EVIDENCEFOR DECISION MAKING IN HEALTH CAREJAHRESBERICHT 2012

Basel Institute cebfor Clinical Epidemiology and Biostatistics

EVIDENCEFOR DECISION MAKINGIN HEALTH CAREANNUAL REPORT 2014

EVIDENCEFOR DECISION MAKINGIN HEALTH CAREANNUAL REPORT 2018

4 Foreword of the President of the Board of Trustees 6 Basel Institute for Clinical Epidemiology and Biostatistics (CEB)8 Research Highlights of CEB in 201810 Impact of research from CEB 11 CEB Research12 CEB Teaching 12 CEB Consulting13 Health Technology Assessment (HTA)13 Swiss Transplant Cohort Study 15 Publications of CEB in 201815 Original Publications in Peer Reviewed Journals 21 Editorials, Research Letters, Letters and Non-Peer Reviewed Publications21 Book Chapters21 Presentations24 Posters and Abstracts26 Accomplished Projects in 201826 HIV Infection, Swiss HIV Cohort Study and Multicohort Projects26 Methodological Research Projects29 Anesthesiology29 HTA Reports30 Ongoing Projects in 201830 HIV Infection, Swiss HIV Cohort Study and Multicohort Projects31 Methodological Research Projects33 Oncology34 Anesthesiology34 HTA Reports35 Teaching35 Undergraduate35 Postgraduate36 Supervision of Master Theses36 Supervision of MD Theses36 PhD Students (Epidemiology)38 Staff as of December 31, 2018

CONTENTS

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Dear reader

The board of trustees of the foundation is delighted to present the annual report 2018. The BaselInstitute for Clinical Epidemiology and Biostatistics (CEB) has again been able to achieve a remark -able output of publications, many of them resulting from national and international collaborations.

Let me just highlight two publications: Many of us have been suffering from prolonged tediouscough following a respiratory infection and might have used remedies in the hope for some reliefand better sleep. In a meta-analysis of randomized controlled trials, researchers from CEB havefound for none of currently used treatments good evidence that they provide relevant benefit;this highlights the need for better research for common conditions. For the first time in Switzerland,researchers from CEB have linked by privacy-preserving probability matching long-term cohortdata with insurance claims data to investigate the economic burden of co-morbidity in HIV infection. They were able to characterise the financial consequences of co-morbidity and the implications for long-term care. Such data is indispensable in the current political discussion onhealth care expenditures in Switzerland.

We are proud about CEB’s teaching engagement, in particular within the new bachelor programin medicine at ETH Zurich. We hope this will create synergies and stimulate a new generation ofmedical students with high competences in clinical research methodology.

The achievements of the small team of CEB are a strong motivation to continue our financial engagement for the institute. This team under the lead of Prof. Bucher deserves our full support.

Reto Guetg MDPresident of the Board of Trustees Foundation Institute for Clinical Epidemiology

FOREWORD OF THE PRESIDENT OF THE BOARD OF TRUSTEES

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The Board of TrusteesStefan Kaufmann lic. rer. pol., Prof. Jörg D. Leuppi MD, PhD, Reto Guetg MD

OUR MISSION IS TO IMPROVE DECISION MAKING IN HEALTH CAREWe generate and appraise evidence of medical interventions by own research and evidence synthesis. We use innovative analytical techniques to investigate how new interventions perform in a realworld setting. We invest in clinical research methodology development to improve the quality of clinical research.

OUR STRATEGYWe evaluate whether new or established interventions and technologies improve in the real worldsetting patient relevant outcomes, are safe and represent benefit for the health care system.

RESEARCH & CONSULTINGCEB combines excellence in research and clinical expertise with an extensive consulting activity –a unique distinction from other academic institutions. Services offered range from consulting inclinical trial design to large-scale observational and clinical trial data analysis, individual patientdata, network and standard meta-analyses, Health Technology Assessments and methodologicalsupport for clinical researchers, governmental agencies, health insurers, and industry.

TEACHINGWe teach principles of evidence-based medicine and research methodology to medical studentsat University of Basel and ETH Zurich.

BASEL INSTITUTE FOR CLINICAL EPIDEMIOLOGY AND BIOSTATISTICS (CEB)

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Improve patient outcomes by evidence-based decision making and implementation of efficacious interventionsinto clinical care

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The team of CEB

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RESEARCH HIGHLIGHTS OF CEB IN 2018

Treatments for subacute cough in primary care: Systematic review and meta-analysis of randomized controlledtrials. Speich B et al. Br. J Gen Pract 2018 Oct: 68(675):e694-e702. Background: Subacute cough of 3-8 weeks following a non-specific infection is common but there is no systematicevidence on the many treatment options. Method and results: A systematic overview and meta-analysis was done on treatment options and outcomes in patients with subacute cough. Six randomized controlled in 724 patients assessed montelukast, salbutamol plus ipratropium bromide, gelatine, fluticasone propionate, budesonide, and nociception opioid 1 receptor agonist andcodeine, but no clear benefit on cough recovery or other patient-relevant outcomes of any substance at 14 days and28 days was found.Conclusion and Relevance: Evidence on treatment options for subacute cough is weak. Better and larger trials, forexample exploring steroids, are needed.

Systematic review and simulation study of ignoring clustered data in surgical trials. Dell-Kuster S et al. Br. J Surg2018 Feb;105(3):182-191. Background: Multiple surgical procedures in a single patient are relatively common and lead to dependent (clustered)data. This dependency needs to be accounted for in study design and data analysis. Methods and Results: In a systematic review and simulation study the impact of ignoring clustered data in 50 herniatrials of patients with bilateral hernias was investigated. 40% of trials did not report on the analysis of clustered data,36% assessed outcomes by patient and not by hernia and 24% considered clustering in the design or analysis. In simulations, ignoring clustering led to an increased false positive (in 12%) or negative findings (in 15%), dependingon whether the patient or the hernia was the randomization unit.Conclusions and Relevance: Clustering was rarely considered in inguinal hernia trials. The simulations underline theimportance of considering clustering to avoid inappropriate study conclusions.

Cost estimates for HIV care and patient characteristics for health resource utilization from linkage of claimsdata with the Swiss HIV Cohort Study Leon-Reyes S. Clin Infect Dis 2018 Jul 18. doi: 10.1093/cid/ciy564. [Epub aheadof print]Background: Comprehensive and representative data on resource use is critical for health policy decision making butoften lacking.Methods and Results: We used privacy preserving probabilistic record linkage of claims from the largest health insurerand Swiss HIV Cohort Study data from 2012 and 2013 and modeled predictors for mean annual costs and risk groupsfor resource use. In the matched representative subsample of 1196 patients with claims data corrected mean totalcost (SE) in 2012 and 2013 were USD 30'462 (582) and USD 30'965 (629) and mainly accrued in ambulatory care forART (70% of mean costs). The low risk group for resource use had mean annual cost of USD 26'772 (536) and USD26'132 (589) in 2012 and 2013. In the moderate risk groups mean annual costs in 2012 and 2013 were higher by USD3'526 [1'907; 5'144] (13%) and 4'327 [2'662; 5'992] (17%) and in the high risk groups by USD 14'026 [8'763; 19'289 (52%)and 13'567[8'844; 18'288] (52%), respectively.Conclusions and relevance: In a representative subsample of patients from linkage of SHCS and claims data, ART wasthe major cost factor but patient profiling allowed identifying factors related to higher resource use.

MOST CITED PUBLICATION 2018 (FIRST AUTHOR)Briel M, Spoorenberg SMC, Snijders D, Torres A, Fernandez-Serrano S, Meduri GU, Gabarrus A, BlumCA, Confalonieri M, Kasenda B, Siemieniuk RAC, Boersma W, Bos WJW, Christ-Crain M. Corticoste-roids in Patients Hospitalized With Community-Acquired Pneumonia: Systematic Review and In-dividual Patient Data Metaanalysis. Clin Infect Dis 2018 Jan 18; 66(3): 346-54.

MOST CITED PUBLICATION 2018 ( OVERALL)Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M, Bouadma L, Luyt CE, Wolff M, ChastreJ, Tubach F, Kristoffersen KB, Burkhardt O, Welte T, Schroeder S, Nobre V, Wei L, Bucher HC, AnnaneD, Reinhart K, Falsey AR, Branche A, Damas P, Nijsten M, de Lange DW, Deliberato RO, Oliveira CF,Maravic-Stojkovic V, Verduri A, Beghe B, Cao B, Shehabi Y, Jensen JS, Corti C, van Oers JAH, Beis-huizen A, Girbes ARJ, de Jong E, Briel M, Mueller B. Effect of procalcitonin-guided antibiotic treat-ment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis2018 Jan; 18(1): 95-107.

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IMPACT OF RESEARCH FROM CEB

THE H-INDEXOur research is frequently cited as reflected in the h-index of senior researchers (Table 1).

Senior Researcher h-Index1) Standard value2) Mean citation frequencies per publication

Prof. Dr. M. Briel 44 2.6 34.86Prof. Dr. H.C. Bucher 65 2.5 37.17PD Dr. S Dell-Kuster 12 1.2 7.50PD Dr. L. Hemkens 13 1.3 26.80PD Dr. B. Kasenda 16 1.3 8.92PD Dr. M. Koller 37 2.2 14.85Prof. Dr. A. Nordmann 21 1.3 65.95

(per 03.01.2019)

Table 1. h-Index of CEB‘s senior researchers

1) The h-index starting from an author’s first publicaton allows to evaluate the performance of a single researcher and summarizes the publication and citation frequency in one figure. For example, a h-index of 10 means that a researcher has published 10 publications thathave been cited at least 10 times.

2) By dividing the h-index by the number of years since the first publication a standard value may be derived. A h-index of over 20 with research experience of 10 years and over 40 with research experience of 20 years are generally considered as excellent.

CITATION FREQUENCYThe citation frequency of publications of senior staff from CEB is a further measure of the relevanceof our research activity.

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(per 03.01.2019)

Figure 1. Citation frequency and number of indexed publications of senior researchers of CEB from 2001 to 2018 (Thompson Science Citation Index)

CEB RESEARCH

In 2018, researchers of CEB have published 61 publications in peer-reviewed journals.

Methodological researchCollaborators of the institute have published in 2018 13 methodological studies (1, 10, 13, 15 19,20, 22-24, 26, 31, 37, 58)1. Three publications deal with guidance for the reporting of research fromroutinely collected data (19, 20, 26), including the new reporting guideline for pharmacoepide-miological research (RECORD-PE). We also provided a general framework on the use of routinelycollected data for clinical trials (31). Two studies focus on approval evidence provided by the FDAto guide healthcare decisions (22, 24). One study concluded that missing data in trials are not adequately reported or dealt with in meta-analyses (15). One study deals with treatment effectsin observational studies using marginal structural models and randomized controlled trials investigating the same research question (10). Two publications deal with costs of randomizedcontrolled trials (2, 53). Further publications examine the consistency of abbreviated and extendedliteratures searches for retrieving relevant literature for clinical questions and on treatment effectsin randomised controlled trials of off-label use versus approved drug use (37, 23).

Evidence synthesisCollaborators of CEB were influential for the conduct of seven meta-analyses investigating the incidence and predictors of atrial fibrillation (3), bariatric surgery among patients with heart failure(7), dexmedetomidine in treatment and prevention of postoperative delir (11), the benefit of earlyinitiation of antiretroviral therapy (12), the efficacy and safety of ivermectin and albendazole forthe treatment of soil transmitted helmintic diseases (39), treatment of subacute cough in primarycare (52), and two individual patient data meta-analyses dealing with corticosteroids in the treatment of community acquired pneumonia and pro-calcitonin as a prognostic marker for mortality in patients with acute respiratory tract infections (51). We participate in the generationof two practice guidelines (25, 40).

Randomised controlled trialsCollaborators and associates of CEB have participated in the conduct of several trials (5, 56) andhave submitted two applications for the Investigator Initiated Clinical Trial call by the Swiss NationalScience Foundation. A large nationwide trial of routine prescription feedback and monitoring toreduce antibiotic use in primary care (NFP 72 Antimicrobial Resistance) is still ongoing. Anotherpilot trial where we investigate a new diagnostic device for acute bacterial rhinosinusitis startedrecruiting patients.

Non-randomized real world evidenceThree publications come from our international collaboration in observational data analyses inHIV covering important topics e.g. on the relevance of higher antiretroviral pill count and patientoutcome, or on the initiation of early therapy and risk of antiretroviral drug resistance (29, 53, 69).One publication was conducted within the Swiss HIV Cohort Study and evaluated predictors ofhigh resource in HIV care (27). Sabin Nsanzimana, a PhD student from Rwanda contributed fivepublications e.g. on the relevance of community workers to reduce attrition with antiretroviraltreatment programs (12, 30, 32, 35, 41). One publication investigated a new risk score for patientsin Switzerland with acute coronary syndromes who are referred to invasive coronary procedures,and one study investigated the risk of side infections in patients undergoing thoracic surgery whenoperating theater doors were opened during surgery (38, 47).

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1 Number refers to the list of publication (see section “Publications of CEB in 2018”).

CEB TEACHING

CEB teaches principles of evidence-based medicine, critical appraisal skills, basics in clinical epidemiology and clinical research methodology to medical students in the bachelor and mastersprogram at the University of Basel. Total undergraduate teaching obligations in 2018 were 151hours. In 2018, CEB was training eight PhD students and two master students. PhD and masterstudents have been involved in sixteen publications (2,12,13,16,19,20,22-24,30-32,35,41,53,58)and were first or senior authors in eight publications (10,22,23,24,31,35,36,58).

CEB CONSULTING

CEB is providing clinical epidemiology consultancy services within the Department Clinical Research at the University Hospital Basel. Thirteen publications originated from collaborative projects with the Department of Surgery (8, 9, 28, 33, 42-45, 48, 49, 59, 61). Among those, severalpublications resulted from neurosurgery.

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Team of BiostatisticiansElisabeth Deutschmann, Dr. Soheila Aghlmandi, Jim Young,

PD Dr. Salome Dell-Kuster(Dr. Guisi Moffa absent)

Clinical Epidemiology & Methodology TeamDr. Viktoria L. Gloy, Sirintip Sricharoenchai, Dr. Dominik Glinz

(Prof. Dr. Matthias Briel, Kimberly McCord, Dmitry Gryaznov, absent)

HEALTH TECHNOLOGY ASSESSMENT (HTA)

CEB has a consultancy mandate from the Swiss Federal Office of Public Health for a Health Technology Assessment report on the effectiveness of iron therapy in non-anemic patients withiron deficiency to be finished in 2019 and another consultancy mandate from the German “Institutfür Qualität und Wirtschaftlichkeit im Gesundheitswesen” (IQWIG).

SWISS TRANSPLANT COHORT STUDY

The Swiss Transplant Cohort Study (STCS) was founded in 2007 with major support of CEB and hascelebrated its 10 years anniversary. The staff of the data centre is associated with CEB. The studyinvolves all solid organ transplantation centers in Switzerland and includes 4574 solid organ trans-plant recipients by the end of 2018, Ten publications with cooperation of collaborators of the STCSdata center and researchers associated at CEB have resulted in 2018 (for details on these publica-tions see www.stcs.ch).

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Team of Swiss Transplant Cohort StudyPD Dr. Michael Koller, Madeleine Wick

CEB has established a large national and international scientific network and collaboration withclinical researchers. This has led to many publications; however, core funding to realize more ownresearch projects is still at the forefront of our goals in the coming years. Prof. Dr. Matthias Brielwas promoted by University of Basel to Titularprofessor and with Prof. Laurent Audigé, we havegained an additional assistant professor whose research focus is in outcomes research in orthopedicsurgery.

I feel privileged to work with an outstanding team of researchers and thank the entire team, DianaGrauwiler, my clinical research manager, and the foundation for their excellent work and financialsupport.

Prof. Heiner C. Bucher MD MPHDirector of the Institute

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Senior InvestigatorsPD Dr. Lars G. Hemkens, PD Dr. Salome Dell-Kuster, PD Dr. Michael Koller, Prof. Dr. Heiner C. Bucher(Prof. Dr. Matthias Briel absent)

Original Publications in Peer Reviewed Journals

(1) Ademi Z, Tomonaga Y, van Stiphout J, Glinz D, Gloy V, Raatz H, Bucher HC, SchwenkglenksM. Adaptation of cost-effectiveness analyses to a single country: the case of bariatric surgeryfor obesity and overweight. Swiss Med Wkly 2018 Jun 12; 148: w14626.

(2) Amstutz A, Schandelmaier S, Frei R, Surina J, Agarwal A, Alturki R, von Niederhausern B,von Elm E, Briel M, On Behalf Of The MARTA Group. Funding characteristics of randomisedclinical trials supported by the Swiss National Science Foundation: a retrospective cohortstudy. Swiss Med Wkly 2018 Jan 29; 148: w14587.

(3) Blum S, Meyre P, Aeschbacher S, Berger S, Auberson C, Briel M, Osswald S, Conen D. Incidenceand Predictors of Atrial Fibrillation Progression: A Systematic Review and Meta-Analysis. HeartRhythm 2018 Oct 23.

(4) Blum CA, Schuetz P, Nigro N, Winzeler B, Arici B, Refardt J, Urwyler SA, Rodondi N, Blum MR,Briel M, Mueller B, Christ-Crain M. Cosyntropin testing does not predict response to glucocorticoids in community-acquired pneumonia in a randomized controlled trial. Clin Endocrinol (Oxf) 2018 Nov 28.

(5) Bongard E, van der Velden AW, Cook J, Saville B, Beutels P, Munck Aabenhus R, Brugman C,Chlabicz S, Coenen S, Colliers A, Davies M, De Paor M, De Sutter A, Francis NA, Glinz D, Godycki-Cwirko M, Goossens H, Holmes J, Ieven M, de Jong M, Lindbaek M, Little P, Martinon-Torres F, Moragas A, Pauer J, Pfeiferova M, Radzeviciene-Jurgute R, Sundvall PD, Torres A, Touboul P, Varthalis D, Verheij T, Butler CC. Antivirals for influenza-Like Illness? A randomisedControlled trial of Clinical and Cost effectiveness in primary CarE (ALIC(4) E): the ALIC(4) E protocol. BMJ Open 2018 Jul 12; 8(7): e021032.

(6) Briel M, Spoorenberg SMC, Snijders D, Torres A, Fernandez-Serrano S, Meduri GU, GabarrusA, Blum CA, Confalonieri M, Kasenda B, Siemieniuk RAC, Boersma W, Bos WJW, Christ-Crain M.Corticosteroids in Patients Hospitalized With Community-Acquired Pneumonia: SystematicReview and Individual Patient Data Metaanalysis. Clin Infect Dis 2018 Jan 18; 66(3): 346-54.

(7) Berger S, Meyre P, Blum S, Aeschbacher S, Ruegg M, Briel M, Conen D. Bariatric surgery amongpatients with heart failure: a systematic review and meta-analysis. Open Heart 2018 5(2):e000910.

(8) Brosi P, Glauser PM, Speich B, Kaser SA, Maurer CA. Prophylactic Intraperitoneal Onlay MeshReinforcement Reduces the Risk of Incisional Hernia, Two-Year Results of a Randomized Clinical Trial. World J Surg 2018 Nov 20.

(9) Dell-Kuster S, Droeser RA, Schäfer J, Gloy V, Ewald H, Schandelmaier S, Hemkens LG, Bucher HC, Young J, Rosenthal R. Systematic review and simulation study of ignoring clustered data in surgical trials. British Journal of Surgery 2018 Feb; 105(3): 182-91.

(10) Ewald H, Speich B, Ladanie A, Bucher HC, Ioannidis JP, Hemkens LG. Marginal structuralmodels and other analyses allow multiple estimates of treatment effects in randomized clinical trials: meta-epidemiological analysis. J Clin Epidemiol 2018 Nov 10.

PUBLICATIONS OF CEB IN 2018

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(11) Flukiger J, Hollinger A, Speich B, Meier V, Tontsch J, Zehnder T, Siegemund M. Dexmedetomi-dine in prevention and treatment of postoperative and intensive care unit delirium: a systematic review and meta-analysis. Ann Intensive Care 2018 Sep 20; 8(1): 92.

(12) Ford N, Migone C, Calmy A, Kerschberger B, Kanters S, Nsanzimana S, Mills EJ, Meintjes G, Vitoria M, Doherty M, Shubber Z. Benefits and risks of rapid initiation of antiretroviral therapy.AIDS 2018 Jan 2; 32(1): 17-23.

(13) Hemkens LG, Ewald H, Naudet F, Ladanie A, Shaw JG, Sajeev G, Ioannidis JPA. Interpretationof epidemiologic studies very often lacked adequate consideration of confounding. J ClinEpidemiol 2018 Jan; 93: 94-102.

(14) Illerhaus G, Schorb E, Kasenda B. Novel agents for primary central nervous system lymphoma:evidence and perspectives. Blood 2018 Aug 16; 132(7): 681-8.

(15) Kahale LA, Diab B, Brignardello-Petersen R, Agarwal A, Mustafa RA, Kwong J, Neumann I, Li L,Lopes LC, Briel M, Busse JW, Iorio A, Vandvik PO, Alexander PE, Guyatt G, Akl EA. Systematicreviews do not adequately report or address missing outcome data in their analyses: a methodological survey. Journal of Clinical Epidemiology 2018 Jul 1; 99: 14-23.

(16) Keller F, Dhaini S, Briel M, Henrichs S, Hochsmann C, Kalbermatten D, Kunzli N, Mollet A, Puelacher C, Schmidt-Trucksass A, von Niederhausern B, De Geest S. How to Conceptualizeand Implement a PhD Program in Health Sciences-The Basel Approach. J Med Educ CurricDev 2018 Jan-Dec; 5.

(17) Kuipers J, Moffa G, Kuipers E, Freeman D, Bebbington P. Links between psychotic and neuroticsymptoms in the general population: an analysis of longitudinal British National Survey datausing Directed Acyclic Graphs. Psychol Med 2018 May 29: 1-8.

(18) Kuipers J, Thurnherr T, Moffa G, Suter P, Behr J, Goosen R, Christofori G, Beerenwinkel N. Mutational interactions define novel cancer subgroups. Nat Commun 2018 Oct 19; 9(1): 4353.

(19) Kwakkenbos L, Imran M, McCord KA, Sampson M, Frobert O, Gale C, Hemkens LG, LanganSM, Moher D, Relton C, Zwarenstein M, Benchimol EI, Boutron I, Campbell MK, Erlinge D, JawadS, Ravaud P, Rice DB, Sauve M, van Staa TP, Thabane L, Uher R, Verkooijen HM, Juszczak E,Thombs BD. Protocol for a scoping review to support development of a CONSORT extensionfor randomised controlled trials using cohorts and routinely collected health data. BMJ Open2018 Aug 5; 8(8): e025266.

(20) Kwakkenbos L, Juszczak E, Hemkens LG, Sampson M, Frobert O, Relton C, Gale C, ZwarensteinM, Langan SM, Moher D, Boutron I, Ravaud P, Campbell MK, McCord KA, van Staa TP, ThabaneL, Uher R, Verkooijen HM, Benchimol EI, Erlinge D, Sauve M, Torgerson D, Thombs BD. Protocolfor the development of a CONSORT extension for RCTs using cohorts and routinely collectedhealth data. Res Integr Peer Rev 2018 Mar: 9.

(21) Labhardt ND, Ringera I, Lejone TI, Klimkait T, Muhairwe J, Amstutz A, Glass TR. Effect of Offering Same-Day ART vs Usual Health Facility Referral During Home-Based HIV Testing onLinkage to Care and Viral Suppression Among Adults With HIV in Lesotho: The CASCADE Randomized Clinical Trial. JAMA 2018 Mar 20; 319(11): 1103-12.

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(22) Ladanie A, Ewald H, Kasenda B, Hemkens LG. How to use FDA drug approval documentsfor evidence syntheses. BMJ 2018 362.

(23) Ladanie A, Ioannidis JPA, Stafford RS, Ewald H, Bucher HC, Hemkens LG. Off-label treatmentswere not consistently better or worse than approved drug treatments in randomized trials. J Clin Epidemiol 2018 Feb; 94: 35-45.

(24) Ladanie A, Speich B, Naudet F, Agarwal A, Pereira TV, Sclafani F, Martin-Liberal J, Schmid T,Ewald H, Ioannidis JPA, Bucher HC, Kasenda B, Hemkens LG. The Comparative Effectivenessof Innovative Treatments for Cancer (CEIT-Cancer) project: Rationale and design of the data-base and the collection of evidence available at approval of novel drugs. Trials 2018 Sep 19;19(1): 505.

(25) Lamontagne F, Rochwerg B, Lytvyn L, Guyatt GH, Moller MH, Annane D, Kho ME, Adhikari NKJ,Machado F, Vandvik PO, Dodek P, Leboeuf R, Briel M, Hashmi M, Camsooksai J, Shankar-HariM, Baraki MK, Fugate K, Chua S, Marti C, Cohen D, Botton E, Agoritsas T, Siemieniuk RAC. Corticosteroid therapy for sepsis: a clinical practice guideline. BMJ 2018; 362: k3284.

(26) Langan SM, Schmidt SA, Wing K, Ehrenstein V, Nicholls SG, Filion KB, Klungel O, Petersen I, Sorensen HT, Dixon WG, Guttmann A, Harron K, Hemkens LG, Moher D, Schneeweiss S,Smeeth L, Sturkenboom M, von Elm E, Wang SV, Benchimol EI. The reporting of studies conducted using observational routinely collected health data statement for pharmacoepi-demiology (RECORD-PE). BMJ 2018; 363: k3532.

(27) Leon-Reyes S, Schafer J, Fruh M, Schwenkglenks M, Reich O, Schmidlin K, Staehelin C, Battegay M, Cavassini M, Hasse B, Bernasconi E, Calmy A, Hoffmann M, Schoeni-Affolter F,Zhao H, Bucher HC. Cost estimates for HIV care and patient characteristics for health resourceutilisation from linkage of claims data with the Swiss HIV Cohort Study. Clin Infect Dis 2018Jul 18.

(28) Leu S, Boulay JL, Thommen S, Bucher HC, Stippich C, Mariani L, Bink A. Preoperative Two-Dimensional Size of Glioblastoma is Associated with Patient Survival. World Neurosurg 2018Apr 18.

(29) Lodi S, Gunthard HF, Dunn D, Garcia F, Logan R, Jose S, Bucher HC, Scherrer AU, SchneiderMP, Egger M, Glass TR, Reiss P, van Sighem A, Boender TS, Phillips AN, Porter K, Hawkins D, Moreno S, Monge S, Paraskevis D, Simeon M, Vourli G, Sabin C, Hernan MA. Effect of immediateinitiation of antiretroviral treatment on the risk of acquired HIV drug resistance. AIDS 2018Jan 28; 32(3): 327-35.

(30) Mbituyumuremyi A, Van Nuil JI, Umuhire J, Mugabo J, Mwumvaneza M, Makuza JD, UmutesiJ, Nsanzimana S, Gupta N. Controlling hepatitis C in Rwanda: a framework for a national response. Bull World Health Organ 2018 Jan 1; 96(1): 51-8.

(31) McCord KA, Al-Shahi Salman R, Treweek S, Gardner H, Strech D, Whiteley W, Ioannidis JPA, Hemkens LG. Routinely collected data for randomized trials: promises, barriers, and implications. Trials 2018 Jan 11; 19(1): 29.

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(32) Mutagoma M, Sebuhoro D, Nyemazi JP, Mills EJ, Forrest JI, Remera E, Murindabigwi A, Semakula M, Nsanzimana S. The role of community health workers and local leaders in reducing attrition among participant in the AIDS indicator survey and HIV incidence in a national cohort study in Rwanda. BMC Public Health 2018 Mar 9; 18(1): 338.

(33) Nebiker CA, Staubli S, Schafer J, Bingisser R, Christ-Crain M, Dell-Kuster S, Mueller C, ScamardiK, Viehl CT, Kolleth D, von Holzen U, Oertli D, Rosenthal R. Cortisol Outperforms Novel Cardio-vascular, Inflammatory, and Neurohumoral Biomarkers in the Prediction of Outcome in AcutePancreatitis. Pancreas 2018 Jan; 47(1): 55-64.

(34) Nordmann A, Fernandes M, Olde Rikkert MGM. Look before you SPRINT: look at the data andlook at the consequences. Swiss Med Wkly 2018 Jul 1, 148: w14629.

(35) Nsanzimana S, Forrest JI. Many pathways to ending AIDS by 2030. Lancet HIV 2018 Aug; 5(8):e407-e8.

(36) Nsanzimana S, McArdle F, Remera E, Mulindabigwi A, Ribakare M, Ndimubanzi P, KayirangwaE, Baribwira C, Riedel DJ, Ntaganira J. Viral Suppression in a Nationwide Sample of HIV-infectedChildren on Antiretroviral Therapy in Rwanda. Pediatr Infect Dis J 2018 May 21.

(37) Nussbaumer-Streit B, Klerings I, Wagner G, Heise TL, Dobrescu AI, Armijo-Olivo S, Stratil JM,Persad E, Lhachimi SK, Van Noord MG, Mittermayr T, Zeeb H, Hemkens LG, Gartlehner G. Abbreviated literature searches were viable alternatives to comprehensive searches: A meta-epidemiological study. J Clin Epidemiol 2018 Jun 1.

(38) Obeid S, Frangieh AH, Raber L, Yousif N, Gilhofer T, Yamaji K, Jaguszewski M, Aghlmandi S,Adams J, Bockhorn Y, Templin C, Stahli BE, Juni P, Rodondi N, Mach F, Roffi M, Windecker S,Maier W, Nietlispach F, Matter CM, Klingenberg R, Luscher TF. Prognostic Value of SYNTAXScore II in patients with acute coronary syndromes referred for invasive management: A subanalysis from the SPUM and COMFORTABLE AMI Cohorts. Cardiol Res Pract 2018 Sep 25:9762176.

(39) Palmeirim MS, Hurlimann E, Knopp S, Speich B, Belizario V, Jr., Joseph SA, Vaillant M, OlliaroP, Keiser J. Efficacy and safety of co-administered ivermectin plus albendazole for treatingsoil-transmitted helminths: A systematic review, meta-analysis and individual patient dataanalysis. PLoS Negl Trop Dis 2018 Apr; 12(4): e0006458.

(40) Emons G, Steiner E, Vordermark D, Uleer C, Bock N, Paradies K, Ortmann O, Aretz S, MallmannP, Kurzeder C, Hagen V, van Oorschot B, Hocht S, Feyer P, Egerer G, Friedrich M, Cremer W, ProttFJ, Horn LC, Prompeler H, Langrehr J, Leinung S, Beckmann MW, Kimmig R, Letsch A, ReinhardtM, Alt-Epping B, Kiesel L, Menke J, Gebhardt M, Steinke-Lange V, Rahner N, Lichtenegger W,Zeimet A, Hanf V, Weis J, Mueller M, Henscher U, Schmutzler RK, Meindl A, Hilpert F, Panke JE,Strnad V, Niehues C, Dauelsberg T, Niehoff P, Mayr D, Grab D, Kreissl M, Witteler R, Schorsch A,Mustea A, Petru E, Hubner J, Rose AD, Wight E, Tholen R, Bauerschmitz GJ, Fleisch M, Juhasz-Boess I, Lax S, Runnebaum I, Tempfer C, Nothacker MJ, Blodt S, Follmann M, Langer T, Raatz H, Wesselmann S, Erdogan S. Interdisciplinary Diagnosis, Therapy and Follow-up of Patients with Endometrial Cancer. Guideline (S3-Level, AWMF Registry Number 032/034-OL,April 2018) - Part 2 with Recommendations on the Therapy and Follow-up of EndometrialCancer, Palliative Care, Psycho-oncological/Psychosocial Care/Rehabilitation/Patient Information and Healthcare Facilities. Geburtshilfe Frauenheilkd 2018 Nov; 78(11): 1089-109.

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(41) Riedel DJ, Stafford KA, Memiah P, Coker M, Baribwira C, Sebeza J, Karorero E, Nsanzimana S,Morales F, Redfield RR. Patient-level outcomes and virologic suppression rates in HIV-infectedpatients receiving antiretroviral therapy in Rwanda. Int J STD AIDS 2018 Aug; 29(9): 861-72.

(42) Roethlisberger M, Achermann R, Bawarjan S, Stienen MN, Fung C, D’Alonzo D, Maldaner N,Ferrari A, Corniola MV, Schöni D, Goldberg J, Valsecchi D, Robert T, Maduri R, Seule MA, Burk-hardt J-K, Marbacher S, Bijlenga P, Blackham KA, Bucher HC, Mariani L, Guzman R, ZumofenDW, Swiss SOSg. Impact of aneurysm multiplicity on treatment and outcome after aneurysmalsubarachnoid hemorrhage. Neurosurgery 2018 Aug 3: nyy331-nyy.

(43) Roethlisberger M, Achermann R, Bawarjan S, Stienen MN, Fung C, D'Alonzo D, Maldaner N,Ferrari A, Corniola MV, Schoni D, Valsecchi D, Maduri R, Seule MA, Burkhardt JK, Marbacher S,Bijlenga P, Blackham KA, Bucher HC, Mariani L, Guzman R, Zumofen DW, Swiss SOSSG. Predictors of occurrence and anatomic distribution of multiple aneurysms in patients withaneurysmal subarachnoid hemorrhage. World Neurosurg 2018 Mar; 111: e199-e205.

(44) Roethlisberger M, Moffa G, Fisch U, Wiggli B, Schoen S, Kelly C, Leu S, Croci D, Zumofen DW,Cueni N, Nogarth D, Schulz M, Bucher HC, Weisser-Rohacek M, Wasner MG, Widmer AF, Mariani L. Effectiveness of a chlorhexidine dressing on silver-coated external ventricular drainassociated colonization/infection - a prospective single-blinded randomized controlled clinical trial (EVDAI-Study). Clin Infect Dis 2018 May 4.

(45) Roethlisberger M, Moffa G, Fisch U, Wiggli B, Schoen S, Kelly C, Leu S, Croci D, Zumofen DW,Cueni N, Nogarth D, Schulz M, Bucher HC, Weisser-Rohacek M, Wasner M-G, Widmer AF, Mariani L. Effectiveness of a chlorhexidine dressing on silver-coated external ventricular drain–associated colonization and infection: A prospective single-blinded randomized controlledclinical trial. Clinical Infectious Diseases 2018 Nov 28: ciy393-ciy.

(46) Roth JA, Battegay M, Juchler F, Vogt JE, Widmer AF. Introduction to machine learning in digitalhealthcare epidemiology. Infect Control Hosp Epidemiol 2018 Nov 5: 1-6.

(47) Roth JA, Juchler F, Dangel M, Eckstein FS, Battegay M, Widmer AF. Frequent Door openingsduring cardiac surgery are associated with increased risk for surgical site infection: A prospective observational study. Clin Infect Dis 2018 Oct 13.

(48) Saxer F, Studer P, Jakob M, Suhm N, Rosenthal R, Dell-Kuster S, Vach W, Bless N. Minimally in-vasive anterior muscle-sparing versus a transgluteal approach for hemiarthroplasty in femoralneck fractures-a prospective randomised controlled trial including 190 elderly patients. BMC Geriatr 2018 Sep 21; 18(1): 222.

(49) Schaefer T, Ramadoss A, Leu S, Tintignac L, Tostado C, Bink A, Schurch C, Muller J, Scharer J,Moffa G, Demougin P, Moes S, Stippich C, Falbo S, Neddersen H, Bucher HC, Frank S, Jeno P,Lengerke C, Ritz MF, Mariani L, Boulay JL. Regulation of glioma cell invasion by 3q26 geneproducts PIK3CA, SOX2 and OPA1. Brain Pathol 2018 Nov 7.

(50) Schuetz P, Bolliger R, Merker M, Christ-Crain M, Stolz D, Tamm M, Luyt CE, Wolff M, SchroederS, Nobre V, Reinhart K, Branche A, Damas P, Nijsten M, Deliberato RO, Verduri A, Beghe B, CaoB, Shehabi Y, Jensen JS, Beishuizen A, de Jong E, Briel M, Welte T, Mueller B. Procalcitonin-guided antibiotic therapy algorithms for different types of acute respiratory infections basedon previous trials. Expert Rev Anti Infect Ther 2018 Jul; 16(7): 555-64.

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(51) Schuetz P, Wirz Y, Sager R, Christ-Crain M, Stolz D, Tamm M, Bouadma L, Luyt CE, Wolff M, Chastre J, Tubach F, Kristoffersen KB, Burkhardt O, Welte T, Schroeder S, Nobre V, Wei L, BucherHC, Annane D, Reinhart K, Falsey AR, Branche A, Damas P, Nijsten M, de Lange DW, DeliberatoRO, Oliveira CF, Maravic-Stojkovic V, Verduri A, Beghe B, Cao B, Shehabi Y, Jensen JS, Corti C,van Oers JAH, Beishuizen A, Girbes ARJ, de Jong E, Briel M, Mueller B. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis 2018 Jan; 18(1): 95-107.

(52) Speich B, Thomer A, Aghlmandi S, Ewald H, Zeller A, Hemkens LG. Treatments for subacutecough in primary care: systematic review and meta-analyses of randomised clinical trials. Br J Gen Pract 2018 Sep 10.

(53) Speich B, von Niederhäusern B, Blum CA, Keiser J, Schur N, Fürst T, Kasenda B, Christ-CrainM, Hemkens LG, Pauli-Magnus C, Schwenkglenks M, Briel M. Retrospective assessment of resource use and costs in two investigator-initiated randomized trials exemplified a comprehensive cost item list. Journal of Clinical Epidemiology 2018 Apr; 96: 73-83.

(54) Speich B, von Niederhausern B, Schur N, Hemkens LG, Furst T, Bhatnagar N, Alturki R, Agarwal A, Kasenda B, Pauli-Magnus C, Schwenkglenks M, Briel M. Systematic review on costs and resource use of randomized clinical trials shows a lack of transparent and comprehensive data. J Clin Epidemiol 2018 Apr; 96: 1-11.

(55) Stirrup OT, Copas AJ, Phillips AN, Gill MJ, Geskus RB, Touloumi G, Young J, Bucher HC, BabikerAG. Predictors of CD4 cell recovery following initiation of antiretroviral therapy among HIV-1positive patients with well-estimated dates of seroconversion. HIV Med 2018 Mar; 19(3): 184-94.

(56) Urech C, Grossert A, Alder J, Scherer S, Handschin B, Kasenda B, Borislavova B, Degen S, ErbJ, Faessler A, Gattlen L, Schibli S, Werndli C, Gaab J, Berger T, Zumbrunn T, Hess V. Web-basedstress management for newly diagnosed patients with cancer (STREAM): A randomized, wait-list controlled intervention study. J Clin Oncol 2018 Mar 10; 36(8): 780-8.

(57) Vach W, Saxer F, Holsgaard-Larsen A, Overgaard S, Farin-Glattacker E, Bless N, Bucher HC,Jakob M. Rationale and methods of an observational study to support the design of a nationwide surgical registry: the MIDAS study. Swiss Med Wkly 2018 Nov 5; 148: w14680.

(58) von Niederhausern B, Guyatt GH, Briel M, Pauli-Magnus C. Academic response to improvingvalue and reducing waste: A comprehensive framework for INcreasing QUality In patient-oriented academic clinical REsearch (INQUIRE). PLoS Med 2018 Jun; 15(6): e1002580.

(59) von Strauss Und Torney M, Aghlmandi S, Zeindler J, Nowakowski D, Nebiker CA, KettelhackC, Rosenthal R, Droeser RA, Soysal SD, Hoffmann H, Mechera R. High-resolution standardization reduces delay due to workflow disruptions in laparoscopic cholecystectomy.Surg Endosc 2018 May 21.

(60) Young J, Smith C, Teira R, Reiss P, Jarrin Vera I, Crane H, Miro JM, D'Arminio Monforte A, SaagM, Zangerle R, Bucher HC, Antiretroviral Therapy Cohort C. Antiretroviral pill count and clinicaloutcomes in treatment-naive patients with HIV infection. HIV Med 2018 Feb; 19(2): 132-42.

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(61) Zumofen DW, Roethlisberger M, Achermann R, Bawarjan S, Stienen MN, Fung C, D'Alonzo D,Maldaner N, Ferrari A, Corniola MV, Schoeni D, Goldberg J, Valsecchi D, Robert T, Maduri R,Seule M, Burkhardt JK, Marbacher S, Bijlenga P, Blackham KA, Bucher HC, Mariani L, GuzmanR. Factors associated with clinical and radiological status on admission in patients with aneurysmal subarachnoid hemorrhage. Neurosurg Rev 2018 Feb 10.

Editorials, Research Letters, Letters and Non-Peer Reviewed Publications

(1) Hemkens LG. Besser entscheiden mit Big Data. IMPLICONplus 2018 2018;08.

(2) Hemkens LG. How routinely collected data for randomized trials provide long-term randomized real world evidence [Invited Commentary]. JAMA Network Open 2018.

(3) Hemkens LG. New Trials thematic series on big data for randomized trials. BMC On Medicine2018 [blog: 18 May 2018].

(4) Hemkens LG, McCord KA. Big data for clinical trials: a perfect blend. BMC On Medicine 2018[blog: 11 Jan 2018].

(5) Ladanie A, Ioannidis JPA, Stafford RS, Ewald H, Bucher HC, Hemkens LG, Hemkens LG. Theauthors respond. J Clin Epidemiol 2018 May 22.

(6) Ladanie A, Ioannidis JPA, Stafford RS, Ewald H, Bucher HC, Hemkens LG, Hemkens LG. Off-label prescription: experience is a gloomy lantern that does not even illuminate its bearer.Author response. J Clin Epidemiol 2018 Sep; 101: 127-8.

(7) Briel M, Spoorenberg SMC, Bos WJW, Christ-Crain M. Author reply Clin Infect Dis2018;67(9):1467-1468

Book Chapters

(1) Bucher HC. 3.3 Indirekte Vergleiche neuer Therapieverfahren und Marktzugangsbewertung- eine kritische Zwischenbilanz. AMNOG-Report 2018; Nutzenbewertung von Arzneimittelnin Deutschland Schwerpunkt: Arztinformationssystem - Wie kommen die Ergenbisse in diePraxis? Beiträge zur Gesundheitsökonomie und Versorgungsforschung (Band 22). Hamburg,Germany: Andreas Storm, DAK-Gesundheit; 2018 Jun.

(2) Johnston BC, Patrick DL, Devji T, Maxwell LJ, Bingham III CO, Beaton D, Boers M, Briel M, BusseJW, Carrasco-Labra A, Christensen R, da Costa BR, Ecceleston C, El Dib R, Lyddiatt A, OsteloRW, Shea B, Singh J, Terwee CB, Williamson P, Gagnier J, Tugwell P, Guyatt GH. Chapter 18: Patient-reported outcomes. In: Higgins JPT, Thomas J, Chandler J, Cumpston MS, Li T, PageMJ, Welch V. Cochrane Handbook for Systematic Reviews of Interventions. London: Cochrane 2018.

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Presentations

(1) Briel M. von Niederhäusern B, Guyatt G, Pauli-Magnus C. Academic response to improvingvalue and reducing waste: Delphi consensus on a comprehensive framework to INcrease QUality In academic clinical REsearch (INQUIRE). SGAIM, Basel, Switzerland. 2018 May 30-Jun 1

(2) Briel M. Evidence-based trial methods to improve trial efficiency. Health Services ResearchUnit University of Aberdeen, Aberdeen, United Kingdom. 2018 Nov 21 (invited talk)

(3) Briel M. Evidence-based clinical research. Keynote Lecture at the UKBB Research Day, Basel,Switzerland. 2018 Oct 23 (invited talk)

(4) Briel M. The Adherence to SPIrit REcommendations (ASPIRE) Study. Swiss Federal Office ofPublic Health, Bern-Liebefeld, Switzerland. 2018 Oct 2 (invited talk)

(5) Deschodt M, Jenkins R, Blozik E, Briel M, Probst-Hensch N, Quinto C, Schwenkglenks M, ZellerA, Zuniga F, De Geest S. Implementation of a nurse-led community-based care model for senior citizens in Canton Basel-Landschaft: the INSPIRE project. Zentralschweizer Pflege -symposium Management & ANP, Lucerne, Switzerland. 2018 Oct 16-17 (oral presentation)

(6) Briel M. Quality Framework for Clinical Trials. Swiss TPH Summer Symposium, Clinical Research in Resource Limited Settings, Basel, Switzerland. 2018 June 28 (invited talk)

(7) Briel M. How to handle problems in the conduct of investigator-initiated clinical trials? Meeting of the European Commission for Research in the Health Sciences, Brussels, Belgium.2018 May 30 (invited talk)

(8) Briel M. Increasing Quality In clinical Research (INQUIRE) – An academic response to the value& waste discussion. Swiss Federal Office of Public Health, Bern, Switzerland. 2018 Feb 20 (invited talk)

(9) Bucher HC. Möglichkeiten und Grenzer der Evidence-based Medicine. 12 InterdisziplinäresVersicherungsmedizinisches Kolloquium, Lucerne, Switzerland. 2018 Dec 6. (invited talk)

(10) Bucher HC. Registry based pragmatic randomized controlled trials for nationwide evaluationsof health care interventions. i~HD Annual Conference 2018, Gothenburg, Sweden. 2018 November 19-20. (invited talk)

(11) Ewald H, Ioannidis JP, Ladanie A, Mc Cord K, Bucher HC, Hemkens LG. Haben nichtrando-misierte Studien mit kausalen Modellen und randomisierte Studien gleiche Ergebnisse? Einemeta-epidemiologische Studie. 19 Annual meeting of the German Network for Evidence-based Medicine, Graz, Austria. 2018 Mar 9.

(12) Ewald H, Speich B, Ladanie A, Bucher HC, Ioannidis JP, Hemkens LG. Causal modelling inRCTs: how results compare to intention-to-treat and other analytical methods. A meta-epidemiological analysis. . Cochrane Colloquium, Edinburgh, Scotland. 2018 Sep 17.

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(13) Gryaznov D. Smartphone app and carbon monoxide self-monitoring support for smokingcessation: a randomised controlled trial nested into the Swiss HIV Cohort Study. Joint AnnualConference of the Swiss Society of Pneumology 2018, St.Gallen, Switzerland. 2018 May 25.

(14) Hemkens LG. Glaube und Wissen. Unsicherheit und Präzision. Big Data und Medizin. University of Basel, Basel, Switzerland. 2018 May 4. (invited talk)

(15) Hemkens LG. Randomized Real World Evidence. 4 European Society of Pharmacogenomicsand Personalised Therapy (ESPT) Summer School, Geneva, Switzerland. Sep 26. (invited tald)

(16) Hemkens LG. Routinedaten, Register und randomisierte Studien - die perfekte Mischung. 5 Board der Charite Initiative für MS Patienten, Berlin, Germany. 2018 Oct 17. (invitedLecture)

(17) Hemkens LG. Use of Insurance data for clinical research or clinical trials. Bern Institute of Primary Health Care (BIHAM) Meeting, Bern, Switzerland. 2018 Jul 17. (invited talk)

(18) Moffa G. Causal inference with directed acyclic graphs: A case study in psychosis. CMStatistics2018, Pisa, Italy. 2018. (invited talk)

(19) Moffa G. Causal inference with directed acyclic graphs: outlook for future BES? Basel Epidemiology Seminar, Basel, Switzerland. 2018 Aug 17.

(20) Moffa G. Oncology precision medicine: challenges and opportunities in trial design. Technologies And Translational Research Conference, Zurich, Switzerland. 2018 Jun 18. (invited talk)

(21) Nussbaumer J, Dell-Kuster S, Heim S, Heinzelmann V. Validierungsstudie von CLASSIC -Classification of Intraoperative Complications- Anwendung in der operativen Gynäkologie.62 Kongress Deutsche Gesellschaft für Gynäkologie und Geburtshilfe eV, Berlin, Germany.2018 Oct 31 – Nov 3.

(22) Schandelmaier S, Briel M, Sun X, Dahabreh I, Walsh M, Thabane L, Hoes A, Weiss N, GagnierJ, Sauerbrei W, Hayward R, Ioannidis J, Van der Heijden G, Borenstein M, Schmidt C, VaradhanR, Guyatt G. Development of new instrument to assess the credibility of effect modifiers. 26th Cochrane Colloquium, Edinburgh, United Kingdom. 2018 Sept 15-18.

(23) Schandelmaier S, Briel M, Sun X, Dahabreh I, Walsh M, Thabane L, Hoes AW, Gagnier JJ, Sau-erbrei W, Hayward RA, Ioannidis JP, Van der Heijden GJ, Borenstein M, Schmid CH, VaradhanR, Guyatt GH. A new instrument to assess the credibility of effect modification. Guidelines International Network (G-I-N) Conference, Manchester, United Kingdom. 2018 Sept 11-14.

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Posters and Abstracts

(1) Berger S, Meyre P, Blum S, Ruegg M, Briel M, Conen D. Heart failure and bariatric surgery: A systematic review and meta-analysis. European Society of Cardiology Congress, Munich, Germany. 2018Aug 25-29

(2) Blum S, Meyre P, Aeschbacher S, Berger S, Auberson C, Briel M, Schnabel RB, Osswald S, ConenD. Incidence and Clinical Predictors of Atrial Fibrillation Progression: A Systematic Review andMeta-Analysis. Swiss Society of Cardiology Annual Meeting, Basel, Switzerland. 2018 June 6-8.

(3) Blum S, Meyre P, Aeschbacher S, Berger S, Auberson C, Briel M, Schnabel RB, Osswald S, ConenD. Incidence and Clinical Predictors of Atrial Fibrillation Progression: A Systematic Review andMeta-Analysis. European Society of Cardiology Congress, Munich,Germany. 2018 Aug 25-29.

(4) Briel M, Wilde M, Kuenzli N, Finke D, Pauli-Magnus C, Schwaller J. “SciMo“: a program to train medical students’ competences to compete at scientific conferences. . International Association for Medical Education (AMEE) Conference, Basel, Switzerland. 2018 Aug 25-29.

(5) Deschodt M, Blozik E, Briel M, Probst-Hensch N, Quinto C, Schwenkglenks M, Zeller A, De GeestS. Implementation of a nurse-led community-based care program for senior citizens in Baselland(CH): the INSPIRE project. 70th Annual Scientific Meeting of the Gerontological Society of America, Boston, United States of America. 2018 Nov 14-18.

(6) Ewald H, Ladanie A, Klerings I, Wagner G, Heise TL, Dobrescu AI, Armijo-Olivo S, Stratil JM, Lhachimi SK, Van Noord M, Mittermayr T, Gartlehner G, Nussbaumer-Streit B, Hemkens LG. Wieverändern sich die Hauptergebnisse von Systematic Reviews durch weniger aufwendige Literatursuchen? Eine meta-epidemiologische Analyse. 19 Annual meeting of the German Network for Evidence-based Medicine, Graz, Austria. 2018 Mar 9.

(7) Kasenda B, von Elm E, Briel M. Prediction of recruitment in randomized clinical trials. SGAIM,Basel, Switzerland. 2018 May 30-Jun 1.

(8) Leu S, Ramadoss A, Schaefer T, Tintignac L, Tostado C, Bink A, Moffa G, Demougin P, Moes S,Mariani L, Boulay J. Regulation of glioma cell invasion by 3q26 gene products PIK3CA, SOX2and OPA1. Neuro-Oncology, 13th Meeting of the European Association of Neurooncology,Stockholm, Sweden 2018 Oct 10.

(9) Von Strauss M, Moffa G, Kettelhack C, Bucher HC, Kaech M, Haak F, Paterson HM. Interval resection in complicated diverticulitis: A comparative population based analysis of two healthcare systems. ESCP Nice 2018, thirteenth scientific and annual meeting of the European Society of Coloproctology, Nice, France. 2018 Sep 26.

(10) Meyre P, Blum S, Berger S, Aeschbacher S, Schöpfer H, Briel M, Niessner A, Osswald S, Conen D.Incidence and risk factors for all-cause hospitalizations in patients with atrial fibrillation: A systematic review and meta-analysis. European Society of Cardiology Congress, Munich, Germany. 2018 Aug 25-29. (poster presentation)

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(11) Meyre P, Blum S, Berger S, Aeschbacher S, Schöpfer H, Briel M, Niessner A, Osswald S, Conen D.Incidence and risk factors for all-cause hospitalizations in patients with atrial fibrillation: A systematic review and meta-analysis. Swiss Society of Cardiology Annual Meeting, Basel, Switzerland. 2018 June 6-8. (poster presentation)

(12) Nsanzimana S, Ribakare M, Remera E, Suthar AB, Riedel DJ, Mills E, Bucher HC. Treating multiclass-resistant HIV+ patients in Rwanda using a public health approach. Conference onRetroviruses and Opportunistic Infections (CROI) 2018, Boston, United States of America. 2018March 4–7.

(13) Leu S, Ramadoss A, Schaefer T, Tintignac L, Tostado C, Bink A, Frank S, Moffa G, Demougin P,Moes S, Stippich C, Falbo S, Neddersen H, Bucher HC, Lengerke C, Jenö P, Ritz M-F, Mariani L,Boulay J-L. Regulation of glioma cell invasion by 3q26 gene products PIK3CA, SOX2 and OPA1.Joint Annual meeting 2018 of Swiss Society of Neurosurgery and Swiss Society of Neuroradiology, Lugano, Switzerland. 2018 May 24.

(14) Speich B, von Niederhausern B, Schur N, Gryaznov D, Schwenkglenks M, Briel M. Transparentassessment of research use and costs of randomised clinical trials: a case series. 25th CochraneColloquium Edinburgh, Scotland. 2018 Sep 15.

(15) Young J, Nitulescu R, Cooper C, Cox J, Martel-Laferriere V, Hull M, Saeed S, Klein MB. HepatitisC treatment uptake in the era of direct-acting antivirals. 22th International Workshop on HIVObservational Databases, Fuengirola, Spain. 2018 Mar 22-24.

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HIV INFECTION, SWISS HIV COHORT STUDY AND MULTICOHORT PROJECTS

HIV and non-HIV related morbidity and its associated resource use and costs in the SwissHIV Cohort Study (SHCS): A data linkage pilot study*There exists little data on costs and resource use for in hospital and ambulatory care and its maindrivers in individuals with HIV infection in Switzerland. In this project of the Swiss HIV Cohort Study(SHCS) we will study the direct HIV and non-HIV related costs and resource use for in hospital andambulatory care of HIV-infected individuals in Switzerland. We explore and assess factors such aslate presentation, duration of HIV infection and others as predictors for high resource use andcosts. This is a pilot and feasibility study where two completely anonymized data sets from theSHCS and claims data from Helsana will be matched with an encrypted method (Bloom filters)with birth dates, gender, and antiretroviral therapy being the matching variables.Start of project: 01.10.2014 – End of project: 30.05.2018

METHODOLOGICAL RESEARCH PROJECTS

Defining “Quality” in Clinical Research – A systematic review and structured framework*The objectives of this study are 1) to systematically review suggested definitions for “quality” inthe context of clinical research taking into consideration the viewpoints of different stakeholders;and 2) to develop a consistent and comprehensive framework of clinical research quality, whichcould later serve as a basis to operationalize and develop a quality assessment/measurement toolof such.Start of project: 01.10.2014 – End of project: 31.03.2018

Epidemiology and publication of discontinued randomised trials; DISCO

DISCO – design features DISCO 2*This study is a matched comparison between discontinued RCTs and completed RCTs. Based onkey characteristics of the trials discontinued due to poor recruitment (i.e. patient population, intervention, comparator, and outcome) we will conduct systematic searches of electronic databases to identify similar RCTs that were completed as planned. We will then analyse the pairsof completed and discontinued RCTs for differences in design features, logistics, and trial conduct.Start of project: 03.02.2014 – End of project: 31.10.2018

Learning from failure – Understanding the mechanisms of trial discontinuation DISCO 2*In a first project we will conduct semi-structured interviews with principal investigators of RCTsdiscontinued for insufficient recruitment and with key stakeholders of clinical research in Switzer-land. A second project will examine health-care RCTs funded by the SNSF to explore whether a ri-gorous selection of trials for funding and monitoring decreases the risk of trial discontinuationincluding potential effects of full versus partial funding. In a third project we will perform an ana-lysis of recruitment patterns from about 500 completed and discontinued RCTs conducted in dif-ferent countries and settings. It will explore whether insufficient recruitment can reliably beidentified at an early stage and determine optimal time points and criteria for the assessment ofrecruitment progress in RCTs.Start of project: 01.12.2013 – End of project: 31.12.2018

ACCOMPLISHED PROJECTS IN 20182

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2 *Project Leadership ± Project Partner

Effects of the Swiss human research legislation on the costs of RCTs*The objectives of this study are to compile a comprehensive list of cost items for the planning andconduct of RCTs (industry and academic settings), to determine the unit costs for listed cost itemsand to evaluate the average/mean total cost of completed RCTs in Switzerland, stratified by sponsor (industry vs. non-industry), and to compare the planning and preparation costs of RCTsin Switzerland before and after the introduction of the Swiss Legislation on Human Research in2014Start of project: 01.07.2015 – End of project: 31.05.2018

Longitudinal evaluation of the accuracy and completeness of clinical trial protocols – evidence for improvement?*The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) were publishedin 2013 and the new Swiss Federal Law on Research in Humans (Humanforschungsgesetz, HFG)came into effect in January 2014. The present project aims to investigate the accuracy and completeness of clinical trial protocols approved by research ethics committees before the introduction of SPIRIT & HFG and thereafter. In addition, we will evaluate the extent of appropria-tely registered protocols before the introduction of SPIRIT & HFG and thereafter (in national or international registries).Start of project: 07.11.2014 – End of project: 31.05.2018

Concordance of treatment effects of observational studies using marginal structural modelsand randomized controlled trials: meta-epidemiological study*Marginal structural models (MSMs) are increasingly used to address confounding issues in biomedical research. This meta-epidemiological study seeks to explore whether modern MSM-based analyses of ‘real world’ observational data can be used to reliably guide health caredecision making.Start of project: 20.03.2013 – End of project: 31.12.2018

„Beschreibende Statistik der Forschung im Geltungsbereich des Schweizer Humanfor-schungsgesetzes (HFG)“ (subproject 1) und „Befragung der Forschenden zur Umsetzung desHFG“ (subproject 2)*Starting January 2016 all applications to research ethics committees (RECs) in Switzerland needto be submitted and managed through a central online portal (BASEC). This project comprises 3parts: 1) A descriptive analysis of the BASEC content (all studies sent to Swiss RECs) for 2016/2017and then yearly updates until 2021; 2) a survey of researchers/principal investigators of studiessubmitted via BASEC in 2017; and 3) to describe research projects for which applicants were uncertain whether they are within the scope of the Human Research Act or not. The project is donein collaboration with the Swiss Clinical Trial Organisation and Cochrane Switzerland.Start of project: 15.12.2017 – End of project: 30.11.2018

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Antivirals for influenza like syndrome: A randomised controlled trial of clinical and cost effectiveness in primary care±Influenza is a highly contagious infection with considerable morbidity, mortality in particular inthe elderly and economic implications. Whether antiviral treatment of patients with flu-like syndromes during influenza seasons is beneficial remains controversial. In this large trial 4500 children and adults from 20 European networks will be randomized to oseltamivir, nitazoxanide(each for 5 days), or usual care. Outcomes of interest are return to normal daily activity and thecost-effectiveness of the interventions. The trial represents work package 4 of the Platform of European Preparedness against Reemerging Epidemics (PREPARE) and is funded by the EU, withCEB representing the Swiss network.Start of project: 01.10.2015 – End of project: 30.09.2018

The application of electronic health records in clinical trial research: A systematic review*Electronic health records (EHRs) may facilitate randomized clinical trials (RCTs), mainly by usingpre-existing data infrastructures for recruitment and outcome assessment and potentially savingcosts, time, and other resources. We perform a systematic review of the literature assessing thecurrent use and value of EHR in clinical trials.Start of project: 15.01.2016 – End of project: 31.06.2018

The agreement of treatment effects from randomized trials using routinely collected data(RCD) or actively collected data: Meta-epidemiologic analysis*To determine whether using RCD sources (such as a disease registry or EHR) to measure outcomesof clinical trials leads to different estimates due to a variability in their data validity, we perform a meta-epidemiological analysis comparing the treatment effects measured by different RCD sources against an active data source (traditional RCT).Start of project: 15.01.2016 – End of project: 31.12.2018

The agreement of treatment effect estimates from rapid reviews using abbreviated literaturesearches and traditional Cochrane reviews: a meta-epidemiological study*The agreement of effect estimates obtained from abbreviated literature searches (as conductedin rapid reviews) and those obtained from extensive searches (as performed in Cochrane or Campbell reviews) is unknown. The objective of this study is to assess differences between treatment effects estimated from abbreviated and extensive literature searches. Our results willsystematically quantify the impact of faster and abbreviated searching on treatment effect estimates across a wide range of Cochrane Systematic Review topics.Start of project: 01.07.2016 – End of project: 31.12.2018

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2 *Project Leadership ± Project Partner

ANESTHESIOLOGY

Systematic review and simulation study of ignoring clustered data in surgical trials*Multiple surgical procedures in a single patient are relatively common and lead to dependent (clustered) data. This dependency needs to be accounted for in study design and data analysis. Asystematic review between 2004 and 2013 was performed to assess how clustered data were handled in RCTs including patients undergoing unilateral or bilateral inguinal hernia repair. Studycharacteristics determining the appropriateness of handling clustered data were extracted. Usingsimulations, various statistical methods accounting for clustered data were compared with an analysis ignoring clustering. Clustering was rarely considered in inguinal hernia trials. The simulations underline the importance of considering clustering as part of the statistical analysisto avoid false positive and false-negative results, and hence inappropriate study conclusions.Start of project: 01.02.2013 – End of project: 31.01.2018

Programmed intermittent epidural bolus technique: external validity of trial results*This retrospective cohort study aims at investigating the effects of Programmed intermittent epidural bolus (PIEB) combined with patient- controlled epidural bolus (PCEA) on maternal motorfunction and labour outcome in a typical trial patient (healthy nulliparous) as compared to non-trial patients (multiparous, non-healthy women). The results of the RCTs on PIEB in regards ofmotor function seem to be generalizable to women not eligible in these trials, but these women(non-trial patients) required a higher time-weighted number and volume of additional rescue top-ups. This higher number and volume of rescue top-ups in non-trial patients suggests that theirlabor is more intense, which should be considered in the dosing scheme for PIEB labor analgesiain non-trial patients.Start of project: 11.02.2015 – End of project: 31.06.2018

HTA REPORTS

HTA report – Assessment of knee arthroscopy for the treatment of degenerative changes*The rate of knee arthroscopies in Switzerland has increased by 20% between 2005 and 2011. Theaims of this report are 1) to assess the clinical effectiveness and safety of therapeutic knee arthroscopy compared to any other treatment in patients with degenerative changes of the knee– irrespective of whether they are primarily due to meniscal damage, osteoarthritis of the knee ora mix of both, 2) to assess the clinical effectiveness and safety of therapeutic knee arthroscopy ininpatient compared to outpatient, 3) to assesses the cost-effectiveness and budget impact of therapeutic knee arthroscopy compared to any other treatment in patients with degenerativechanges of the knee primarily due to meniscal damage and 4) and to compare inpatient versusoutpatient therapeutic knee arthroscopy in patients with degenerative meniscal changes.Start of project: 01.01.2017 – End of project: 13.04.2018

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HIV INFECTION, SWISS HIV COHORT STUDY AND MULTICOHORT PROJECTS

SHCS 805 Prevalence and predictors of potential and contraindicated drug-drug interactionsin patients receiving antiretroviral therapy*Potential drug-drug interactions (DDI) are the most common drug-related problem in ambulatorycare and a growing problem in HIV infection due to increasing comorbidities and age of HIV infected patients. In this study of the Swiss HIV Cohort Study (SHCS) we assess the prevalence ofcontraindicated and potential clinically relevant DDIs and determine major patients and providerrelated predictors of DDIs in patients receiving antiretroviral therapy. Finally, we validate drug dataentered into the new Webmed database of the SHCS with a probability matched patient sampleof claims data of Helsana, the largest Swiss health insurer.Start of project: 01.03.2019 – End of project: 31.12.2019

SHCS 820 HIV and co-morbidity related costs in Switzerland: A large scale data linkagestudy*Studies based on representative data on costs and resource use of chronic conditions in Switzerland are scare. Likewise, in HIV there is a lack of high quality cost data. With the success ofantiretroviral therapy (ART) HIV infection has become a chronic condition but comorbidities dueto cardiovascular diseases, cancer and liver cirrhosis are becoming increasingly important. Therefore, HIV infection is an important and prominent disease to study the cost and consequencesof comorbidity in a condition requiring lifelong care and drug treatment. We propose to investigatehealth resource use and consequences for management of HIV and non-HIV related comorbiditiesby matching claims data from health insurers with data from the Swiss HIV Cohort Study by anonymous privacy preserving linkage.Start of project: 01.05. 2018 – End of project: 30.09.2019

SHCS 832 Estimating the effectiveness of NRTI sparing regimens in patients with limitedtreatment options and then re-estimating as data accrue*Novel NRTI sparing regimens with dolutegravir are already in use within the SHCS. There is no goodevidence that these regimens are better than earlier regimens used to treat NRTI intolerant patients. We will develop a framework based on Bayesian methods for routinely updating estimatesof effectiveness as data accrue. This would provide the best information currently available aboutnovel regimens for clinicians treating patients with limited treatment options. We will: (1) Developan appropriate measure of regimen durability given the information available from the SHCS ; (2)Describe a Bayesian statistical method for estimating the relative effectiveness of novel regimensgiven limited time to event data and for then updating those estimates; (3) Provide up-to-date estimates of the relative durability of novel regimens used to treat NRTI intolerant patients.Start of project: 01.10.2017 – End of project: 31.01.2019

SHCS 835 Optimizing HIV-RNA monitoring in naïve patients initiating cART*Self-reported drug adherence patterns in the Swiss HIV Cohort Study will be analysed in mathematical modeling to understand predictors for non-adherence and optimized monitoringintervals for HIV infected patients on antiretroviral therapy. Modeling will be conducted by information specialists from University of Minnesota and Stanford University. Start of project: 01.04.2019 – End of project: 31.03.2020

ONGOING PROJECTS IN 2018

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Smartphone app and CO self-monitoring for smoking cessation: A randomised controlledtrial nested into the Swiss HIV Cohort Study*This a randomized controlled trial nested in the Swiss HIV cohort comparing the effectiveness ofa smartphone app and carbon monoxide self-monitoring support for smoking cessation. The primary outcome is the combination of self-reported continuous abstinence biochemically verifiedby a carbon monoxide test in-person, with a cut-off of 7 ppm, at 6 months.Start of project: 09.08.2017 – End of project: 31.04. 2020

METHODOLOGICAL RESEARCH PROJECTS

NFP72: Routine Antibiotic Prescription*Antibiotic resistance is a worldwide problem and associated with the direct use of antibiotics inthe population. Most antibiotics are used in primary care for acute respiratory tract infections, although primarily of viral origin, and urinary tract infections (UTI). In a nationwide pragmatic randomized intervention trial we use routinely collected fully anonymised claim data from 4 largehealth insurers covering 40% of insurers in Switzerland and investigate whether routine antibioticprescription feedback in primary care physicians reduce antibiotic use. We will link claim data withnational antibiotic resistance data by anonymized probabilistic record linkage to investigate whehter the intervention affects resistance of bacteria against broad-spectrum antibiotics for URTI.A health economic evaluation will be integrated part of the trial.Start of project: 01.01.2017 – End of project: 30.05.2020

Sinus-Endoskopie zur Diagnose der akuten bakteriellen Rhinosinusitis*Acute rhinosinusitis is one of the most common reasons for consultations and the most commonreason for antibiotic prescriptions in primary care, although the condition is primarily of viral origin.Antibiotic overuse in acute rhinosinusitis is mainly due to the lack to objectively diagnose acutebacterial rhinosinusitis. Endoscopy of the rhinopharynx and collection of diagnostic material fromthe ostium draining the sinus is the most reliable method to diagnose acute bacterial rhinosinusitisbut is only used by specialists (otolaryngologists). We have developed a one-way usable devicethe JGG endoscope® (patent number PA 2016 00657) which can be attached to pocket otoscopesthat allows for the diagnosis of acute bacterial rhinosinusitis in primary care.Start of project: 01.10.2018 – End of project: 30.09.2019

Impact of non-standardized outcome analyses on clinical care of HIV patients: metaepide-miological study*We conduct a meta-epidemiological study evaluating a large number of recently published trialson antiretroviral treatment in HIV. Results are recalculated using various alternative approachesto deal with missing data. Implications on clinical interpretation of the trial results are assessed.We aim to provide healthcare decision makers with an empirical estimate of the impact of non-standardized outcome analyses on clinical care by describing how frequently using a differentapproach would change the clinical interpretation of trial results.Start of project: 01.02.2016 – End of project: 31.01.2019

Routinely collected health data for randomized trials – The RCD for RCT initiative*Large and simple pragmatic mega-trials may be conducted with only a fraction of costs whenusing routinely collected health data (RCD). The RCD for RCT initiative aims on improving how clinical trials are made, driven by a strong believe that most of the problems of randomized clinicaltrial (RCT) evidence are man-made and routine data can be a key to solve many of these issues.Start of project: 01.02.2016 – End of project: open

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Development of a reporting guideline for RCTs using routinely collected data (RCD)*This project assesses the reporting gaps in RCD trials, followed by a stakeholder qualitative processfor the development of a reporting guideline and checklist. The qualitative process will encompassa survey to stakeholders such as clinical researchers, clinicians, publishers and pharmaceutical industry representatives; and we will closely collaborate with the RECORD and CONSORT groups.Start of project: 01.03.2018 – End of project: 31.12.2019

Arthroscopic rotator cuff reconstruction: Development of prediction models for selectedpatient outcomes*.Arthroscopic rotator cuff repair (ARCR) is a cost-effective procedure associated with rapid recoveryof shoulder function and quality of life in most patients. Some patients, however, experience localcomplications or do not recover well. Shoulder stiffness, which occurs in about 10% of patientswithin 6 months after ARCR, is associated with major limitation in the functional integrity of affected persons in everyday activities. The objective of this project was to develop a predictivemodel for the risk of occurrence of shoulder stiffness. Start of project: 07.12.2018 – End of project: 31.12.2019

Coronary syndromes and inflammation: Cysteine-rich angiogenic inducer 61 (Cyr61)±Clinical scores and biomarkers improve risk stratification of patients with acute coronary syndromes. However, little is known about their value in patients referred for coronary angiography. Consecutive patients admitted at four Swiss university hospitals with a diagnosis ofthe acute coronary syndrome were enrolled in the SPUM-ACS Biomarker Cohort between 2009and 2012. Patients were followed at 30 days and 1 year with assessment of adjudicated events including all-cause mortality and the composite of all-cause mortality or non-fatal recurrent myocardial infarction. We know that the Global Registry of Acute Coronary Events (GRACE) riskscore has good predictive accuracy for death or myocardial infarction and allows identification ofhigh-risk patients. Cyr61 (also called CCN1) is a novel biomarker currently evaluated for diagnosticand prognostic performance in addition to the GRACE[1] score. It is shown that Cyr61 is a novelearly biomarker reflecting myocardial injury that improves risk stratification in ACS patients, however, how much benefit we might gain from the incremental value of other biomarkers hsTnT,NT-proBNP, and, hsCRP combined with Cyr61 and GRACE risk score remains unknown. The objective of this project is to compare the result of previous Cyr61 publication by adding theseknown cardiac biomarkers to assess if the incremental value of existing model improves or not.Start of project: 20.10.2017 – End of project: 31.12.2019

Development and validation of an instrument to assess the credibility of putative subgroupeffects in randomized controlled trials and meta-analyses*The overall goal of this project is to provide clinicians, researchers, and decision-makers with a reliable, valid, and functional instrument for assessing the credibility of subgroup effects found inrandomized trials and meta-analyses. In a first step, we will conduct a systematic survey of the methodological literature addressing the conduct and interpretation of subgroup analyses. Wewill identify and summarize currently suggested credibility criteria and the rationale offered forthese criteria: We then will generate a list of potential instrument items and evidence or opinionabout the relative merits of the criteria.Start of project: 13.11.2013 – End of project: 30.04.2019

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Prediction of recruitment in randomized clinical trial*The objectives of this study are 1) to establish a comprehensive sample of randomized clinicaltrials with individual patient recruitment data; and 2) to develop tools to monitor and predict recruitment. The overall goal of this project is to provide clinical research, trial lists, ethics committees and funding bodies with guidance how to effectively improve patient recruitment inclinical studies.Start of project: 01.01.2017 – End of project: 31.12.2019

ONCOLOGY

CEIT – Cancer (Comparative Effectiveness of Innovative Treatments for Cancer)*In this meta-epidemiological study, the approval studies for all cancer drug treatments that wereapproved since the year 2000 will be systematically reviewed and their methods, size, and treatment effects evaluated. We will also evaluate the post-approval generation of clinical evidenceon effects on overall survival, patient-important outcomes, and the most important cancer specificsurrogate outcomes progression-free survival and tumor response. The ultimate goal is to providedecision-makers with guidance to identify early indications, which innovative drugs likely fulfil,the promise of therapeutic success in the long run and which should be used cautiously until moreevidence is generated.Start of project: 01.10.2015 – End of project: open

Risk of non-AIDS defining and AIDS defining malignancies with early versus delayed initiation of antiretroviral therapy: an international multicohort study*The objective of this study is to investigate the relationship between delayed versus early initiationof antiretroviral therapy (ART) and the risks of non-AIDS defining (NADM) and AIDS defining malignancies (ADM). The analysis will be based on data from European cohorts including HIV infected individuals, and more specifically from the Data Collection o n Adverse events of Anti-HIV Drugs (D:A:D) database, a prospective multi-cohort study of HIV-1 positive persons(https://chip.dk/Studies/DAD). The aim of our study is to compare and model different ART initiation strategies in relation to the risk of NADM, ADM and death using state of the art statisticalmethods to adjust for baseline and time-varying confounders.Start of project: 01.07.2018 – End of project: 31.12.2019

Use of heparin for cancer: individual patient data meta-analysis±Systematic reviews of aggregated trial data indicate a reduction in venous thromboembolism ofheparin in cancer patients and provide moderate confidence that a small survival benefit exists.We will perform an individual patient data meta-analysis (IPDMA) to explore the magnitude of thesuggested survival benefit and address whether or not specific subgroups and characteristics ofcancer patients are more likely to benefit from parenteral anticoagulants.Start of project: 01.04.2013 – End of project: 30.06.2019

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ANESTHESIOLOGY

International multicentre validation study of CLASSIC – Classification of Intraoperative Complications*Quantifiable evidence-based methods for reporting complications are needed to improve perioperative patient safety. While there are several validated systems for reporting postoperativecomplications, there are only a few (none prospectively validated) for reporting intraoperativecomplications. Our group developed a definition and classification for intraoperative complicationswithin a Delphi study involving international interdisciplinary experts. As both surgery and anaesthesia may be involved in complications, all patient-related intraoperative complications areconsidered. This current cohort study aims to assess the validity and feasibility of this newly derived classification in an international multicentre cohort study. Providing a well-applicable internationally validated classification system for intraoperative complications is an important contribution to the quality of health care and perioperative patient safety.Start of project: 01.01.2015 – End of project: 01.01.2019

HTA REPORTS

HTA report – Iron therapy for iron deficiency without anaemia*Iron deficiency with no anaemia (IDNA) appears to be associated with different symptoms suchas fatigue or restless legs that may be alleviated by iron therapy. The effectiveness of iron therapyin symptomatic patients with IDNA is unclear and there is no consensus regarding the relevant diagnostic markers and thresholds that should be used to to treat IDNA. The aims of this reportsare: 1) to assess the effectiveness of iron therapy in populations with symptomatic IDNA with asystematic review, 2) to assess diagnostic markers with an individual patient data meta-analysisin population with relevant treatment effect which were identified within the systematic reviewand 3) to assess costs of intravenous versus oral treatment in the populations identified in the systematic review.Start of project: 01.02.2017 – End of project: 30.06.2019

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Undergraduate

University of BaselH.C. Bucher, M. Briel, L.G. Hemkens, B. Kasenda and A.J. Nordmann teach principles of evidence-based medicine, critical appraisal skills, basics in clinical epidemiology and clinicalresearch methodology to medical students in the Bachelor and Master’s program at the University Basel. Total teaching obligations in 2018 were 148 hours. H.C. Bucher and M. Brielcoordinate three teaching blocks in undergraduate medical training (Wissenschaftliche Kompetenz, Patienten Orientierte und Evidenz-basierte Medizin (POEM), and Wissenschafts-monat). Total teaching obligations were 267 hours corresponding to 515 LAS.

ETH Zurich H.C. Bucher has been appointed to set up the Digitale Medicine, clinical research methodologycourse I for the bachelor programme in Medicine, which will start in February 2019.

Postgraduate

1. Giusi Moffa. Statistical tests for categorical data. PhD Program Health Sciences, University ofBasel.

2. Giusi Moffa. Analysis of categorical data: Measures of Agreement. PhD Program Health Sciences, University of Basel.

3. Giusi Moffa. Analysis of categorical data: Associations of binary variables. PhD Program HealthSciences, University of Basel.

4. Giusi Moffa. Practical Session on the analysis of categorical data. PhD Program Health Sciences, University of Basel.

5. Lars Hemkens. An introduction to systematic reviewing: From literature search to meta-analysis. PhD Program Health Sciences, University of Basel.

6. Lars Hemkens. Fundamentals of producing, interpreting and using evidence in health care.MSc & PhD Curriculum in Epidemiology, Swiss TPH, Basel

7. Matthias Briel. Science Club Methods. University of Basel.8. Matthias Briel. Randomized Controlled Trials. Essentials of Health Research Methodology.

Essentials of Health Research Methodology, University of Basel.9. Matthias Briel. An introduction to systematic reviewing: From literature search to meta-

analysis. PhD Program Health Sciences, University of Basel.10. Matthias Briel. Sponsor-Investigator Course. Good Clinical Practice Training, University of

Basel11. Matthias Briel. Certificate of Advances Studies (CAS) for Study nurses / Coordinators. Module

1: Clinical Study Concepts, Basel.12. Matthias Briel. Certificate of Advances Studies (CAS) in Clinical Research II. Module 4: Efficiency

Strategies for Clinical Studies, Basel.13. Matthias Briel. Fundamentals of producing, interpreting and using evidence in health care.

MSc & PhD Curriculum in Epidemiology, Swiss TPH, Basel.14. Matthias Briel. Online Course on Randomized Controlled Trials (HRM 772). Health Research

Methodology MSc & PhD, Basel.15. Salome Dell-Kuster. Bias - Rolle im Studiendesign und in der Studiendurchführung. Research

Lunch Study Nurses, University Hospital Basel.16. Salome Dell-Kuster. Inferential Statistics Populations. European Society of Anaesthesiology

(ESA) Masterclass in Statistics and Research Methodology, Katowice, Poland.

TEACHING

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17. Salome Dell-Kuster. Normality & Transforms (Excercise). European Society of Anaesthesiology(ESA) Masterclass in Statistics and Research Methodology, Katowice, Poland.

18. Salome Dell-Kuster. Proportions - Chi-Aquare & Fisher Exact Tests. European Society of Anaesthesiology (ESA) Masterclass in Statistics and Research Methodology, Katowice, Poland.

19. Salome Dell-Kuster. Diagnostic tests. European Society of Anaesthesiology (ESA) Masterclassin Statistics and Research Methodology, Katowice, Poland.

20. Salome Dell-Kuster. Systematic Review & Meta Analysis. European Society of Anaesthesiology(ESA) Masterclass in Statistics and Research Methodology, Katowice, Poland.

21. Soheila Aghlmandi. Practical Session Meta Analysis in R. Essentials of Health Research Methodology, University of Basel

22. Soheila Aghlmandi. Introduction to Meta Analysis. MSc & PhD Curriculum in Epidemiology,Swiss TPH, Basel.

23. Soheila Aghlmandi. Introduction to Meta Analysis. An Introduction to systematic reviewing:From Literature search to a meta-analysis, University of Basel.

24. Soheila Aghlmandi. Practical Session Meta Analysis. An Introduction to systematic reviewing:From Literature search to a meta-analysis, University of Basel.

Supervision of Master Theses

1. Luzius Angehrn. Faculty of Medicine, University of Basel. Epidemiology of multimorbidity inthe perioperative population and their effect on outcome supervised by S. Dell-Kuster.

2. Sirintip Sricharoenchai. Faculty of Science, University of Basel. Agreement of different sourcesof approval evidence for innovative cancer treatments: a meta-epidemiologic study supervisedby L.G. Hemkens.

Supervision of MD Theses

1. Amar Polutak. Discrepancy in reporting of perioperative complications supervised by S. Dell-Kuster.

2. Laura Gabriel. Programmed intermittent epidural bolus technique: external validity of trial results supervised by S. Dell-Kuster.

PhD Students (Epidemiology)

1. Matthias Briel MD, MSc. Successfully defended his PhD thesis 03.12.20182. Aviv Ladanie. MSc. Evolution of evidence on treatment effects from randomized trials, 2015-

2018. Successfully defended his PhD thesis 20.09.20183. Dmitry Gryaznov. MD, MSc. Longitudinal evaluation of the accuracy and completeness of

clinical trial protocols, 2017-2020.4. Eric Remera. MSc. Evaluating the effectiveness of HIV treatment and preventions in Rwanda,

2018-2021

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5. Hannah Ewald. MSc. Impact of enhanced confounder control methods in non-randomizedcomparative effectiveness research, 2015-2018. Successfully defended her PhD thesis22.03.2018

6. Larsa Gawria. MD. Complications in perioperative care, 2018-20217. Kimberly McCord. MSc. Routinely collected data for randomized trials, 2017-2020. 8. Sabin Nsanzimana. MD, MSc. Linkage to and retention in HIV Care and treatment in the

Rwanda National HIV Program: Optimizing the effectiveness for individual- and community-level outcomes in the era of pre- and on ART in Rwanda, 2015-2018. Successfully defended hisPhD thesis 09.07.2018

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Name Position Employment

Prof. Dr. med. Heiner C. Bucher, MPH Head of Institute 100%

Prof. Dr. med. Matthias Briel, MSc Senior Scientist associated collaborator

PD Dr. med. Salome Dell-Kuster, MSc Senior Scientist 20%

PD Dr. med. Lars G. Hemkens, MPH Senior Scientist associated collaborator

PD Dr. med. Dr. phil. Benjamin Kasenda Senior Scientist associated collaborator

PD Dr. med. Michael Koller, MSc Senior Scientist associated collaborator

Prof. Dr. med. Dr. med. dent. Pedram Sendi, PhD Senior Scientist associated collaborator

James Young, PhD Senior Biostatistician associated collaborator

Giusi Moffa, PhD Senior Biostatistician 80%

Soheila Aghlmandi, PhD Biostatistician 100%

Elisabeth Deutschmann Junior Biostatistician 80%

Dr. rer. nat. Susanne Stampf Biostatistician associated collaborator

Viktoria Gloy, PhD Research Fellow 50%

Dominik Glinz, PhD Research Fellow 100%

Hannah Ewald, PhD MPH Research Fellow 20%

Dr. med. Stefan Schandelmaier Research Fellow associated collaborator

Prof. Dr. med. vet. Laurent Audigé Senior Scientist associated collaborator

Dr. med. Jan Adam Roth Research Associate associated collaborator

Priya Satalkar-Goetz, PhD Research Associate associated collaborator

Dr. med. Ramon Saccilotto, MAS Research Associate associated collaborator

Madeleine Wick, Dipl. Pharm. MPH Study Coordinator associated collaborator

Juliane Rick, Dipl. Biomathematikerin (FH) Data Manager associated collaborator

Dr. med. Dmitry Gryaznov, MSc PhD Student Epidemiology 100%

Kimberly McCord, MSc PhD Student Epidemiology 100%

Dr. med. Sabin Nsanzimana, MSc PhD Student Epidemiology associated collaborator

Eric Remera, MSc PhD Student Epidemiology associated collaborator

Larsa Gawria PhD Student Epidemiology associated collaborator

Sirintip Sricharoenchai Master Student associated collaborator

Diana Grauwiler Clinical Research Manager 60%

Kübra Özoglu, MSc Administrative Assistent 40%

STAFF AS OF 31.12.2018

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Basel Institut ceb für klinische Epidemiologie und BiostatistikUniversitätsspital BaselHebelstrasse 10CH-4031 Basel Telefon: +41 (0)61 265 31 00www.ceb-institute.org

Basel Institute cebfor Clinical Epidemiology and Biostatistics

CEB Basel Institutefor clinical Epidemiology and BiostatisticsSpitalstrasse 12CH-4031 Basel, SwitzerlandTelefon: +41(0)61 265 31 00www.ceb-institute.org

CEB Basel Institutefor Clinical Epidemiology and BiostatisticsSpitalstrasse 12CH-4031 Basel, SwitzerlandTelefon: +41(0)61 556 51 00www.ceb-institute.org