Leitfaden für die Antragstellung Modul 1 Forschungsverbünde Nationales Forschungsnetz zoonotische Infektionskrankheiten vom

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1 Leitfaden für die Antragstellung Modul 1 Forschungsverbünde Nationales Forschungsnetz zoonotische Infektionskrankheiten vom Inhaltsverzeichnis Mustervorlagen für den Verbundantrag A Mustervorlage für die übergreifende Darstellung des Verbundes (Mantelantrag) 2 (max. 10 Seiten) B Mustervorlage für ein Teilprojekt (max. 5 Seiten) 5 C Mustervorlage für Tierversuche in einem Teilprojekt (zusätzlich 3 Seiten) 7 D Mustervorlage für eine klinische Studie (max. 12 Seiten) 8 E Mustervorlage für eine epidemiologische Studie (max. 10 Seiten) 17 Der Antrag für einen Forschungsverbund muss alle Informationen beinhalten, die für eine abschließende Bewertung erforderlich sind. Er muss aus sich heraus, ohne Lektüre der zitierten Literatur, verständlich sein. Mit Blick auf die internationale Begutachtung wird empfohlen, die Anträge in englischer Sprache abzufassen. Die Anträge werden von einem internationalen Begutachtungsgremium bewertet, welches Empfehlungen an den Förderer ausspricht. Anträge, die den Vorgaben des Leitfadens nicht entsprechen bzw. die die Vorgabe bezüglich der Seitenzahl überschreiten, können möglicherweise nicht berücksichtigt werden. Der Verbundkoordinator oder die Verbundkoordinatorin stellt für den Verbundantrag EIN PDF- Dokument zusammen. Dieses enthält den Mantelantrag und die Teilprojekte nach den Vorgaben dieses Leitfadens. Weitere Anlagen, wie beispielsweise Lebenslauf oder Letter-of- Intent, sind nicht zugelassen. Der Antrag ist in gedruckter und elektronischer Form bis zum auf dem Postweg in 20 gedruckten Exemplaren sowie einem PDF-Dokument auf CD vorzulegen. Die elektronische Version des Antrages sollte nicht größer als 4 MB sein, damit sie per verschickt werden kann. Eine Vorlage des Antrags per oder Fax allein ist nicht möglich. Die Anträge sollen eingereicht werden beim DLR Projektträger Gesundheitsforschung Stichwort Zoonosen Heinrich-Konen-Str Bonn Es wird dringend empfohlen, zur Antragsberatung mit dem Projektträger Kontakt aufzunehmen. Weitere Informationen und Erläuterungen sind dort erhältlich. Kontaktpersonen sind: Dr. Ursula Kopp (Tel.: , ursula.kopp@dlr.de) und PD Dr. Barbara Junker (Tel.: , Barbara.Junker@dlr.de).

2 Mustervorlagen für den Verbundantrag Hinweis: Alle unten dargestellten Mustervorlagen zur Erstellung der Antragsskizze können auch als editierbare Word-Datei hier heruntergeladen werden. Formatvorgabe für den Antrag: DIN A4, 11 Punkt Arial, 1-zeilig, doppelseitig A Mustervorlage für die übergreifende Darstellung des Verbundes (Mantelantrag) Consortium Application within the Funding Activity Nationales Forschungsnetz zoonotische Infektionskrankheiten Zur Darstellung des gesamten Verbundes sowie der übergeordneten Planung und Ziele darf die maximale Seitenzahl zehn Seiten (zzgl. einer Seite für Synopsis ) nicht übersteigen. Die angegebene Seitenzahl beinhaltet die zitierte Literatur. Stellen Sie darüber hinaus die im Verbund geplanten einzelnen Forschungsprojekte (Teilprojekte) dar. Für den Fall, dass Tierversuche bzw. klinische oder epidemiologische Studien geplant sind, sind diese separat anhand der angehängten, jeweiligen Formatvorlagen darzustellen. Alle Dokumente fügen Sie bitte in einem Antrag zusammen. Im Falle klinischer oder epidemiologischer Studien wird dringend empfohlen, einschlägige Experten, wie z.b. ein KKS oder eine epidemiologisch ausgewiesene Einrichtung einzubinden. Bitte nutzen Sie zur Antragstellung die vorgegebene Gliederung. Die Eintragungen in kursiver Schrift sind als Hinweise für die Antragerstellung gedacht und sind vor Antragseinreichung zu löschen. Bitte machen Sie zu jeder Überschrift eine Eintragung. SYNOPSIS (Tabellarische Zusammenfassung; max. 1 Seite) Applicant/ Coordinator (nur eine Person angeben, die den Verbund koordiniert und Ansprechpartner des PTs ist) Titel, Vorname, Name Institut/Klinik/Fachbereich Einrichtung Dienstanschrift Dienstliche Telefon- und Faxnummer, -Adresse Title of the Consortium Englischer und deutscher Titel des Verbundes Acronym of the Abkürzung/ Kurzwort für den Verbund Consortium Addressed zoonotic Benennen Sie kurz die zoonotische Infektionskrankheit beim infectious disease and Menschen und die entsprechenden Erreger, die im Verbund pathogens bearbeitet werden. Structure of the Consortium Summary of the Proposal Requested Funding for the Consortium Requested Funding Period Benennen Sie die beteiligten Einrichtungen/ Verbundpartner, nennen Sie nur Projektleiter, Institution, Ort und Sektor (z.b. Humanmedizin, Veterinärmedizin, Lebensmittel, ÖGD Humanmedizin, so dass der One Health-Ansatz deutlich wird) Bitte fassen Sie die wissenschaftlichen Ziele Ihres Verbundes kurz zusammen und verdeutlichen dabei den One Health- Ansatz und die Anwendungsrelevanz für den ÖGD (max Zeichen inkl. Leerzeichen). Welche Instrumente und Methoden sollen entwickelt werden? Gesamtsumme (BMBF-Anteil inklusive Projektpauschale oder Gemeinkosten; bei KMU Förderquote 50%) für den gesamten Verbund für die beantragte Förderzeit in Max. mögliche Förderdauer sind 5 Jahre. 2

3 1. Current Situation 1.1 The medical problem Welche zoonotische Infektionskrankheit beim Menschen soll im Verbund bearbeitet werden? Wie stellt sich die Versorgungssituation für betroffene Patientinnen und Patienten dar? Wie sehen aktuell verfügbare Präventions-, Diagnostik- und Behandlungsmöglichkeiten aus? Welches konkrete Problem in der Praxis soll durch den Verbund bearbeitet werden? 1. 2 Relevance of the topic for public health Welche gesundheitspolitische Relevanz hat/ haben die adressierte(n) Infektionskrankheit(en) Welche Relevanz haben die zoonotische Infektionskrankheit und die pathogenen Erreger für den ÖGD? 1.3 The need for interdisciplinary research (One Health-approach) Begründung des spezifischen, interdisziplinären Forschungsbedarfes? Wie wird der One Health-Ansatz umgesetzt? Begründung der beteiligten Partner! 2. Own Previous Work and Infrastructures Welche eigenen Vorarbeiten wurden von den Verbundpartnern im adressierten Themengebiet erbracht? Welche vorhandenen Infrastrukturen (z.b. Daten und Materialbanken, Tiermodelle) können genutzt werden? Auf welche zusätzliche Expertise (ggf. auch externe Partner) kann der Verbund zur Erreichung seiner Ziele zurückgreifen? 3. Aims and Structure of the Consortium 3.1 Aim of the consortium Was sind die Ziele des Verbundes? Welche wissenschaftlichen Fragestellungen sollen bearbeitet werden? Welche Methoden und Instrumente sollen entwickelt werden? Die dem Forschungskonzept zugrunde liegenden Forschungshypothesen sollen als Schirm für die Verbundarbeit klar formuliert werden. 3.2 Structure of the consortium Wie ist der Aufbau des Verbundes geplant? Wie soll sich die Zusammenarbeit im Verbund gestalten? Welche Partner beteiligen sich mit welchen Aufgaben an dem geplanten Verbund? Beachten Sie, dass der One Health-Ansatz deutlich wird! Gibt es eine Zusammenarbeit mit Partnern (ggf. auf nationaler/ internationaler Ebene) außerhalb des Verbundes? Nutzen Sie für die Darstellung bitte auch die folgende Tabelle, die Sie ergänzen können: Name Affiliation Responsibility/ Role/ Contribution Sub- Project no Work Plan Stellen Sie den Arbeitsplan im Verbund kurz dar: Was soll konkret gemacht werden? Wie sollen die oben genannten Ziele erreicht werden? Für die geplanten Teilprojekte ist der inhaltliche Bezug untereinander und zum wissenschaftlichen Gesamtkonzept herzustellen und ihre Auswahl zu begründen. Die Kooperationen zwischen den Teilprojekten mit Angaben zu Art, Umfang und Zweck sind zu 3

4 erläutern. Zur Verdeutlichung des One Health-Ansatzes im Verbund und der Zusammenarbeit ist ein Organigramm empfehlenswert. Nutzen Sie für die Darstellung bitte auch die folgende Tabelle, die Sie ergänzen können: Sub- Project no. Animal study Cohort sudy Method Material Aim DURC 1 mice potential (yes/no) 3.4 Added value of the joint work Welcher Mehrwert ergibt sich aus der Zusammenarbeit im Verbund gegenüber einem Einzelvorhaben? Wie gestaltet sich der Nutzen des Verbundes aus Sicht der Forschung? Was können die zu erwartenden Ergebnisse aus dem Verbund für die Anwendung durch den ÖGD beitragen? 4. Financial Summary and Time Schedule Die zeitliche und finanzielle Planung sollte in einem Balkendiagramm dargestellt werden. Das unten angefügte Muster ist als Beispiel zu verstehen. Die Darstellung kann hiervon abweichen. Bei der Gesamtsumme für jedes Teilprojekt ist an Universitäten die 20%-Projektpauschale und bei Institutionen sind die Gemeinkosten einzurechnen. Year 1 Year 2 Year 3 Year 4 Year 5 Funding Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 (Mio. ) Subproject 1 Title of the subproject 0,3 Subproject 2 Title of the subproject 0,8 Subproject 3 Title of the subproject 1,2 Subproject 4 Title of the subproject 1,1 Subproject 5 Title of the subproject 0,7 Subproject 6 Title of the subproject 0,5 4,6 5. References 1 Die Prüfung eines möglichen DURC-Potentials ist Gegenstand des Begutachtungsprozesses. Als Orientierung wird auf die nachstehende Definition verwiesen: Als besorgniserregende Biosecurity-relevante Forschung (Dual Use Research of Concern, DURC) werden lebenswissenschaftliche Arbeiten verstanden, bei denen anzunehmen ist, dass sie Wissen, Produkte oder Technologien hervorbringen, die unmittelbar von Dritten missbraucht werden können, um die öffentliche Gesundheit oder Sicherheit oder die natürlichen Lebensgrundlagen zu bedrohen (siehe Stellungnahme des Deutschen Ethikrates zur Biosicherheit (2014), S

5 B Mustervorlage für ein Teilprojekt Application for a Research Project within the Consortium xy Beschreiben Sie die einzelnen Teilprojekte (max. 5 Seiten pro Teilprojekt) näher. Stellen Sie dabei u. a. die Bedeutung des Projektes für den Verbund dar. Project No. Title Principal Investigator Contribution to the One Health approach Abstract Name, Institution max. 300 words 1 Working hypothesis and Research question(s) Erläutern Sie bitte auch den Beitrag dieses Projektes zur Gesamtthematik des Verbundes. 2 Own previous work and publications Beschreiben Sie kurz die Vorarbeiten mit Bezug zu diesem Projekt und geben Sie dazu max. 5 einschlägige Publikationen an. 3 Work plan including milestones Beschreiben Sie das Arbeitsprogramm mit Zeitschiene und Meilensteinen. Falls das Teilprojekt DURC-Potential hat, nehmen Sie bitte dazu Stellung. Wenn Tierversuche durchgeführt werden, verwenden Sie bitte zusätzlich die Mustervorlage C. 4 Contribution to the consortium Mit welchen Partnern im Verbund arbeiten Sie wie zusammen? Warum muss dieses Projekt in diesem Verbund durchgeführt werden? 5 Quality assurance, standardization, data sharing Stellen Sie die Maßnahmen zur Qualitätssicherung dar. 6 Ethical and legal and considerations Kurze Auflistung etwaiger ethischer und rechtlicher Gesichtspunkte (z.b. Ethikvoten, Tierversuchsgenehmigung, Datenschutz) deren Regelung vor Vorhabenbeginn erfolgen muss. 7 Key references Geben Sie bitte maximal zehn Publikationen an. 8 Financial summary 5

6 Personnel for 5 years Position / Salary Group Total Budget Duration (months) Tasks / Justification Other resources for 5 years Type Total Budget Specification / Justification Consumables Animal costs Equipment Travel Other Sum: Total Budget: Institutional Overhead: Sum: Requested Budget (50% BMBF-share for SME) 6

7 C Mustervorlage für Tierversuche in einem Teilprojekt Unterpunkt zum Punkt 3 Work plan and milestones: Wenn in einem Teilprojekt Tierversuche durchgeführt werden, nehmen Sie bitte Stellung zu den folgenden Punkten, die sich auf die ARRIVE Guidelines 2 beziehen oder begründen Sie, warum diese Punkte nicht beachtet werden müssen. Für diese Unterpunkte können drei zusätzliche Seiten eingefügt werden Animal studies Background and objectives: Explain the experimental approach and rationale; and how the animal model being used can address the scientific objectives, explain the study s relevance to human biology. Methods: a. Study design (number of experimental and control groups, steps to minimise the effects of subjective bias, experimental unit). b. Experimental procedures (drug formulation and dose, anesthetic and surgical procedures, equipment How, When, Where, Why); c. Experimental animals (species, strain, sex, developmental stage, age, weight, source of the animals, genetic modification status, etc.); d. Housing and husbandry (type of facility e.g. specific pathogen free [SPF]; type of cage or housing; bedding material; number of cage companions, type of food, access to food and water, environmental enrichment etc.) e. sample size specify the total number of animals used in each experiment, and the number of animals in each experimental group; provide details of any sample size calculation used. Indicate the number of independent replications of each experiment, if relevant. f. Allocating animals to experimental groups (details of how animals were allocated to experimental groups, including randomisation or matching if done; order of treatment and assessment) g. Experimental outcomes (define the primary and secondary experimental outcomes assessed e.g. cell death, molecular markers, behavioral changes) h. Statistical methods provide details of the statistical methods used for each analysis. specify the unit of analysis for each dataset (e.g. single animal, group of animals). describe any methods used to assess whether the data met the assumptions of the statistical approach. 2 The ARRIVE Guidelines: Animal Research: Reporting of In Vivo Experiments. Originally published in PLOS Biology, June 2010 ( 7

8 D Mustervorlage für eine klinische Studie Application for a Clinical trial within the Consortium xy The description of exploratory clinical trial should not exceed 12 pages (including references, excluding financial table). Please replace the text in italics with your information. 1. STUDY SYNOPSIS APPLICANT/COORDINATI NG INVESTIGATOR TITLE OF STUDY CONDITION OBJECTIVE(S) INTERVENTION(S) KEY INCLUSION AND EXCLUSION CRITERIA OUTCOME(S) STUDY TYPE In case of multiple applicants the principal investigator/coordinating investigator 3 of the trial who will assume responsibility for conducting the clinical trial, should be listed first. First name, last name, academic title Employment status Date of birth, nationality Institution and department (complete name) Postal address Telephone Fax address The title of the trial (not exceeding 140 characters) should be as precise as possible. The medical condition being studied (e.g. asthma, myocardial infarction, depression). Which principal research questions are to be addressed? Specify clearly the primary hypotheses of the trial that has to be confirmed. Which parameter is missing for the conduction of a confirmatory study? Description of the experimental and the control treatments or interventions as well as dose and mode of application. For diagnostic tests or procedures the index test and the reference procedure (gold-standard) should be described. Experimental intervention / index test: Control intervention / reference test: Follow-up per patient: Duration of intervention per patient: Experimental and/or control off label or on label in Germany: if applicable Key inclusion criteria: Key exclusion criteria: Primary efficacy endpoint: Key secondary endpoint(s): Assessment of safety: e.g randomized/non-randomized, type of masking (single, double, observer blind), type of controls (active/placebo), parallel group/cross-over, prognostic, diagnostic 3 "Investigator" as defined in the harmonised Guideline for Good Clinical Practice of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH GCP) ( This definition should be used accordingly for non-drug trials/studies: (1.34 Investigator) A person responsible for the conduct of a clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator. (1.19 Coordinating investigator) An investigator assigned the responsibility for the coordination of investigators at different centres participating in a metacentre trial. 8

9 STATISTICAL ANALYSIS SAMPLE SIZE TRIAL DURATION CONDUCTING CENTRE Efficacy / test accuracy: Description of the primary efficacy / test accuracy analysis and population: Safety: Secondary endpoints: To be assessed for eligibility (n = ) To be allocated to trial (n = ) To be analysed (n = ) First patient in to last patient out (months): Duration of the entire trial (months): Recruitment period (months): Name and address of the conducting centre 1.1 Summary Give a summary of the main aspects of the project; (max characters incl. blanks). 1.2 Intervention scheme/trial flow Describe the intervention scheme and give a schematic diagram (flow chart) of design, procedures and stages. 1.3 Frequency and scope of study visits What is the proposed frequency and scope of study visits and, if applicable, the duration of post-trial follow-up? Please also give a schematic diagram. 2. THE MEDICAL PROBLEM Which medical problem is to be addressed? What is the novel aspect of the proposed trial? Which principal research questions are to be addressed? Bring them into order indicating major and minor motivations/starting hypotheses of the investigation planned and emphasize the missing link for the performance of a confirmatory study. 2.1 Rationale for the trial/evidence Substantiate your starting hypothesis for the trial. What is the rationale for the intervention? Are there any case reports or treatment attempts published? What is the relevance of their results? Please give details of your search strategy for existing information (databases, search terms, limits). This should both detail the background of the starting hypotheses and the feasibility of the trial. 2.2 The need for a trial What impact will the results have on clinical practice or understanding of the proposed intervention or underlying disease? How will a) the individual patient and b) society/science benefit from the trial? Also detail potential economic impact. 2.3 Strategies for data handling and the dissemination of results Describe the implementation and the quality control of the data management, curation and longterm preservation for future reuse. Please regard existing standards and data repositories where appropriate. Please describe how you plan to disseminate the results. 3. JUSTIFICATION OF DESIGN ASPECTS Please do provide justifications and do not only list the respective parameters. 3.1 Control(s)/comparator(s) Justify the choice of control(s)/comparison(s): Is placebo acceptable? Is there a gold standard? Which trials establish efficacy and safety of the chosen control regimen? What is the rationale for the units, cut off and/or categories? 9

10 3.2 Dose, mode and scheme of intervention Justify the dose, the mode and the scheme of the intervention. How does the intervention compare to other interventions for the same condition? What is the rationale for the units, cut off and/or categories? 3.3 Additional treatments Please describe the medication(s)/treatment(s) permitted (including rescue medication) and not permitted before and/or during the trial, if applicable. 3.4 Inclusion/exclusion criteria Justify the population to be studied. Please include information regarding representativeness (gender and age) and the potential to generalize the results. 3.5 Outcome measures Term and describe the crucial clinical data collected during the trial. Define and justify the endpoints chosen: Are there other trials or guidelines that have utilized or discussed this endpoint? What is the clinical relevance of the endpoint for the participant and the disease? Justify appropriateness and limitations of alternative endpoints, if applicable. Determination of primary and secondary measures How will primary and secondary endpoints be derived from actual measurements, and how do they impact the statistical analysis? 3.6 Methods against bias Is randomisation feasible? Which prognostic factors need to be regarded in the randomisation scheme and the analysis? What are the proposed practical arrangements for allocating participants to trial groups? In case of a multicentre trial: Will trial site effects be considered in randomisation? Is blinding possible? If blinding is not possible please explain why and give details of alternative methods to avoid biased assessment of results (e.g. blinded assessment of outcome). For diagnostic trials: what is the training and expertise of persons executing and reading the index tests and the reference standards. 3.7 Proposed sample size/power calculations What is the proposed sample size and what is the justification for the assumptions underlying the power calculations? Include a comprehensible, checkable description of the power calculations and sample sizes detailing the outcome measures on which these have been based for both control and experimental groups; give event rates, means and medians, the software used for sample size calculation etc., as appropriate. Justify the size of difference that the trial is powered to detect, or in case of a non-inferiority or equivalence study, the size of difference that the trial is powered to exclude. Give evidence / references for the estimated effect size. It is important that the sample size calculations take into account anticipated rates of non-compliance and losses to follow up. Compliance/Rate of loss to follow up Provide details for assumptions on compliance issues. On what evidence are the compliance figures based? What is the assumed rate of loss to follow up? On what evidence is the loss to follow up rate based? How will losses to follow up or non-compliance be handled in the statistical analysis? 3.8 Feasibility of recruitment What is the evidence that the intended recruitment rate is achievable? Demonstrate conclusively the potential for recruiting the required number of suitable subjects (the best piece of evidence being pilot studies and preceding trials in a similar population or patient registrations from your institution). In case of a multicentre trial: Show justification of numbers of eligible patients per trial site in a table. The recruitment plan should show the intended recruitment including the criteria for the selection of trial sites. 10

11 3.9 Stopping rules Please specify the stopping rules or discontinuation criteria a) for the individual patient and b) for the whole trial (if applicable). In case of a multicentre trial: Please specify rules for closing participating centres, which fail to include the estimated number of patients. 4. STATISTICAL ANALYSES What is the proposed strategy of statistical analysis? If multiple hypotheses are foreseen for statistical testing: What is the procedure to ensure Type I error control and what will be the primary data analysis set (e.g. ITT-population in case of superiority RCT). What is the strategy for analysing the primary outcome? If applicable, how will multiple primary end points be analysed statistically? If interim analyses are planned, please specify. Are there any subgroup analyses? How will missing data and subjects withdrawn from the trial be handled statistically? What are the methods for calculating test reproducibility in diagnostic trials? 5. ETHICAL CONSIDERATIONS Give a description of ethical considerations relating to the trial (assessment of risks and benefits, care and protection for research participants, protection of research participants confidentiality, informed consent process). 6. QUALITY ASSURANCE AND SAFETY 6.1 Quality assurance/monitoring What are the proposed measures for quality assurance? Which institution will perform the monitoring? Which SOPs will be utilized? Describe and justify the monitoring strategy (percentage of source data verification, number of monitor visits per trial site). Please note: The BMBF will insist on the conduct of pre-trial visits before trial start by independent bodies. Please make sure to include this as a milestone into the time plan and into the budget. The results of the monitoring visits should be documented and reported back to the BMBF. Note that insufficient results of pre-study visits may lead to discontinuation of funding. 6.2 Safety Please comment on the planned supervision of the trial (DSMB - data safety and monitoring board); give name and affiliation of independent DSMB members. Arrangements for the management of the trials will vary according to the nature of the study proposed. However, all should include an element of expert advice and monitoring, that is entirely independent of the principal/coordinating investigator and the medical institution involved. This will normally take the form of a scientific advisory board/trial steering committee (TSC) and/or an independent data safety and monitoring committee (DSMB). It is recognised that these arrangements may not always be appropriate and the committees needed may vary according to the nature of the study. Thus, the arrangements for supervision should be detailed and justified. The role of these committees can comprise to monitor and supervise the progress of the trial (including the safety data and the critical efficacy endpoints at intervals), to review relevant information from other sources, to ensure adherence to protocol, to consider interim analyses, to advise whether to continue, modify or stop a trial and provide the funding organisation with information and advice. Applicants should submit their proposed arrangements for overseeing of the trial and a suggested membership for the committee(s). A minimum of 3 members should be named. List under REFERENCES (max. ½ page) 11

12 8. TRIAL TIMELINE FLOW As funding by BMBF will critically depend on the study progression according to milestones, please provide a diagram reflecting preparation, initiation, recruitment, follow-up and data cleaning/analysis. An example of such a diagram is given below. 9. LIST OF PARTICIPANTS INVOLVED IN THE TRIAL Trial sponsor Trial management # Name Affiliation Responsibility/Role Signature Trial statistician # Name Affiliation Signature Trial supporting facilities (central laboratories, pharmacies etc.) # Name Affiliation Responsibility/Role Recruiting centre (please provide signature on declaration of commitment) # Name Affiliation (only institution and city, no complete address) Expected no. of patients recruited for the complete trial sum of recruited patients Σ = Data Monitoring and Safety Board (DMSB) # Name Affiliation (only institution and city, no complete address) Other participating groups / bodies (e.g. steering committee in international trials) # Name Affiliation Responsibility/Role Review of trial protocol (who will review and finalize the protocol? Please refer to numbers above and/or include others) # Name Affiliation (only institution and city, no complete address) 10. FEASIBILITY 10.1 Previous work Include a list of maximum 5 publications by the principal/coordinating investigator published within the last five years (only the results of clinical trials). 12

13 10.2 Staff and institution s contribution (Grundausstattung) Please indicate name, academic titles and employment grade of participating scientists and the number of technical employees who - without being paid through the funding applied for - will be working on the project. Please list separately the persons paid by the institution s basic funding and those paid from other grants Supporting infrastructure of the medical institution(s) The BMBF expects appropriate support by the institution(s). Please indicate the resources available at your medical institution: existing trial-specific supporting facilities previous experience with the conduct of clinical trials in accordance with GCP possibilities for the training of trial staff 10.4 Declarations of commitment of the conducting centre(s) Please use the template provided to declare the commitment of the participating centre(s) (including the centre of the principal investigator). The template is to be signed personally by the investigator at the respective site (as named in the list of participants involved in the trail; see heading 9.). Do not submit facsimiles. Name of investigator: Institution: Information on the exploratory clinical trial (according to the full proposal) Trial title: Inclusion criteria: Exclusion criteria: recruitment period (months): Strategy for the determination of recruitment figures How many patients with the condition specified above have you seen in your institution during the last 12 months? How many of these patients would fulfil the inclusion criteria of the above mentioned trial? How many of these patients would approximately agree to participate in the above named clinical trial per year? How many patients will approximately be recruited during the entire trial? Which source did you use for the estimation of potential participants in the above named clinical trial? Individual estimation Hospital data management system Patient registry Others If others: please specify Are there any other ongoing clinical trials/ projects competing for the same patients? If yes: How will this affect recruitment for the above-named clinical trial? yes no 13

14 Commitment to participate I hereby agree to participate in the above-named clinical trial and support the trial by recruiting patients. Date/ Signature Conflicts of Interest I hereby declare that I have no conflict of private, economical or financial interests with regard to the above mentioned clinical trial and the investigational drugs that will be used. Date/ Signature 11. FINANCIAL DETAILS OF THE TRIAL 11.1 Commercial interest Please justify why this trial should be funded by a public funding agency. Describe any potential commercial interest of a company in the results of the trial or explain why no such interest exists. Note that direct commercial interest of a company in the results of the trial precludes funding Financial summary Indicate total duration of the trial, the period of time for which funding is requested and when funding should begin. Funding by BMBF may be granted for the total period necessary to conduct the trial. The overall expenditure should be summarized in the table below (maximum 1 page). Indicate amounts in in the column Total ( ). General annotations: Funds can only be granted for research activities. Do not include patient care costs. Where necessary, itemise more detailed justifications below the table, referring to the number of the individual task. In case you apply for instruments which are available where you work, but which are not at the project s disposal, please give detailed information. 14

15 Organizational Segment 1 Clinical project management 2 Project management 3 Data Management Institution/ Participant/ Trial Site No of items/ Kind of equipment/ Explanation Qualification of staff Salary group Total months Total ( ) 4 Biometry 5 Quality Assurance/ Monitoring number of visits per site mean number of days per visit monitoring costs per day total no of x each 6 Trial committees no. of DSMB members no. of x /p 7 Meetings/ Travel no. of attendees no. of x /p travel costs monitoring 8 Case payment assays/examinations per patient hours of staff per patient /patient x no of patients 9 Reference no. of samples@ x centers 10 Materials consumables trial manuals, files, forms 11 Trial drug /patient 12 Insurance /patient 13 Fees 15 Equipment 16 Other TOTAL months = staff indicated in months where applicable; = other expenditures indicated in Euro where applicable; /p = per person 15

16 11.3 Co-financing by industry and/or other third parties Co-financing by industry or other third parties is possible if the independence of investigators is ensured and terms and conditions of the financial commitment are disclosed. If co-financing is intended the application should briefly describe the type and volume of the intended co-financing, indicating the respective company or other third party. Describe the type and volume of support (including any services or consumables provided free of charge, e.g. drugs for the trial). Indicate the amount of support to be provided and assure in writing that the third party will render these services, stating their terms and conditions, if any. Assure that the coordinating investigator is independent, in particular with regard to the analysis of the trial and the publication of its results. A statement giving such assurances will be demanded by the BMBF after the review process is finished. Please don t make any agreements before notion of award has been made; please contact the funding organisation first! Appropriate agreements on intellectual property, confidentiality, publication of results, property rights should be concluded between all those playing a leading part in the conduct of the trial Other funding In case you have already submitted the same request for financial support or parts hereof to other institutions or the BMBF, please mention this here. Indicate those third parties which will provide funds, free services or consumables such as trial medication. If this is not the case please declare: "A request for funding this project has not been submitted to any other addressee. In case I submit such a request I will inform the Federal Ministry of Education and Research immediately". 16

17 E Mustervorlage für eine epidemiologische Studie Application for an Epidemiological Study Please prepare your application in English not exceeding 10 pages, including references. Signatures of principal investigator and responsible biostatistician/data manager are mandatory. Coordinator Title Condition/Topic Title, first and last name Institution Address Telephone and Fax address The medical condition being studied. Objective(s) Type of project Probands (key inclusion and exclusion criteria) Main outcomes to be analysed Statistical analysis Size and duration of Register/Cohort Summary Participating centers External cooperation partners Anonymisation or pseudonymisation of data and statistical details (max. 500 symbols including space characters) (optional, if applicable) 1 Background and previous work 1.1 Background Provide an overview about the background for the research question. Describe how the planned register/cohort is different from other existing or planned national or international registers/cohorts. 1.2 Own previous work Describe your previous work in the field and list all publications directly relevant for the planned project. 1.3 Medical problem Which medical problem is to be addressed? Which principal research questions/hypotheses are to be addressed? Bring them into order indicating major and minor motivations/starting hypotheses of the investigation planned. 1.4 Evidence Set your project into perspective. Give references to relevant publications and running comparable projects. What is the novel aspect that will be studied by the proposed project? 17

18 1.5 The need for the project What impact will the results have on clinical practice or understanding of the disease? Why is the project needed now? How will a) the individual patient and b) society/science benefit from the register/study? 2 Justification of design aspects 2.1 Type of project Is it a clinical/epidemiological register or cohort study? In case of an epidemiological register/cohort study: Is the project population-based? Which degree of completeness will be achieved? Which region will be covered? In case of a clinical register/ cohort study: Which institutions of the health care system will contribute to the project (number of private practices, regional and university hospitals, regions covered, completeness of patients recorded by the institutions)? Describe and justify the population to be studied (inclusion/exclusion criteria). Include reflections on generalisability and representativeness. What is the planned duration for the project? What are the long term plans for sustainability and how will the financing be assured? 2.2 Data items to be analysed Justify the data items chosen: Are there other projects that have utilized them before or guidelines proposing these data items? What is the planned follow-up for a single patient? Discuss the relevance of the data items for the target population. 2.3 Gender aspects Are gender specific aspects adequately addressed? Does the methodology ensure that possible sex- and gender differences will be investigated? Have possibly differential outcomes and impact of the research on women and men been considered? Are questionnaires, surveys etc. designed to unravel potentially relevant sex- and gender differences? Is there a gender balance in the project consortium and team? 2.4 Methods against Bias What measures against bias due to selection or confounding will be implemented? Which additional information will be documented for confounding? Please comment on anticipated non-response and missing data. 2.5 Data acquisition and storage How will the patients be elected and recruited for the project? How will the participating institutions be motivated for a timely and accurate data acquisition? Which instruments will be used to record the data? Are the instruments validated and reliable? Which standards will be used to classify diagnoses and stages of the diseases? Describe the concept of data acquisition and storage. How will the personal responsible for data acquisition be trained? Comment on the accessibility of data origins and on the possibilities to use or integrate already existing sources of data. 2.6 Biometric concept / Statistical analyses What is the proposed strategy of statistical analysis? Which data items and variables will be included in the analyses? What are the intended recruitment rate and total number of patients necessary for these analyses? Which concrete statistical evaluations are planned at what time and which methods will be used? What is the assumed rate of loss due to follow up or missing/incomplete data? On what evidence are these assumptions based? 18

19 2.7 Feasibility of recruitment What is the evidence that the intended recruitment rate and total number of patients for the project is achievable? Demonstrate conclusively the potential for recruiting the required number of suitable subjects (the best piece of evidence being pilot data collections and projects in a similar population/institution). 2.8 International collaborations If the proposed project includes non German centres or collaboration with organisations in other countries please give full details of funding arrangements agreed or under consideration. 3 ETHICAL CONSIDERATIONS Comment on ethical considerations relating to the project (confidentiality, informed patient consent). 4 PROJECT MANAGEMENT 4.1 Major participants # Name Affiliation Responsibility / Role Principal/Coordinating Investigator Responsible for Statistics Responsible for Quality Assurance/Data Management Please indicate roles of major participants 4.2 Project supporting facilities Which specific facilities and other resources are available for conducting the project? 4.3 Quality assurance Describe and justify the concept for quality assurance. How is the data integrity and plausibility controlled? Describe the actual organisational and technical measures for quality assurance and quality control (e.g. second control of data which cannot be controlled by plausibility tests, coding of data, second control of coding, documentation of data corrections). How and when will they be implemented? Are these e.g. outlined in a special quality manual ( Operationshandbuch )? Comment on the usefulness of feedback strategies concerning data quality. Which indicators are used to measure and quantify the quality of the register concerning e.g.: - structures (e.g. indicators measuring data plausibility) - processes (e.g. indicators measuring the organisation of data acquisition) - results (e.g. indicators measuring correctness, completeness, representativeness and accuracy). Comment on the necessity of an external quality assurance/monitoring. 4.4 Data safety concept How will the existing legal requirements for data safety be met? Describe the data safety concept applied and the planned data flow (diagram). If applicable, provide positive vote of the data security organisation in charge. Depending on the type of project, is anonymisation or 19

20 pseudonymisation of data planned? Comment on the following aspects of the data safety concept, if applicable: - Technical and organisational instruments - Central patients list (localisation) - Identification data - Pseudonymisation and depseudonymisation (localisation) - Informed patient consent - Patient right of access to personal data - Storage time of data - Workflow for quality assurance - Safety of data transmission and documentation - Policy document including all legal regulations and agreements 4.5 References Please list key references here (max. 5, font size not less than 6 pt). 4.6 Time flow / Milestones Please provide a proposal of milestones reflecting planning, recruitment status and data clearing/analysis progress. Include a diagram showing stages and milestones. Comment on the possibility of sustainable establishment of the project after funding, if applicable. 4.7 Financial details of the study Co-financing by industry and/or other third parties Co-financing by industry or other third parties is possible if the independence of investigators is ensured and terms and conditions of the financial commitment are disclosed. If co-financing is intended the application should briefly describe the type and volume of the intended co-financing, indicating the respective company or other third party. Details are to be specified: Describe the type and volume of support (including any services or consumables provided free of charge). Indicate the amount of support to be provided and assure in writing that the third party will render these services, stating their terms and conditions, if any. Assure that the coordinating investigator is independent, in particular with regard to the analysis of the project and the publication of its results. A statement giving such assurances will be demanded after the review process is finished. Reference is made to the legal provisions relevant to cooperation between industry, medical institutions and their staff Financial summary The overall expenditure should be summarized in the table below. Please, provide both personmonths and for employment costs and state the requested funds separately for each year of the project. 20

21 Seite Organizationa l Segment Scientific Management Organisationa l Management Data (Security) Management Statistical data analysis Quality assurance Meetings/ Travel 7 Case payment 8 Documentatio n payment Qualification and Task of staff/ Institution/ No. of items/ Participant/ Kind of equipment/ Trial Site Explanation 9 Materials Consumables 10 Equipment 11 Other No. of attendees ; No. of meetings ( / person) Assays/examinations per patient; hours of staff per patient; /patient x No. of patients documentation per subject/patient hours of staff per subject/patient / patient x No. of patients Salary group Total months TOTAL Total Budget: Institutional Overhead: e.g., Projektpauschale for Universities and University clinics; give amounts in Requested Budget (sum): Co-Financing applicable? Yes / No (e.g., by industry or other funding sources) m = staff indicated in months; = other expenditures indicated in Euro Total ( ) Justification