Study group SBS-AE. Version

Transcription

1 Study group SBS-AE a. Dipl.-Psych. Michael Köhler Investigators a. Prof. Dr. med. Thomas Fischer a. Prof. Dr. med. Jörg Frommer, M.A. b. Universitätsklinik für Psychosomatische Medizin und Psychotherapie, Medizinische Fakultät der Otto-von-Guericke-Universität Magdeburg, Universitätsklinikum Magdeburg d. Tel.: , Fax: ; Biometry / Data management a. Dipl.-Psych. Michael Köhler michael.koehler@med.ovgu.de a. Prof. Dr. rer. nat. Siegfried Kropf b. Institut für Biometrie und Medizinische Informatik, Medizinische Fakultät der, d. Tel.: , Fax: ; siegfried.kropf@med.ovgu.de

2 Synopsis Project title Acronym Responsible Clinic analogue GCP-guideline The Somatic Burden Score: Development and validation of a quantitative tool to evaluate the somatic burden due to chemotherapy-induced adverse events SBS-AE Department of Haematology and Oncology, Otto-von-Guericke-University Magdeburg Principal Investigator Approval voting Study sample Study design Inclusion criteria Exclusion criteria Purpose Dipl.-Psych. Michael Köhler A study protocol was approved by the Institutional Review Board of University Hospital Magdeburg. Patients with haematological malignancies and autologous hematopoietic stem cell transplantation (HSCT) following high-dose chemotherapy (HDC) a. Prospective, monocentric, non-interventional design analogue to the state-of-the-art-recommendations for clinical studies according to Faller (2004) b. Follow-up-questionnaire-design with a priori specified hypotheses. It was accomplished as part of an observational study with T1, at beginning of stem cell mobilisation therapy with following separation; T2, at beginning, and T3, at discharge after HDC. c. This study is registered with German Clinical Trials Register (Main ID: DRKS ). a. Acute / chronic haematological malignancy AND / OR b. autologous hematopoietic stem cell transplantation (HSCT) following high-dose chemotherapy (HDC) c. ECOG Performance Status 2 d. 18 years old e. Patients who were able to read and understand a German-language questionnaire f. Patients who were able to cognitive understand diagnosis and treatment g. Patients first autologous HSCT h. written informed consent a. current psychiatric treatment/medication b. use of sedative medication c. ECOG Performance Status > 2 Development, theoretical background, and validation of a new summary tool for evaluation of the somatic burden due to chemotherapy-induced adverse events.

3 Theoretical background The AE-data-concept by Bentzen et al. (2003) Primary objective To determine SBS-AE s criterion validity and construct validity Secondary objectives Instruments Target value Sample size Biometry Publication Descriptive evaluation of: a. Health-related quality of life b. Adverse-event reporting (toxicity): fever, diarrhoea, vomiting, mucositis, and pain c. Somatic burden due to chemotherapy-induced adverse events a. NCI-CTCAE v3.0 b. SF-36 c. PHQ-9 d. General Self-Efficacy Scale e. Basic Documentation for Psycho- Oncology (PO-Bado) a. Weighted, relative duration of an AE grade using CTCAE v3.0 (Grading-SBS) a. Power calculation with G*power both for the primary hypotheses analysis for multiple correlations with k=5 predictors and in order to support secondary analyses resulted in at least 38 participants (R , 80% power, p<0.05). b. For the primary hypotheses analysis for differences an a priori analysis resulted in n 50 required participants (d>0.5, 80% power, p<0.05%). a. The primary analysis comprised the summary scores using the O- SBS-AE, the SF-36 physical health summary-score, and the summarized AE profiles. b. Age was excluded as potentially confounding variable after calculation of correlation between age and variables of primary analysis. c. Criterion validity: Multiple correlations per linear regression analyses d. Convergent validity: e. Discriminant validity: t-tests and analyses of variance (ANOVA) f. A one-sided p value of less than 0.05 was considered to be significant in all analyses. g. Effect sizes were calculated: 1) Effect size for group differences Cohen s d=t[(1/n 1 )+(1/n 2 )] 1/2 ; 2) Effect size for multiple correlation f 2 =R 2 /1-R 2. Concerning coherent use of effect sizes we converted correlation coefficients in Cohen s d using the following formula: d=2r/(1 r 2 ) 1/2 h. A Cohen s d of 0.8 was considered large (f 2 >0.35), 0.5 was considered medium (f 2 >0.15), and 0.2 was considered small (f 2 >0.02) a. According to STROBE checklist

4 The STROBE statement-checklist Quantitative tool to evaluate the somatic burden due to chemotherapy-induced adverse events: the somatic burden score Michael Koehler 1, Thomas Fischer MD 1, Siegfried Kropf MD 2, Joerg Frommer MD 3 1 Department of Haematology and Oncology, Otto-von-Guericke-University Magdeburg, Leipziger Straße 44, Magdeburg, Germany 2 Institute for Biometry and Medical Informatics, Otto-von-Guericke-University Magdeburg, Leipziger Straße 44, Magdeburg, Germany 3 Department of Psychosomatic Medicine and Psychotherapy, Otto-von-Guericke-University Magdeburg, Leipziger Straße 44, Magdeburg, Germany Corresponding author: Michael Koehler Department of Haematology and Oncology Otto-von-Guericke-University Magdeburg Leipziger Straße Magdeburg, Germany address: michael.koehler@med.ovgu.de Tel.: ; Fax:

5 Item Recommendation Reported on manuscript page Title and abstract 1 (a) Indicate the study s design with a commonly used term in the title or the 2 abstract (b) Provide in the abstract an informative and balanced summary of what was 2 done and what was found Introduction Background/ 2 Explain the scientific background and rationale for the investigation being 3, 4 rationale reported Objectives 3 State specific objectives, including any pre-specified hypotheses 4, table 12 Methods Study design 4 Present key elements of study design early in the paper 5 Setting 5 Describe the setting, locations, and relevant dates, including periods of 5, recruitment, exposure, follow-up, and data collection Participants 6 (a) Cohort study give the eligibility criteria, and the sources and methods of 5 selection of participants. Describe methods of follow-up Variables 7 Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers. Give diagnostic criteria, if applicable 5-8 Data sources/ measurement 8 For each variable of interest give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods if there is more than one group Bias 9 Describe any efforts to address potential sources of bias 8-9 Study size 10 Explain how the study size was arrived at 9 Quantitative 11 Explain how quantitative variables were handled in the analyses. If applicable, 8-9 variables describe which groupings were chosen, and why Statistical methods 12 (a) Describe all statistical methods, including those used to control for 8-9 confounding (b) Describe any methods used to examine subgroups and interactions 8-9 (c) Explain how missing data were addressed 8-9 (d) Cohort study if applicable, explain how loss to follow-up was addressed - (e) Describe any sensitivity analyses - Results Participants 13 (a) Report the numbers of individuals at each stage of the study eg, numbers 10 potentially eligible, examined for eligibility, confirmed eligible, included in the study, completing follow-up, and analysed (b) Give reasons for non-participation at each stage 10 (c) Consider use of a flow diagram - Descriptive data 14 (a) Give characteristics of study participants (eg, demographic, clinical, social) table 2 and information on exposures and potential confounders (b) Indicate the number of participants with missing data for each variable of 10 interest (c) Cohort study summarise follow-up time (eg, average and total amount) - Outcome data 15 Cohort study report numbers of outcome events or summary measures over time 10, table 3-6 Main results 16 (a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates - and their precision (eg, 95% confidence interval). Make clear which confounders were adjusted for and why they were included (b) Report category boundaries when continuous variables were categorised - (c) If relevant, consider translating estimates of relative risk into absolute risk for - a meaningful time period Other analyses 17 Report other analyses done eg, analyses of subgroups and interactions, and sensitivity analyses 11 table 7-11 Discussion Key results 18 Summarise key results with reference to study objectives 12 table 12 Limitations 19 Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss both direction and magnitude of any potential bias Interpretation 20 Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other 13, table 13 relevant evidence Generalizability 21 Discuss the generalizability (external validity) of the study results Other information Funding 22 Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based 9 5-8