can be difficult to sustain long-term . Facilitators for long-term adherence include choice over activity and control over level of engagement , coupled with support , advice and encouragement from a physiotherapist . This is the basis of Blue Prescription , a novel physiotherapy approach aim ed at optimising long-term adherence with physical activity . We evaluated the feasibility and short-term benefits of Blue Prescription in people with MS . Methods : Twenty-seven people with MS ( mean age : 51 ± 11 years , with a range of MS type and disability ) were assessed at baseline and immediately post-intervention with the MS Impact Scale , MS Self-efficacy Scale , and European Quality of Life Question naire . Change in outcomes were analysed with Wilcoxon signed ranks tests . Results : All participants , irrespective of level of disability , were able to choose a physical activity and to engage in it . The physical component MS Impact Scale score significantly improved by a median change of 6.5 ( 95 % CI = −10.5 to −2.0 ; p = 0.007 ; effect size = 0.38 ) . There were no other significant changes in outcomes . Conclusion : Blue Prescription appears feasible and potentially beneficial , particularly in reducing the negative impacts of MS upon individuals , and thus warrants further evaluation . Implication s for Rehabilitation Facilitators for long-term adherence for disabled people include choice over activity and control over level of engagement , coupled with support , advice and encouragement from a physiotherapist . Blue Prescription is a physiotherapy approach aim ed at optimising long-term adherence with physical activity for people with multiple sclerosis . Blue Prescription appears to reduce the negative impacts of multiple sclerosis upon individuals BACKGROUND AND PURPOSE Balance and mobility impairments are common in persons with multiple sclerosis ( MS ) . The primary purpose of this pilot program was to evaluate the feasibility and the effects of group kickboxing on balance and mobility in individuals with MS . METHODS Four individuals with relapsing-remitting or secondary progressive MS participated in a group kickboxing program two times per week for 8 weeks . Outcome measures included the Berg Balance Scale ( BBS ) , Dynamic Gait Index ( DGI ) , Timed Up and Go ( TUG ) , walking speed and the Activities Specific Balance Confidence Scale ( ABC ) . RESULTS Following training , 3 of 4 participants had improvements in BBS performance . All participants demonstrated improvements in the DGI . Changes in the TUG , ABC , and walking speed were more variable . CONCLUSION Group kickboxing appears to be a feasible exercise activity for individuals with MS and may lead to improvement in select measures of balance . Further investigation may be warranted The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement is a guideline design ed to improve the transparency and quality of the reporting of r and omised controlled trials ( RCTs ) . In this article we present an extension to that statement for r and omised pilot and feasibility trials conducted in advance of a future definitive RCT . The checklist applies to any r and omised study in which a future definitive RCT , or part of it , is conducted on a smaller scale , regardless of its design ( eg , cluster , factorial , crossover ) or the terms used by authors to describe the study ( eg , pilot , feasibility , trial , study ) . The extension does not directly apply to internal pilot studies built into the design of a main trial , non-r and omised pilot and feasibility studies , or phase II studies , but these studies all have some similarities to r and omised pilot and feasibility studies and so many of the 
    Output:
    
agent
Our case study successfully enabled us to address the four feasibility metrics , and we provide new information on management feasibility ( i.e. estimate data completeness and estimate data entry ) and scientific outcomes feasibility ( i.e. determining data collection material s appropriateness ) .
Conclusion Our review highlights the existing research and provides a case study which assesses important metrics of study feasibility .
***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 Feasibility and pilot studies play an important role in the preliminary planning of a proposed full-size r and omized clinical trial  ( RCT ) . In essence , feasibility studies are used to help develop trial interventions or outcome measures , whereas pilot studies replicate , in miniature , a planned full-size RCT . However , the terms used for these preliminary studies are sometimes considered synonymous , and in practice may overlap considerably or be combined . The important issue is not the distinction between these : the important distinction is between such preliminary studies and a proper RCT . J Orthop Sports Phys Ther 2014;44(8):555–558 . Many factors can affect the successful implementation and validity of intervention studies . A primary purpose of feasibility and pilot studies is to assess the potential for successful implementation of the proposed main intervention studies and to reduce threats to the validity of these studies . This article describes a typology to guide the aims of feasibility and pilot studies design ed to support the development of r and omized controlled trials and provides an example of the studies underlying the development of one rehabilitation trial . The purpose of most feasibility and pilot studies should be to describe information and evidence related to the successful implementation and validity of a planned main trial . Null hypothesis significance testing is not appropriate for these studies unless the sample size is properly powered . The primary tests of the intervention effectiveness hypotheses should occur in the main study , not in the studies that are serving as feasibility or pilot studies BACKGROUND People with Multiple Sclerosis ( PwMS ) are less physically active than the general population and pragmatic approaches design ed to equip them with the skills and confidence to participate in long-term physical activity are required . OBJECTIVE The objective of this study was to determine the feasibility of a pragmatic exercise intervention in PwMS . METHODS A voluntary sample of 30 PwMS ( male n = 4 , female n = 26 ; mean age = 40 years ; range = 24 - 49 years ) , with mild to moderate disability ( EDSS ≤ 5.5 ) , were recruited from eligible participants attending outpatient clinics . A total of 28 participants were r and omised to a 10 week pragmatic exercise intervention ( 2 × supervised and 1 × home-based session per week ) or usual care . Clinical , functional and quality of life ( MSQoL-54 ) outcomes were assessed at baseline , immediately and 3 months after the intervention . RESULTS Attrition was low ( 2 participants lost to immediate follow-up and 4 participants lost to 3 month follow-up ) , with high compliance rates ( > 75 % of all sessions ) . The intervention group achieved progression of exercise volume ( 24.3 ± 7.0 to 30.9 ± 5.5 min per session ) , intensity ( 60.4 ± 8.8 to 67.7 ± 6.9 % HR max ) and training impulse ( min × average HR = training impulse/load [ arbitrary units ; AU ] ) ( 2600 ± 1105 to 3210 ± 1269AU ) during the intervention , whilst significantly increasing(P = 0.050 ) their physical composite score ( MSQOL-54 ) at 10 weeks and readiness to exercise ( P = 0.003 ) at 3 months compared with usual care . CONCLUSION This pragmatic intervention was feasible for PwMS , but further research is needed to assess its long-term impact on physical activity behaviour Background The success of a clinical trial is often dependant on whether recruitment targets can be met in the required time frame . Despite an increase in research into the benefits of exercise in people with multiple sclerosis ( PwMS ) , no trial has reported detailed data on effective recruitment strategies for large-scale r and omised controlled trials . The main purpose of this report is to provide a detailed outline of recruitment strategies , rates and estimated costs in the Exercise Intervention for Multiple Sclerosis ( ExIMS ) trial to identify best practice s for future trials involving multiple sclerosis ( MS ) patient recruitment . Methods The ExIMS research ers recruited 120 PwMS to participate in a 12-week exercise intervention .  Participants were r and omly allocated to either  exercise or usual-care control groups . Participants were sedentary , aged 18–65 years and had Exp and ed Disability Status Scale scores of 1.0–6.5 . Recruitment strategies included attendance at MS outpatient clinics , consultant mail-out and trial awareness-raising activities . Results A total of 120 participants were recruited over the course of 34 months . To achieve this target , 369 potentially eligible and interested participants were identified . A total of 60 % of participants were recruited via MS clinics , 29.2 % from consultant mail-outs and 10.8 % through trial awareness . The r and omisation yields were 33.2 % , 31.0 % and 68.4 % for MS clinic , consultant mail-outs and trial awareness strategies , respectively . The main reason for in eligibility was being too active ( 69.2 % ) , whilst for eligible participants the most common reason for non-participation was the need to travel to the study site ( 15.8 % ) . Recruitment via consultant mail-out was the most cost-effective strategy , with MS clinics being the most time-consuming and most costly . Conclusions To reach recruitment targets in a timely fashion , a variety of methods were employed . Although consultant mail-outs were the most cost-effective recruitment strategy , use of this method alone would not have allowed us to obtain the predetermined number of participants in the required time period , thus leading to costly extensions of the project or failure to reach the number of participants required for sufficient statistical power . Thus , a multifaceted approach to recruitment is recommended for future trials . Trial registration International St and ard R and omised Controlled Trial Registry number : IS RCT N41541516 ; date registered : 5 February 2009 The Guidelines for Exercise in Multiple Sclerosis ( GEMS ) program is a r and omized controlled trial ( RCT ) examining the feasibility and efficacy of a home-based exercise training program based on recent physical activity guidelines and principles of behavior change for improving symptoms and health-related quality of life ( HRQOL ) in adults with multiple sclerosis ( MS ) . The primary aim is to assess program feasibility in the four domains of process ( e.g. , recruitment , retention , and adherence ) , re sources ( e.g. , communication , staff requirements , and monetary costs ) , management ( e.g. , time and accuracy in data collection /entry , and reporting of adverse events ) and scientific outcomes ( e.g. , safety , burden , participant feedback and efficacy/ outcomes ) . The trial will recruit individuals with mild-to-moderate MS-related disability across the United States who will be r and omized into intervention or waitlist control conditions . All participants will complete home-based assessment s ( including wearing an accelerometer for 7 days and completion of a question naire booklet ) prior to and upon completion of the 4-month program . Participants in the intervention will receive a 4-month home-based exercise program emphasizing aerobic and resistance training . Participants will be provided with exercise equipment , a DVD , a manual and a log-book . The exercise program will be supplemented with periodic newsletters in the mail highlighting principles of behavior change , and video-chats with an exercise specialist to provide motivation and social accountability . This trial serves to inform development of Phase II and III RCTs which can determine the actual efficacy and effectiveness of home-based exercise based on the MS-specific physical activity guidelines for improving symptoms and HRQOL We describe a framework for defining  pilot and feasibility studies  focusing on studies conducted in preparation for a r and omised controlled trial . To develop the framework , we undertook a Delphi survey ; ran an open meeting at a trial methodology conference ; conducted a review of definitions outside the health research context ; consulted experts at an international consensus meeting ; and review ed 27 empirical pilot or feasibility studies . We initially adopted mutually exclusive definitions of pilot and feasibility studies . However , some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions . Their viewpoint was supported by definitions outside the health research context , the use of the terms ‘ pilot ’ and ‘ feasibility ’ in the literature , and participants at the international consensus meeting . In our framework , pilot studies are a subset of feasibility studies , rather than the two being mutually exclusive . A feasibility study asks whether something can be done , should we proceed with it , and if so , how . A pilot study asks the same questions but also has a specific design feature : in a pilot study a future study , or part of a future study , is conducted on a smaller scale . We suggest that to facilitate their identification , these studies should be clearly identified using the terms ‘ feasibility ’ or ‘ pilot ’ as appropriate . This should include feasibility studies that are largely qualitative ; we found these difficult to identify in electronic search es because research ers rarely used the term ‘ feasibility ’ in the title or abstract of such studies . Investigators should also report appropriate objectives and methods related to feasibility ; and give clear confirmation that their study is in preparation for a future r and omised controlled trial design ed to assess the effect of an intervention Purpose : Participation in physical activity for people with Multiple sclerosis ( MS ) is important but can be difficult to sustain long-term . Facilitators for long-term adherence include choice over activity and control over level of engagement , coupled with support , advice and encouragement from a physiotherapist . This is the basis of Blue Prescription , a novel physiotherapy approach aim ed at optimising long-term adherence with physical activity . We evaluated the feasibility and short-term benefits of Blue Prescription in people with MS . Methods : Twenty-seven people with MS ( mean age : 51 ± 11 years , with a range of MS type and disability ) were assessed at baseline and immediately post-intervention with the MS Impact Scale , MS Self-efficacy Scale , and European Quality of Life Question naire . Change in outcomes were analysed with Wilcoxon signed ranks tests . Results : All participants , irrespective of level of disability , were able to choose a physical activity and to engage in it . The physical component MS Impact Scale score significantly improved by a median change of 6.5 ( 95 % CI = −10.5 to −2.0 ; p = 0.007 ; effect size = 0.38 ) . There were no other significant changes in outcomes . Conclusion : Blue Prescription appears feasible and potentially beneficial , particularly in reducing the negative impacts of MS upon individuals , and thus warrants further evaluation . Implication s for Rehabilitation Facilitators for long-term adherence for disabled people include choice over activity and control over level of engagement , coupled with support , advice and encouragement from a physiotherapist . Blue Prescription is a physiotherapy approach aim ed at optimising long-term adherence with physical activity for people with multiple sclerosis . Blue Prescription appears to reduce the negative impacts of multiple sclerosis upon individuals BACKGROUND AND PURPOSE Balance and mobility impairments are common in persons with multiple sclerosis ( MS ) . The primary purpose of this pilot program was to evaluate the feasibility and the effects of group kickboxing on balance and mobility in individuals with MS . METHODS Four individuals with relapsing-remitting or secondary progressive MS participated in a group kickboxing program two times per week for 8 weeks . Outcome measures included the Berg Balance Scale ( BBS ) , Dynamic Gait Index ( DGI ) , Timed Up and Go ( TUG ) , walking speed and the Activities Specific Balance Confidence Scale ( ABC ) . RESULTS Following training , 3 of 4 participants had improvements in BBS performance . All participants demonstrated improvements in the DGI . Changes in the TUG , ABC , and walking speed were more variable . CONCLUSION Group kickboxing appears to be a feasible exercise activity for individuals with MS and may lead to improvement in select measures of balance . Further investigation may be warranted The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement is a guideline design ed to improve the transparency and quality of the reporting of r and omised controlled trials ( RCTs ) . In this article we present an extension to that statement for r and omised pilot and feasibility trials conducted in advance of a future definitive RCT . The checklist applies to any r and omised study in which a future definitive RCT , or part of it , is conducted on a smaller scale , regardless of its design ( eg , cluster , factorial , crossover ) or the terms used by authors to describe the study ( eg , pilot , feasibility , trial , study ) . The extension does not directly apply to internal pilot studies built into the design of a main trial , non-r and omised pilot and feasibility studies , or phase II studies , but these studies all have some similarities to r and omised pilot and feasibility studies and so many of the 
    Output:
    