Joint Arrangements for Research STANDARD OPERATING PROCEDURE R&D SOP 605 Sample Size Calculation Version date Effective date Number of pages Review date Version 1.2 17/07/2014 18/07/2014 5 01/07/2016 Author Role Professor Lee Shepstone Head of Statistics, Norwich CTU Approved by Role Signature Date Rachael Mold Head of NNUH UEA Joint Research Rachael Mold 17th July 2014 Authorised by Role Signature Date Professor Marcus Flather R&D Director Marcus Flather 17th July 2014 R&D SOP 605 v1.2 Effective Date: 18/07/ 2014 Page 1 of 6 Joint Arrangements for Research It is the responsibility of all users of this SOP to ensure that the correct version is being used. All staff should regularly check the NNUH R&D website for information relating to the implementation of new or revised versions of SOPs. Staff must ensure that they are adequately trained in the new procedure and must make sure that all copies of superseded versions are promptly withdrawn from use. The definitive versions of all Joint NNUH/UEA health care research SOPs appear online. If you are reading this in printed form please check that the version number and effective date is the most recent one as shown on the NNUH R&D website. TABLE OF CONTENTS 1 ABBREVIATIONS 3 2 INTRODUCTION 3 3 SCOPE 3 4 PRODUCING SAMPLE SIZE CALCULATIONS 3 5 DOCUMENTATION OF SAMPLE SIZE CALCULATIONS 4 6 RELATED DOCUMENTS 5 7 LIST OF APPENDICES 5 Appendix 1 SOP Change Control and Review Form R&D SOP 605 v1.2 Effective Date: 18/07/ 2014 6 Page 2 of 6 Joint Arrangements for Research 1 ABBREVIATIONS CTIMP CTU GCP ICH NNUH PI R&D SSC REN SOP TMF UEA Clinical Trial of an Investigational Medicinal Product Clinical Trials Unit Good Clinical Practice International Conference for Harmonisation Norfolk and Norwich University Hospital Principal Investigator Research and Development Sample size calculation Research and Enterprise Services UEA Standard Operating Procedure Trial Master File University of East Anglia 2 INTRODUCTION This SOP defines the procedure for the production of Sample Size Calculations (SSC) for clinical trials. Whilst the detailed procedure of this SOP relates to clinical trials, the principles of this SOP should be adopted for non-clinical trials healthcare research by the member(s) of the research team with responsibility for statistical design and analysis. 3 SCOPE This SOP applies to all healthcare research sponsored by NNUH or UEA which falls within the scope of the Research Governance Framework (2nd edition 2005). Where additional legislation applies, for example the Medicines for Human Use (Clinical Trials) Regulations 2004 (and amendments) or the Medical Devices Regulations 2002, required procedures will be indicated. External sponsors may require use of their own SOPs and this will be specified in site agreements. It is the responsibility of the local PI to ensure that study specific SOPs can be operated without conflict to this SOP and in accordance with all organisational polices related to research. 4 PRODUCING SAMPLE SIZE CALCULATIONS A sample size calculation (SSC) should be carried out by an appropriately qualified individual, usually the nominated trial statistician, and using appropriate software. It should be based upon information provided by the trial Chief Investigator and other members of the trial team. R&D SOP 605 v1.2 Effective Date: 18/07/ 2014 Page 3 of 6 Joint Arrangements for Research SSCs should be considered at a very early stage of clinical trial development. They are required for funding and governance applications and need to be justified in detail. It is recognised that there are differing approaches to SSCs depending on trial types and objectives. Generally, an SSC will be based around a degree of precision in a parameter estimate, often involving the notion of statistical Power and statistical significance (or, equivalently, Type II and Type I errors). However, for some studies, such as feasibility or pilot studies, such an approach will not be appropriate but the sample size still needs to be justified on alternative grounds. The basis of the SSC will often be the agreed primary efficacy end-point. Typically, a minimal clinically relevant effect will need to be agreed upon amongst the trial team. Ideally, there should be some justification that this is achievable. An estimate of between group variation will typically be required. The source for this needs to be documented. Statistical errors (Type I and Type II) to be tolerated need to be stated and where ‘not typical’ should be justified. Typical values would be a ‘two-sided’ Type I error of 5% and Type II error of 80% or 90%, preferably the latter. 5 DOCUMENTATION OF SAMPLE SIZE CALCULATIONS It is recognised that there may be a degree of iteration and different versions of SSCs should be documented (SOP 800 Documentation Management). Documentation for SSCs should clearly state: • the date of the calculation, • the individual responsible, • any software used, • the general approach to the calculation, • assumptions made, • values included in the calculation • where possible, references to supporting literature. • Date and individual responsible for independent quality checks (when appropriate see below) Quality When an application is being made for funding a quality check on the SCC should be made prior to the submission for funding. If changes to the sample size are made as a result of peer review during the funding application, an additional quality check should be made prior to the submission for Ethical approval. R&D SOP 605 v1.2 Effective Date: 18/07/ 2014 Page 4 of 6 Joint Arrangements for Research 6 RELATED DOCUMENTS SOP 800 Documentation Management 7 LIST OF APPENDICES Appendix 1: Change Control, Revision and Review Sheet R&D SOP 605 v1.2 Effective Date: 18/07/ 2014 Page 5 of 6 Joint Arrangements for Research Appendix 1: Change Control, Revision and Review Sheet CHANGE CONTROL, REVISION and REVIEW SHEET: SOP 605 Version No 1.1 Change Date 01/04/2014 Reason for Change Extend time scale 1.2 18/07/2014 Minor amendments as part of the bi-annual review including the addition of statistical significance. Reviewer: Designation : Date: A M Swart Director, Norwich CTU 17.06.2014 Reviewer : Designation : Date: Allan Clark Senior Statistician, Norwich CTU 17.06.2014 Reviewer : Designation : Date: R&D SOP 605 v1.2 Effective Date: 18/07/ 2014 Page 6 of 6