1. From data to publication Jonas Ranstam PhD

2. theoryoutcome hypothesis data

3. theory reasoning study designoutcome hypothesisstatistical analysis data collection data

4. reasoning study designstatistical analysis data collection

5. To discuss in this presentationstudy design - observation (case report, survey, epidemiological study) - experiment (phantom, in vitro, in vivo, clinical trial)data collection - registration, monitoring, validation, documentationstatistical analysis - data description, effect estimation, evaluation of bias and uncertaintyreasoning - interpretation of outcome with respect to the limitations imposed by study design, data collection and statistical analysis

6. Design features (simplified)------------------------------------------------------------------------------------------ Design --------------------------------------------------------Characteristics Experimental Observational------------------------------------------------------------------------------------------Studied effects beneficial harmfulSample size small largeFollow up short longInternal validity better worseMain outcome efficacy effectivenessExternal validity worse better------------------------------------------------------------------------------------------

7. Design features (simplified)---------------------------------------------------------------------------------------------------------------------- Design ----------------------------------------------------------------------------------Characteristics Experimental Observational----------------------------------------------------------------------------------------------------------------------Data collection from CRF to database from ? to registerStatistical analysis precision oriented validity orientedReasoning multiplicity, missing data, confounding, selection and compliance, superiority, information bias, measurement non-inferiority errors----------------------------------------------------------------------------------------------------------------------

8. Data collection

9. DIRECTIVE 2001/20/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use4. All clinical trials, including bioavailability and bioequivalence studies, shall be designed, conducted and reported in accordance with the principles of good clinical practice.

10. ICH-GCP1.24 Good Clinical Practice (GCP)A standard for the design, conduct, performance,monitoring, auditing, recording, analyses, and reportingof clinical trials that provides assurance that the dataand reported results are credible and accurate, and thatthe rights integrity and confidentiality of trial subjects areprotected.

11. ICH-GCP4.9 Records and ReportsThe investigator should ensure the accuracy,completeness, legibility, and timeliness of all the datareported to the sponsor in the CRFs and I all requiredreports.

12. ICH-GCP5.5 Trial Management, Data Handling, and RecordKeepingIf data are transformed during processing, it shouldalways be possible to compare the original data andobservations with the processed data.( Audit trail: Documentation that allows reconstruction of the course of events)

13. ICH-GCP1.6 AuditA systematic and independent examination of trialrelated activities and documents to determine whetherth evaluated trial related activities were conducted, andthe data were recorded, analyzed and accuratelyreported according to the protocol, sponsors standardoperating procedures (SOPs), Good Clinical Practice(GCP), and the applicable regulatory requirement(s).

14. Obligation to Register Clinical TrialsThe ICMJE defines a clinical trial as any researchproject that prospectively assigns human subjects tointervention or concurrent comparison or control groupsto study the cause-and-effect relationship between amedical intervention and a health outcome. Medicalinterventions include drugs, surgical procedures,devices, behavioral treatments, process-of-carechanges, and the like.

15. Requirements for observational studiesICMJE - Selection and Description of ParticipantsDescribe your selection of the observational or experimentalparticipants (patients or laboratory animals, includingcontrols) clearly, including eligibility and exclusion criteria anda description of the source population.

16. Requirements for observational studiesThe STROBE statementDescribe the setting, locations, and relevant dates, includingperiods of recruitment, exposure, follow-up, and datacollection.For each variable of interest, give sources of data anddetails of methods of assessment (measurement).

17. Statistical analysis and reasoning

18. Misunderstandings about statistical calculations- They reveal otherwise unknown information about the studied population (sample)- Their purpose is to find statistically significant differences or effects- It is only interesting whether a difference has p