Author Contributions: Drs Jakob and Ruokonen contributed equally as first authors. Drs Ruokonen, Jakob, and Takala had full access to the study data. Dr Takala had the final responsibility for the decision to submit the manuscript. Drs Jakob and Ruokonen served as co–principal investigators and, with Dr Takala, conceived the original idea of the 2 studies.
Study concept and design: Jakob, Ruokonen, Grounds, Sarapohja, Garratt, Pocock, Bratty, Takala.
Analysis and interpretation of data: Jakob, Ruokonen, Sarapohja, Garratt, Pocock, Bratty, Takala.
Drafting of the manuscript: Jakob, Ruokonen, Grounds, Sarapohja, Garratt, Pocock, Bratty, Takala.
Critical revision of the manuscript for important intellectual content: Jakob, Ruokonen, Grounds, Sarapohja, Garratt, Pocock, Bratty, Takala.
Statistical analysis: Jakob, Ruokonen, Sarapohja, Pocock, Takala.
Obtained funding: Jakob, Takala.
Administrative, technical, or material support: Ruokonen, Sarapohja, Garratt, Bratty.
Study supervision: Jakob, Ruokonen, Takala.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. This study was sponsored by Orion Pharma, Espoo, Finland, through research contracts negotiated directly with the participating hospitals. Orion Pharma, Orion Corporation, is the originator of dexmedetomidine. On behalf of Drs Jakob and Takala, a grant and consulting fees were paid to the Bern University Hospital Department of Intensive Care Medicine to cover the costs of performing the study. The department was reimbursed for the authors' travel costs to publication committee meetings. Dr Jakob served as an expert for preparing the regulatory filing of the drug; the money was also paid into a departmental fund. Additionally, the Department of Intensive Care Medicine has, or has had in the past, research contracts with Abbott Nutrition International, B. Braun Medical, CSEM, Edwards Lifesciences Services, Kenta Biotech, Maquet Critical Care, and Omnicare Clinical Research and research and development or consulting contracts with Edwards Lifesciences, Maquet Critical Care, and Néstle. The money is or was paid into a departmental fund; no author received any personal financial gain. The department has received unrestricted educational grants from the following organizations for organizing a quarterly postgraduate educational symposium, the Berner Forum for Intensive Care: Fresenius Kabi, MSD, Lilly, Baxter, Astellas, AstraZeneca, B. Braun, CSL Behring, Maquet, Novartis, Covidien, Mycomed, and RobaPharma. Dr Grounds received a consulting fee from Orion Pharma during planning and execution of the study. He and members of his clinical staff at St George's Hospital received monetary support from Orion for travel to study-related meetings to ensure compliance with the study protocol. His department received payment of a fee per patient recruited to the study, as well as drugs used in the study and support personnel to assist with data input. Dr Ruokonen's institution, Kuopio University, received a grant from Orion to carry out the study, as well as consulting fees and reimbursement of travel funds. Messrs Sarapohja, Garratt, and Bratty were full-time employees of Orion Pharma throughout the period of the project. Their routine travel expenses were reimbursed as part of their employment. Dr Pocock of the London School of Hygiene and Tropical Medicine received a consulting fee from Orion in connection with the study, and his institution received a grant. London School of Hygiene and Tropical Medicine also received a grant for independent statistical review performed by Dr Duolao Wang.
Funding/Support: This study was sponsored by Orion Pharma, Espoo, Finland, through research contracts negotiated directly with the participating hospitals.
Role of the Sponsors: The original idea was presented to the sponsor by Drs Jakob and Takala. The sponsor and the principal investigators designed the study and the statistical analysis plan. Data were collected by the investigators using the electronic data capture system provided by the sponsor. Data collection and quality control were managed by the contract research organization. The database was managed by the sponsor. Primary analysis according to the statistical analysis plan was performed by the statistician of the sponsor (Mr Sarapohja) and was also confirmed by Dr Duolao Wang under supervision of Dr Pocock. Data were interpreted by the publication committee with members from the sponsor company (Messrs Sarapohja, Garratt, and Bratty). Preparation, review, or approval of the manuscript was performed only through the coauthor members of the publication committee; according to the study contracts, the sponsor had the right to comment on the draft, but the publication committee had the final decision, and the decision to submit the manuscript was the responsibility of the senior author.
Independent Statistical Analysis: Analysis was undertaken by Dr Duolao Wang (Medical Statistics Department, London School of Hygiene and Tropical Medicine, London, United Kingdom) under the supervision of Dr Pocock, Medical Statistics Department, London School of Hygiene and Tropical Medicine. Full access to all of the data used in the study was provided and an independent analysis of the primary and secondary end points reported in this article was performed by repeating the analyses and verifying P values and 95% confidence intervals. Consistency between the objectives set out in the protocol, the prespecified statistical analysis plan, and results of the statistical analysis produced by the sponsor was verified. No discrepancies were found. Drs Jakob, Ruokonen, and Takala also had full access to the data and performed the analyses independently from those of the sponsor. The results reported from these independent analyses were identical to those of the sponsor.
MIDEX Study Group Members: Belgium: Brussels: H. Spapen (UZ Brussel); J-L. Vincent (Université Libre de Bruxelles–Erasme University Hospital); Gent: K. Colpaert (Universitaer Ziekenhuis Gent); Liege: B. Lambermont (Department of Medicine, University Hospital of Liege). Estonia: Tallin: U. Kivistik (North Estonia Medical Centre Foundation); A. Saar (East Tallin Central Hospital); V. Toome (North Estonian Medical Centre); Tartu: K. Tamme (Tartu University Hospital). Finland: Tampere: J. Tenhunen (Tampere University Hospital); Oulu: T. Ala-Kokko (Oulu University Hospital). France: Paris: J-D. Chiche (Groupe Hospitalier Cochin); P. Montravers (Hôpital Bichat-Claude Bernard); Angers: A. Mercat (Centre Hospitalier Universitaire d’Angers); Argenteuil: H. Mentec (Centre Hospitalier Victor Dupouy); Grenoble: J-F. Timsit (Centre Hospitalier Universitaire de Grenoble); La Roche sur Yon: J. Reignier (Service de Réanimation, CHD Les Oudairies); Lille: F. Saulnier (Hôpital Albert Calmette); Limoges: A. Dugard (Centre Hospitalier Universitaire de Limoges); Orléans: T. Boulain (Centre Hospitalier Régional d’Orléans, Hôpital de La Source); Poitiers: R. Robert (Centre Hospitalier Universitaire de Poitiers); Tours: E. Mercier (Centre Hospitalier Régional et Universitaire–Hôpital Bretonneau). Germany: Bonn: C. Putensen (Universitätsklinikum Bonn); Greifswald: M. Grundling (Universitätsklinikum Greifswald); Tübingen: K. Unertl (Universitätsklinikum Tübingen). Netherlands: Zwolle: F. Snellen (Isala Klinieken); Amsterdam: A. Beishuizen (VU Medisch Centrum); Apeldoorn: P. Spronk (Gelre Hospital–Apeldoorn); Breda: B. van der Meer (Amphia Ziekenhuis); Dordrecht: A. Koopman-Van Gemert (Albert Schweitzer Hospital); Haarlem: N. Fennema (Kennemer Gasthuis); Tilburg: B. Speelberg (St Elisabeth Ziekenhuis); Venlo: N. Foudraine (Viecuri Medical Centre). Norway: Oslo: S. Walter and E. Helset (Ulleval University Hospital); R. Lovstad (Oslo University Hospital–Aker); A. Stubhaug (Oslo University Hospital, Rikshospitalet); Bergen: A. Guttormsen (Haukeland University Hospital). Switzerland: Bern: S. Jakob (Bern University Hospital [Inselspital] and University of Bern); Winterthur: A. Haller (Kantonsspital Winterthur); Zürich: M. Maggiorini (Universitätsspital Zürich). United Kingdom: Birmingham: G. Perkins (MIDRU, Heart of England NHS Foundation Trust); A. Whitehouse (Selly Oak Hospital); Plymouth: P. MacNaughton (Derriford Hospital).
PRODEX Study Group Members: Belgium: Aalst: I. Demeyer (Onze-Lieve-Vrouw, Ziekenhuis); Genk: R. de Jongh (Ziekenhuis Oost Limburg, Schiepse Bos); Gent: K. Colpaert (Universitaer Ziekenhuis Gent). Finland: Kuopio: I. Parviainen (Kuopio University Hospital); Espoo: T. Oksanen (HUCH, Jorvi Hospital); Helsinki: M. Kaukonen (HUCH, Meilahti Hospital); Joensuu: M. Reinikainen (North Karelia Central Hospital); Lahti: P. Loisa (Päïjät-Häme Central Hospital); Lappeenranta: S. Hovilehto (South Karelia Central Hospital); Seinäjoki: K. Saarinen (Seinäjoki Central Hospital); Tampere: J. Tenhunen (Tampere University Hospital). Germany: Berlin: C. Spies (Charité–Universitätsmedizin Berlin); Erlangen: J. Schuttler (Universitätsklinikum Erlangen); Frankfurt am Main: K. Zacharowski (Klinikum der J. W. Goethe-Universität); Giessen: T. Menges (University of Giessen and Marburg); Halle: J. Soukup (Universitätsklinikum Halle); Heidelberg: J. Motsch (Universitätsklinikum Heidelberg); Homburg/Saar: T. Volk (Universitätsklinikum des Saarlandes); Leipzig: U. Kaisers (University Leipzig, Medical Faculty); A. Sablotzki (Klinikum St Georg); Tübingen: K. Unertl (Universitätsklinikum Tübingen); Wetzlar: J. Engel (Klinikum-Wetzlar-Braunfels); Netherlands: Breda: B. van der Meer (Amphia Ziekenhuis); Hertogenbosch: F. Rozendaal (Jeroen Bosch Ziekenhuis); Hoorn: P. Knüpfer (Westfries Gasthuis); Tiel: M. van Iperen (Rivierenland Hospital). Russia: Kemerovo: E. Grigoryev (M. A. Podgorbunsky Municipal Clinical Hospital); Krasnodar: Zabolotskikh (Municipal Hospital No. 2, Krasnodar Diversified). Switzerland: Bern: S. Jakob (Bern University Hospital [Inselspital] and University of Bern). United Kingdom: London: R. Grounds (St George's Hospital); Bury St Edmunds: J. Cardy (West Suffolk Hospital NHS Trust); Edinburgh: T. Walsh (Edinburgh Royal Infirmary); Leeds: A. Mallick (Leeds General Infirmary); Livingston: L. Morrison (St John's Hospital).
Previous Presentation: The main results were presented orally at the 31st annual International Symposium on Intensive Care and Emergency Medicine (ISICEM); March 22-25, 2011; Brussels, Belgium.
Additional Contributions: We thank Jeannie Wurz, BA, a medical editor employed by the Department of Intensive Care Medicine at the Bern University Hospital, for editorial assistance. She did not receive compensation besides her salary.