IWHOD 2014 docs combined - Copenhagen HIV Programme

COHERE Steering Committee Meeting Sala Levant 1, Sitges Thursday, 27 March 2014 10.00‐13.00 final Agenda item 4.1.1 4.1.2 4.2 7.5 12.2.1 12.2.2 Action Responsible Deadline Julia del Amo to take comments back to Juan Berenguer, revise the proposal (including the feasibility phase) and re‐submit to the CPH RCC for review by the EC and endorsement by the SC. Antonella to take the concerns back to Carlo, revise the proposal (including the feasibility phase) and resubmit to the CPH RCC for review by the EC and endorsement by the SC. Julia to revise the proposal based on the discussion; the proposal will then be sent to the CPH RCC for circulation to EC for review and SC for endorsement. Stéphane De Wit requested all SC representatives take time to consider these suggestions; the discussion will be raised again at a later date. RCCs to put together a calendar for abstract deadlines so authors are more aware of when they need to submit to EC and SC. RCCs to combine data specification sheet and project proposal Julia del Amo & Juan Berenguer 12 May, 2014 Antonella d’Arminio Monforte & Carlo Torti Julia Bohlius 12 May, 2014 All SC members 20 May, 2014 CPH & BDX RCCs 12 May, 2014 CPH RCC
01 April 2014
12 May, 2014 1. Welcome from Chair, Introduction of New EC Member, Apologies Stéphane De Wit welcomed the SC to the meeting and passed on apologies. He also welcomed Amanda Mocroft as the newest member of the Executive Committee. 2. Minutes for Approval The minutes from the SC meeting in Brussels were approved without comment. 3. Matters Arising 3.1 Changes to CPH RCC Management Dorthe Raben will gradually take over the role of CPH RCC lead from Jesper Grarup. Jesper Kjær has left CHIP and Rikke Brandt will replace him as CPH RCC DM, assisted by Dennis Kristensen. 3.2 New cohorts in COHERE The Swedish InfCare cohort with close to 10,000 patients, 6,000 of which are under active follow‐up, has expressed an interest in joining the COHERE collaboration and has, as the first step in the process, completed the cohort survey (circulated to the SC prior to the f2f meeting). We are currently in discussion with the cohort PI, Anders Sönnerberg, to clarify the cohort’s data transfer procedures and data quality. 3.3 Improving COHERE’s visibility (slides) 3.3.1 Debriefing of Stéphane’s presentation in Brussels. At the end of January, Stéphane gave a presentation on “Big European Collaboration” to a diverse audience in Brussels. COHERE contributed to this presentation by preparing a number of slides (enclosed) summarizing COHERE’s governance system and highlighting some of the key findings. The main take away message was that COHERE was less well‐known than some of the other cohort collaborations. Stéphane encouraged others to make similar presentations in their respective countries. It was suggested that a newsletter describing COHERE’s activities and achievements be circulated to each of the participating centers. Another suggestion was to improve the COHERE website so that it is more user‐friendly and modern. As all of the networks within EuroCoord could benefit from better online visibility, a discussion about how EuroCoord can raise the profile of all of the networks could be taken up by the WP3 group. As CHIP is in the process of redesigning its website including the COHERE page, the RCCs will capitalize on this opportunity to update and harmonize the COHERE website. 3.3.2 Panel Observation Research (EACS, 2015) In addition to the ideas above, it was suggested to hold a panel session at EACS showcasing European cohort HIV research. 4. New Proposals 4.1 Hepatitis Proposals (slides) 4.1.1 Trends in mortality according to HCV serostatus in patients infected with HIV in the era of cART in Western Europe, Julia del Amo Julia del Amo presented the proposal on behalf of the Project Lead, Juan Berenguer. This proposal was circulated to the EC late 2013 and has since been revised based on comments from the EC and the hepatitis group. The following points were made during the SC discussion: • The question was considered of scientific value and important • Concerns about quality of cause of death data and need to harmonize process with ART‐CC team from Bristol. There will also be overlap of data supplied to D:A:D. • In line with the challenges to have adequate data on causes of death, a number of issues were discussed such as the appropriateness of using multi‐imputation; it was suggested to look at cohorts which already collect cause of death data • It was recommended that a discussion be opened with DAD and ART‐CC re the ascertainment of causes of death so that potential areas of collaboration could be identified. • FHDH is looking at causes of death now and doesn’t have the data necessary nor do they feel multi‐imputation is the way to solve the problem with stratified variables. • The group had to be enlarged to include Maria Prins, given CASCADE had looked at a similar question in seroconverters a few years ago. Compared to those analyses, it was felt COHERE analysis would provide larger numbers, not only of seroconverters but also of seroprevalent subjects and more follow‐up than in the CASCADE analysis. • Julia suggested that they conduct a feasibility analysis and if the data quality isn’t good enough, the project could be dropped • Consider incidence of HCV analysis or sensitivity analysis on HCV RNA The issue of causes of death is important to all networks but it remains something that we struggle with. The experiences of ART‐CC and DAD have taught us that we communicate with each other too late. We can avoid these mistakes in the future by organizing a discussion between the three groups so we can look at causes of death in the same way. Heiner also raised the related point that data quality is equally important and should be focused on in the next application for funding. ACTION: Julia del Amo to take the comments back to Juan Berenguer, revise the proposal (including the feasibility phase) and re‐submit to the CPH RCC for review by the EC and endorsement by the SC. 4.1.2 Incidence and predictors of all‐cause deaths, liver‐related deaths and AIDS‐related deaths in a large cohort of HIV/HCV ‐infected patients with liver cirrhosis, Carlo Torti Antonella d’Arminio Monforte presented on behalf of Carlo Torti. This proposal was circulated to the EC late 2013 and has since been revised based on comments from the EC and the hepatitis group. The following points were made during the discussion: • Limitation in the number of patients with HCV RNA sensitivity • This is a natural history study, so it would be interesting to see to what extent treatment affects the outcome • If the focus is only on patients who are on treatment, there may be a bias towards only the sickest patients. A suggestion was made to include patients who have received prior treatment and haven’t failed. • Suggestion to do a sensitivity analysis to ensure the data is representative of all patients. Needs a more extensive feasibility phase, showing that we don’t know what’s available in the database. ACTION: Antonella to report questions raised back to Carlo, revise the proposal (including the feasibility phase) and resubmit to the CPH RCC for review by the EC and endorsement by the SC. 4.2 Malignancy Proposal (slides) Incidence and risk factors for developing Kaposi Sarcoma in the era of combined antiretroviral therapy in Europe, Julia Bohlius Julia presented the Kaposi Sarcoma in Europe proposal, which has evolved from the previously approved project ‘Incidence and prognosis of AIDS‐defining cancers in the era of cART: Southern Africa, Europe and North America compared’. An abstract based on this new proposal was submitted to CROI 2014 and accepted as a poster presentation. Julia reported that two key risk factors, MSM and patients of African origin, are not being looked at in COHERE or other networks. After analyzing the data available, only ATHENA and FHDH could possibly have sufficient cases of KS incidence for an individual cohort analysis, and for African origin, only FHDH. The following points were made during the discussion: • The proposal contains 6 objectives, some of which do not have a clear need for COHERE’s power. Each objective needs to maintain the principles of COHERE. • Objective #4, to identify short and long term risks of developing KS and changing risk factors over time in patients on cART, is similar to what FHDH published on, although they did not look at changing risk factors over time. • Concern that individual cohorts could look at incidence rate on their own. Julia Bohlius pointed out that it is not the number of cases available that is the problem in a single cohort analysis, but rather, the objectives could be done by individual cohorts but that incidence rate calculation was not standardized, so bigger numbers are needed. The difference between this project and the larger IeDEA collaboration from which this evolved, is that that the purpose of the IeDEA project is to look at large geographic differences, will be more heterogeneous, and will not have a very in depth analysis. • Suggestion to only focus on the objectives which clearly need COHERE power, for example, other studies look at incidence but not country of origin, which is where COHERE data could be interesting. • A statistical plan should be included in the project proposal under Analysis. This would facilitate the publication process as more journals are requesting protocols to document analyses. During the development of a project, which could lead to new questions, it is very important that each question be discussed first with the group and then presented to the EC/SC to evaluate whether it still fits COHERE’s principles, and identify potential overlaps with other collaborations. ACTION: Julia Bohlius to revise the proposal based on the discussion, namely: • Focusing on objectives 3 and 4 • Clear justification for using COHERE as part of the Feasibility section of the proposal • Statistical plan included under Analysis section of the proposal The proposal will then be sent to the CPH RCC for circulation to EC for review and SC for endorsement. •
5. Discussion 6. Collaboration with ART‐CC (slides) Jonathan Sterne presented on behalf of ART‐CC. A main focus of ART‐CC is cause‐specific mortality but COHERE cohorts do not have a standard method for collection cause of death, making it difficult to match with ART‐CC’s data, which is collected using an adaptation of the CoDe algorithm. It was suggested that this become a priority for ART‐CC and COHERE to standardize the collection in order to avoid the reoccurring discussion on how to collect cause of death. The current MRC grant ends in January, 2015. The next steps for ART‐CC and their proposed themes for the 2014 grant application (analysis 2015‐2018) will be to focus on implications for ART treatment strategies for clinical events and cause‐specific mortality, ageing and multi‐morbidity, prognosis in the era of HCV treatment, and prognosis comparisons across regions. In addition to the MRC grant, the next steps for ART‐CC include addressing potential overlaps with cohorts and other collaborations, assessing data availability, and coordinating regional collaborations. It was noted that there is clearly a need for a workshop on cause of death as well as further discussion on how to highlight the COHERE/ART‐CC collaboration to other collaborations, especially in North America. 7. Data Management (slides) 7.1 Update since SC F2F, Brussels 7.1.1 SOP process & projects included 7.2 Status of 2014 Merger Monique and Rikke presented an update on the 2014 data merger. The data submission deadline is 30 April 2014. Four cohorts have not yet submitted data. The question was raised about what to do when cohorts do not contribute data on time and Monique and Rikke suggested to either use their data from the last merger, which may mean new projects would not receive data from them, or leave them out of the merger completely. It was decided that if cohorts do not submit data by the deadline, DMs would ask whether they were interested in having their 2013 submission in the 2014 merger. This was well received by the SC; however, it would need to be noted in the methods’ section of any related publications/presentations that some data is from 2013 and some from 2014. If data is not submitted for 2 consecutive mergers, the standard COHERE policy of exclusion from the collaboration will apply. 7.3 Update from 2013 Merger 7.3.1 HCC Project: RedCAP & e CRF Rikke presented the HCC e‐CRF, which is a standard RedCAP survey. This tool will be used by COHERE for future ad‐hoc questionnaires/surveys. 7.3.2 Coding Errors As noted at the SC meeting in Brussels in 2013, some cohorts did not use the most recent coding convention for the 2013 merger. Jesper Kjær drafted an impact report which was circulated to the EC. New extractions were provided to all of the cohorts. 7.4 New HIV‐DDM features In order to avoid future coding errors, a quality assurance check has been added to the HIV‐DDM tool so data managers can verify they are using the most updated codes. To improve transparency, cohorts will now be able to see immediately how many patients per project their data includes. COHERE DMs hope that this will serve to catch some of the more obvious coding errors. 7.5 Pros and Cons of annual mergers Prior to the SC meeting, Niels Obel suggested conducting the data merger every two years, for example, rather than annually. The suggestion is based on the concern that errors in the data are caught rather late in the project development. Conducting the data merger less frequently would enable project leads and data managers ample time to find errors in their data and address these errors before the next data merger starts. As the schedule is now, cohorts may have already submitted data for a current merger before learning that there is an error in their previous data submission, thus not allowing them time to correct the error. There may also be a financial benefit in conducting the mergers every second year. However, a concern about less frequent mergers would be the increased delay from the time a project is proposed to the time it receives a data set. It was suggested that older versions of data sets could be released so programs can be written and then replaced by new data when it becomes available. It was also noted that each cohort PI needs to do review the distribution of their data to catch the more obvious mistakes, such as country of origin. Niels also proposed that the SC meet for a one‐day meeting in conjunction with a conference, rather than the 2 to 3 hour face‐to‐face meetings we have now. ACTION: Stéphane De Wit requested all SC representatives take time to consider these suggestions; the discussion will be raised again at a later date. 8. Discussion 9. EuroCoord Updates 9.1 Governance ‐Annual rotation of the EuroCoord Council of Partner (CoP) Chair: Dominique Costagliola has taken over as the new CoP Chair for 2014 replacing Jose Gatell. – Executive Board: COHERE will take over chairmanship from EuroSIDA (Ole Kirk), as next chair, starting in Sept 2014. 9.2 WP updates and EuroCoord recent activities Beginning 2014: preparation of the 3rd periodic report, submitted to the European Commission early March. Comments and queries from the European Commission expected in April. – WP2 on training and outreach: – WP4 – Data Management and an important contribution from COHERE. o An update of the inventory survey was done in February 2014. o HICDEP_1.7 was released in Fall 2013: discussions are ongoing on format of socio‐
economic‐, Hepatitis‐, and on cancer/malignancies variables in collaboration with IeDEA o IeDEA collaboration: A joint luncheon meeting around data harmonization will be held at IWHOD on Friday 28 March abstract with IeDEA and EuroCoord o Monique Termote will give a short talk on behalf of the WP4 on “Status of data harmonization: challenges, opportunities and future harmonization of data exchange between cohorts.” – EuroCoord presentations at 18th IWHOD. Orals: 1 COHERE, 1 COHERE and ACHIEV2E collaboration, 1 EuroSIDA, 1 SSOPHIE Project group (WP15‐Modelling); Posters: 3 CASCADE, 1 COHERE, 1 ECS, 1 COHERE, NA‐ACCORS and CNICS collaboration 9.3 EuroCoord Scientific Retreat and H2020 –
H2020: Consultation was conducted in Dec 2013‐Jan2014 to generate ideas on how to renew ourselves. Next steps were discussed at the EuroCoord Scientific Retreat, 26 March 2014 in Sitges. HIV cohorts are not part of the next call, but may be in 2016 and thereafter so the networks have started a proactive search for other funding sources. At the scientific retreat, the group reviewed and discussed new and original science to add to the EuroCoord agenda and present to the European Commission. The EuroCoord scientific retreat agenda was organized around the following themes that came up from the H2020 consultation: Demographic change and HIV in Europe; Social determinants including inequalities in health systems and their impact on HIV across Europe; Multi‐morbidity in HIV (including Hepatitis B and C); Biomarkers for prognostic and diagnostic use in HIV; Controlling the epidemic – screening, prevention and treatment and their impacts on the epidemic. There was an extensive discussion on engaging with social and behavioral scientists, health economists, etc., in order to bring new scientific expertise in to the EuroCoord collaboration and explore new ways of collecting and analyzing data. 9.4 Ethics Agreement In accordance with The European Commission request that the EuroCoord Network obtain and compile ethics approvals from all EuroCoord partner affiliated cohorts, it was decided by the EuroCoord Executive Board that this be done via the COHERE Regional Coordinating Centers (RCCs) in Bordeaux and Copenhagen. In November, 2013, RCCs requested that cohorts submit scanned copies of these documents to the supportive RCC. For those cohorts located in countries where national legislation does not oblige ethical clearance to conduct observational, non‐intervention studies and for those cohorts that were formed before the legislation requiring investigators to obtain ethical clearance took effect (nor was it applied retroactively), cohort PIs signed a waiver attesting to the circumstances that exempt their cohort from obtaining ethical clearance. Thanks to everybody’s efforts, this process was successfully completed for all EuroCoord partner affiliated cohorts. However, some further information may be required and the process for compiling this information was discussed within the EuroCoord Executive Board. UCL will now be leading the process and will be contacting the cohorts as needed for additional information. 10. Ongoing Scientific Projects (project update spreadsheet) 10.1 Prognosis and Effect of ART (slides) Jonathan Sterne presented the update for the prognosis theme. The PLATO‐II Incidence of TCVF project will not be pursued any more. 10.2 Opportunistic Infections Hansjakob Furrer presented the OI update and reported that José Miro is working on a project that focuses on patients with risk for negative outcomes. The group needs a quite detailed description of the end of clinical outcome and expressed that if they wanted to exploit data from the entire COHERE network. They need to find way to get information on rare cases. The OI group was given an older dataset to train the new statistician and prepare the scripts for analyses on the 2014 merger as these must be completed soon after the extraction of datasets for 2014 merger projects. 10.3 Hepatitis (slides) The e‐CRF for the HCC project has been distributed to those cohorts who had HCC data in the 2013 merger. The deadline for collection is summer 2014 so that analysis can be completed in time to submit to CROI 2015. It was noted that the RedCAP survey is a good tool, however, it still takes about 3 hours for each case to be entered, as many are in archived patient journals. Antonella and Francois confirmed that the task of collecting HCC data was time‐consuming, despite hope that most journals had been digitalized, which is why cohorts are reimbursed for their efforts. 10.4 Malignancy (slides) Julia Bohlius presented the malignancy update. The incidence of Kaposi sarcoma in Europe was accepted as a poster and selected for a Themed Discussion at CROI 2014. The proposal has been revised and was presented to the SC at this meeting for endorsement (see item 4.2 above). Heiner presented the ‘Association of chronic HBV and HCV co‐infection with the development of NHL in HIV‐infected patients’ project. The dataset was cleaned and the analysis plan drafted in March 2014 and the group expects the project to be finalized September 2014. A discussion arose about selection bias, which will be continued within the project working group. 10.5 Late Presenters Amanda Mocroft presented a brief update on the Late Presenters project. A preliminary analysis was discussed within the working group after looking at 2013 data. Once the 2014 data is available, the group can confirm their preliminary findings, after which they plan to submit an abstract to the HIV in Europe conference in October 2014. 10.6 Migrants and Socioeconomic Inequalities Migrants – An extraction from the 2013 merger was received in Jan 2014 and updated analyses including data from FHDH and PISCIS are ongoing. Work on cause‐specific mortality harmonization for these analyses is being done, in collaboration with ART‐CC team. Economic inequality ‐ The first paper was submitted to BMJ and discussion around the second paper based on the EACS presentation will start soon. 11. Discussion 12. Governance (slides) 12.1 Changes to COHERE MOP & Appendices The Manual of Operations and Appendices, previously endorsed in October 2013, were updated to reflect the changes in COHERE governing bodies, policy on authorship and the admission of new cohorts. The updates included a revised Project Proposal template. This will be made available on the COHERE website. Given the regular changes to the MOP and Appendices, PLs should refer to the most recent version. 12.1.1 Authorship The COHERE Authorship group was established in January 2014 and met to discuss and suggest reforms for the COHERE authorship policy. The policy has been revised to allow for more flexibility for manuscripts, abstracts, including collaborations. 12.2 Project Lifecycle Jesper Grarup presented slides on the lifecycle of a COHERE project. Theme and Project Leads, as well as any member of the SC contemplating submitting a new project proposal, were encouraged to review the process and familiarize themselves with their respective roles. Clarification was made about establishing the project group, which is the responsibility of the Project Lead, with support from the RCCs. Going forward (2014 merger projects), the project group would be established within 3 months of receiving the dataset with the assistance of the RCCs. This way it would reflect the breakdown of data contributed. The RCCs ask for project group nominations when projects are endorsed by the SC and these names are then sent on to the Project Lead. The project group lists are centrally managed at the RCCs and RCCs should always be made aware of any changes to the groups. 12.2.1 Circulation deadlines As shown on the project lifecycle presentation, Project Leads must circulate manuscripts and abstracts to the Theme Group, EC and SC with sufficient time for each group to review and/or endorse. Project Leads were encouraged to be aware of submission deadlines for review and endorsement by the SC and EC. It was noted that flexibility with endorsement timelines is needed for some cohort PIs, who need to go back to their own Steering Committees for project endorsements. ACTION: RCCs to put together a calendar for abstract deadlines so authors are more aware of when they need to submit to EC and SC. 12.2.2 Proposal process In addition to the information in the project lifecycle presentation, SC representatives were also reminded that a data specification sheet needs to be submitted together with the project proposal. ACTION: RCCs to combine data specification sheet and project proposal 13. Communication/Dissemination 13.1 Manuscripts and presentations Conferences CROI 2014: The abstract “Kaposi Sarcoma in the era of combination anti‐retroviral therapy”, submitted by Natascha Wyss, Matthias Egger, Julia Bohlius on behalf of the Malignancy Working Group for COHERE in EuroCoord, was accepted as a poster presentation as well as for a Themed Discussion on Kaposi Sarcoma at the 2014 Conference on Retroviruses and Opportunistic Infections. IWHOD 2014: Three abstracts were submitted to IWHOD 2014. The abstract, “Risk of Aids, death and control loss in HIV controllers in COHERE”, submitted by Laurence Meyer and Olivier Lambotte, was accepted as an oral presentation. As was the abstract, entitled “CD4 cell count dynamics in HIV‐1 and HIV‐2 seroprevalent patients while naïve for antiretroviral treatment – a multicohort study”, submitted by Linda Wittkop and Sophie Matheron on behalf of the COHERE in EuroCoord and ACHIEV2E study team. Finally the abstract, "Starting cART in antiretroviral‐naïve HIV‐1–infected patients presenting with cryptococcal meningitis, presented by Sue Ingle, José Miro, Hansjakob Furrer, Amy Justice, Mike Saag, Christian Manzardo, Anna Esteve, Jonathan Sterne, Margret May on behalf of COHERE, CNICS and NA:ACCORD, was accepted as a poster presentation. International Resistance Meeting 2014: An abstract entitled, "Improving the Interpretation of HIV‐1 Genotypic Resistance to Darunavir by Treatment Outcomes: Derivation of a Weighted Score and its Application to Different Viral Subtypes", was prepared by Andrea De Luca, Philippe Flandre and Diane Descamps in collaboration with the working group and submitted on the 24 March, 2014. Manuscripts: As announced in the January, 2014 newsletter, two manuscripts have been published since the last meeting of the COHERE SC. “Long‐term mortality in HIV positive individuals virally suppressed for more than three years with incomplete CD4 recovery”, a project in collaboration with ART‐CC, was accepted at CID. Furthermore, Dr. Frederik Neess Engsig, the lead author, was interviewed by Infectious Disease News, a monthly publication for ID specialists in the United States, about the main findings. A summary of findings for the patient community has been prepared and forwarded to the EuroCoord Secretariat. “Factors associated with short‐term changes in HIV viral load and CD4 cell count in antiretroviral‐naïve individuals”, led by Fumiyo Nakagawa and Andrew Phillip, has also been accepted at AIDS as a Brief Report. A summary of findings for the patient community has been prepared and forwarded to the EuroCoord Secretariat. CD4 Cell Count Dynamics in HIV‐1 and HIV‐2 Infected Patients – A Multinational Multicohort Study, led by Linda Wittkop and Sophie Matheron on behalf of the COHERE in EuroCoord and ACHIeV2e Project Group, was submitted to a special addition of JAMA in early February, 2014. Delayed diagnosis of HIV infection and initiation of antiretroviral therapy in a large European collaboration: inequalities by level of education, led by Sara Lodi and Julia del Amo is in the process of being submitted to the British Medical Journal. The PLATO II group reduced the word count of their manuscript, “Frequency of identification of triple class drug resistance associated mutations in patients experiencing virologic failure to the three original antiretroviral drugs classes”, to 2000 words with the intention of submitting it to JAIDS as a brief report. 14. Discussion 15. AOB The topic of how we can improve the quality of data within COHERE was raised, especially in regards to causes of death data and investing in tasks like the HCC project, where cohorts are asked to go back to potentially archived patient records. This should be an ongoing discussion within the network. We should look for tools to improve data quality, in particular on causes of death. Next SC Meeting: Glasgow, Monday, 03 November 2014, 16.30 – 19.15 COHERE Steering Committee Meeting
Sala Levant 1, Sitges
Thursday, 27 March 2014
10.00-13.00
Attendees
Name
Cohort
Murielle Mary-Krause
FHDH
Ferdinand Wit
ATHENA
Dominique Costagliola
FHDH/EC
Stine Jakobsen
CPH RCC
Ole Kirk
EuroSIDA
Linda Wittkop
BDX RCC
Jonathan Sterne
ART-CC
Hansjakob Furrer
SHCS
Diana Barger
BDX RCC
Maria Campbell
CPH RCC
Monique Termote
BDX RCC
Christine Schwimmer
BDX RCC
Stéphane De Wit
COHERE EC Chair/St. Pierre
Rikke Salbøl Brandt
CPH RCC
Dennis Kristensen
CPH RCC
Robert Zangerle
AHIVCOS
Geneviève Chêne
BDX RCC
Jesper Grarup
CPH RCC
Name
Cohort
Jose Miro
PISCIS
Laurence Meyer
SEROCO
Heiner Bucher
CASCADE
Niels Obel
Danish HIV
Julia Bohlius
SHCS
Matthias Egger
SHCS
Julia del Amo
Co-RIS/EC
Antonella d’Arminio Monforte
ICONA/EC
Jordi Casabona
PISCIS/EC
Manuel Battegay
MoCHIV/EC
Amanda Mocroft
EuroSIDA/EC
Vicenzo Spagnuolo
HSR
Ramón Tiera
VACH
Agenda
IM IT AMACS ECS-M o t he rs & ECS -Inf an ts NS HPC-Mo t he rs & NHP S-I n fan ts PI SCI S
KO M P NET C ASC ADE A NR S CO 2 SEROCO F r a nk fu r t HIV Co ho rt S t ud y S a n Ra ff ae le
ANRS CO1/CO10 EPF UK CHIC Athena ITLR-Mothers & ITLR-Infants Swiss HIV Cohort Study
1. What happened since last SC meeting
ICC ANRS CO6 PRIMO Co-RIS MOCHIV-Mothers & MoCHIV-Infants The Italian MASTER Cohort
CHIPS ANRS CO4 French Hospital’s Database on HIV HIV-MIP-Mothers & HIV-MIP-Infants
• SOP process and projects included
GEM ES-Hae mo A NR S CO 3 AQ UI TAINE E u roSI DA M ad ri d Coho r t HI V Chil d re n VACH
M o d e n a C o h o r t S t u d y D a n i s h H I V S t u d y A NR S CO 8 C O PI LO T E I CON A S t . P i e r r e
Collaboration of Observational HIV Epidemiological Research Europe
• Changes to the merger process
Coordination: Copenhagen HIV Programme (CHIP) & Institut de Santé Publique,d'Epidémiologie et de Développement (ISPED)
2. Current merger status
COHERE
3. Update Merger 2013
• Hepatocellular carcinoma project: RedCAP and eCRF
• Coding errors
Data management
4. New features in HIV Distributed Data Management (HIV-DDM)
• R-pdf output
• Number of patients per projects
5. Looking to the future: frequency of COHERE mergers
SC meeting, 27 April 2014
1
2
SOP process
November 2013
• TCs per theme with theme leads /project leads were done in November
2013
– Project data specification forms were reviewed on inclusion criteria and tables
and variables needed.
Projects included
•
Project C1 - Antiretroviral Therapy Cohort
Collaboration (ART-CC)
–
•
•
TCs with cohort data managers for a debriefing of the previous merger and
discuss plans and timelines for the new merger
Project were formulated into a joint SOP and the SOP was send for
approval to the theme and project leads and the EC.
– 3 newly added
‒ 1 table renamed
• Added/changed 14 variables
– 12 newly added
– 2 redefined
• Additional codes has been introduced for 12
variables
 Causing additional workload on the cohorts
Project OI3 - Role of current HIV RNA as a CD4
independent risk factor for TB incidence in HIVinfected persons
•
Project EU3 - Treatment Change Database
•
Project P1 - Immunodeficiency at the start of ART
in adults: A global view
•
–
–
Project lead: Kholoud Porter
Project leads: Laurence Meyer, Olivier Lambotte
–
Project leads: Casper
‒ Project leads: Matthias Egger, Ole Kirk
•
•
– Revisions February 17th and March 20th
• Added/changed 4 new tables
•
•
–
Project P2 - Immunodeficiency at the start of ART
in adults: A global view
‒ Project leads: Matthias Egger, Ali Judd, Mary-Ann Davies
•
Project P3 - When to start ART in children aged 25 years of age: a causal modelling study
‒
Changes to the SOP
Project OI2 - Evaluation of guidelines for
prophylaxis of opportunistic infections in the era
of cART - toxoplasmosis
Project EU1 - Late Presenter
– Project lead: Ole Kirk
Project EU2 - HIV-Controller
January 2014:
• TC with cohort data managers to discuss the SOP, timelines and submission
options
•
Project C2 - CASCADE
•
•
• SOP was circulated to the cohort data managers in January, put into force
in February 1st
Project OI1 - Evaluation of guidelines for
prophylaxis of opportunistic infections in the era
of cART - Pneumocystis, CMV, MAC,
Cryptococcosis
•
–
December 2013:
•
Project leads: Jonathan Sterne, Margaret May and Sue Ingle
Project lead:s: Mary-Anne Davies and Matthias Egger
Project M1 - Incidence and Prognosis of AIDSdefining cancers in the era of cART: Southern
Africa, Europe and North America compared
–
•
Project leads: Julia Bohlius, Matthias Egger
Project H1 - Optimal treatment strategy for
HCV/HIV co-infected individuals
–
–
Project leads: Jose M. Miro, Hansjakob Furrer
Project lead: Hansjakob Furrer
Project OI4 - Role of current HIV RNA as a CD4
independent risk factor for TB incidence in HIVinfected persons
–
Project lead: Hansjakob Furrer
Project OI5 - History of tuberculosis as a risk
factor for developing opportunistic diseases after
starting antiretroviral treatment in HIV-infected
patients
–
•
Project leads: Hansjakob Furrer, Jose M. Miro
Project lead: Hansjakob Furrer
Project OI6 - Optimal timing for starting cART in
antiretroviral-naïve HIV-1–infected patients
presenting with central nervous system (CNS)
toxoplasmosis
–
Project lead: Hansjakob Furrer
Project leads: Giota Touloumi
2013 merger – lessons learned
We have identified three areas we need to improve on/be more firm
about to avoid the delay we experienced with the finalisation of this
years merger:
1.For the timeliness of the SOP we need to have projects to be included
approved and data requirements defined in due time already this year.
2.We need to help data managers to better understand the inclusion criteria to
the individual projects so that they can validate that their data coding/mapping
into HICDEP is correct.
The HIV-DDM tool will be expanded to generate a stats report on the
submission and the selected projects.
Changes to the merger process
Last year’s promises
3.We need to be more strict about the deadlines specified in the SOP – this
means that cohorts not adhering to the deadlines could ultimately cause the
cohorts data not to be included in the final merger. This will up to the EC and
SC to decide in case a similar situation should occur in 2014.
1
Current merger status
Final deadline 30th of April!
2013 merger – lessons learned
We have identified three areas we need to improve on/be more firm
about to avoid the delay we experienced with the finalisation of this
years merger:
Bordeaux
1.For the timeliness of the SOP we need to have projects to be included
approved and data requirements defined in due time already this year.
2.We need to help data managers to better understand the inclusion criteria to
the individual projects so that they can validate that their data coding/mapping
into HICDEP is correct.
The HIV-DDM tool will be expanded to generate a stats report on the
submission and the selected projects.
3.We need to be more strict about the deadlines specified in the SOP – this
means that cohorts not adhering to the deadlines could ultimately cause the
cohorts data not to be included in the final merger. This will up to the EC and
SC to decide in case a similar situation should occur in 2014.
Copenhagen
• 15 expected:
– 13 cohorts have
done initial data
submission
– 1 cohort has not
done an initial data
submission
– 1 cohort will not
submit data
• 21 expected:
– 19 cohorts have
done initial data
submission
– 2 cohorts have not
done an initial data
submission
Next steps
Not meeting the deadlines, what
now?
For the cohorts not be able to submit for the 2014
COHERE merger within the defined timelines, we could
use their data submissions of last year and merge these
with the 2014 data.
Pros:
Data of the cohort is included in the COHERE merger.
Cons:
The cohorts having submitted the data with the tool last
year, did submit on project level, new projects might not
match with the eligibility criteria of last year’s projects.
Next steps
Deadline
Action
Responsible Documents
30 April
Final submission of data
Cohort data
manager
10 May
Final RCC database
RCC
Final dataset
16 May
QA report
RCC
Report
30 May
Duplicate identification
RCC
Overlap table
30 May
Resistance Data Alignment Protocol
RCC
Resistance dataset
6 June
Data anonymisation
RCC
6 June
Descriptive statistic reprot
RCC
14 June
Delivery of datasets to project leads
Report
Project datasets
Hepatocellular carcinoma
project: RedCAP and eCRF
FINAL SUBMISSION OF DATA
DUPLICATE IDENTIFICATION &
RESISTANCE DATA ALIGNMENT
PROCES
DELIVERY OF DATASETS TO
PROJECT LEADS
FINAL RCC DATABASE
30 Apr
15 May
30 May
14 Jun
QA REPORT
DATA ANONYMISATION AND
STATISTICAL REPORT
https://www.chip-crf.info/redcap
2
RedCAP
RedCAP
https://www.chip-crf.info/redcap
https://www.chip-crf.info/redcap
Code
Coding errors.
Overlapping codes
the Origin example
eCRF
Code
10
11
12
20
30
40
50
51
52
60
70
71
72
99
Region of origin (HICDEP 1.5)
http://hicdep.org/wiki/Hicdep_1.50/
TableBas/FieldOrigin#CodingTable
Africa
Northern Africa
Sub-Saharan Africa
Asia
Oceania (not Australia)
Australia & New Zealand
Americas
North America
Central & South America
Middle East
Europe
Western Europe
Eastern Europe
Unknown
https://www.chip-crf.info/redcap
Code
Coding errors.
Overlapping codes
the Origin example
Code
10
11
12
20
30
40
50
51
52
60
70
71
72
99
Region of origin (HICDEP 1.5)
http://hicdep.org/wiki/Hicdep_1.50/
TableBas/FieldOrigin#CodingTable
Africa
Northern Africa
Sub-Saharan Africa
Asia
Oceania (not Australia)
Australia & New Zealand
Americas
North America
Central & South America
Middle East
Europe
Western Europe
Eastern Europe
Unknown
Code
010
011
012
020
030
040
050
051
052
060
070
071
072
099
UN Region codes
http://unstats.un.org/unsd/
methods/m49/m49regin.htm
‐‐‐‐
Western Africa
Algeria
Andorra Eastern Asia
Austria
Bangladesh
Armenia
Barbados
Bermuda
Bosnia and Herzegovina
‐‐‐‐
Botswana
‐‐‐‐
Region (HICDEP 1.6)
http://hicdep.org/wiki/Hicdep_1.60/TableBas/
FieldOrigin#CodingTable
001
World
002
Africa
014
- Eastern Africa
017
- Middle Africa
015
- Northern Africa
018
- Southern Africa
011
- Western Africa
019
Americas
419
- Latin America and the Caribbean
029
- - Caribbean
013
- - Central America
005
- - South America
021
- Northern America
142
Asia
143
- Central Asia
030
- Eastern Asia
034
- Southern Asia
035
- South-Eastern Asia
145
- Western Asia
150
Europe
151
- Eastern Europe
154
- Northern Europe
039
- Southern Europe
155
009
Region (HICDEP 1.6)
http://hicdep.org/wiki/Hicdep_1.60/TableBas/
FieldOrigin#CodingTable
001
World
002
Africa
014
- Eastern Africa
017
- Middle Africa
015
- Northern Africa
018
- Southern Africa
011
- Western Africa
019
Americas
419
- Latin America and the Caribbean
029
- - Caribbean
013
- - Central America
005
- - South America
021
- Northern America
142
Asia
143
- Central Asia
030
- Eastern Asia
034
- Southern Asia
035
- South-Eastern Asia
145
- Western Asia
150
Europe
151
- Eastern Europe
154
- Northern Europe
039
- Southern Europe
155
- Western Europe
009
Oceania
053
- Australia and New Zealand
054
- Melanesia
057
- Micronesia
061
- Polynesia
The Cause of death example
from 2013 Project A
Background
• Distribution of codes used to code causes
of death in tblLTFU indicated that the old
2011 coding rather than the 2013 CoDe
coding had been used by two cohorts.
- Western Europe
Oceania
053
- Australia and New Zealand
054
- Melanesia
057
- Micronesia
061
- Polynesia
3
The Cause of death example
HIV-DDM tool – QA check to
verify the codings
Resolution
• The merger process been expanded to
include both QA checks that require
cohorts to sign off on the distribution of the
used codes, both in the QA checks but also
in a descriptive stats report visualising the
distribution.
HIV-DDM tool - R-output pdf
www.hiv-ddm.net
HIV-DDM tool - R-output pdf
www.hiv-ddm.net
HIV-DDM tool - R-output pdf
www.hiv-ddm.net
4
www.hiv-ddm.net
www.hiv-ddm.net
www.hiv-ddm.net
HIV-DDM tool
Number of patients per projects
www.hiv-ddm.net
5
Merger every other year?
Pros
Cons
• Sufficient time to
• Too long time from
correct coding and/
proposal to receipt
or data errors and
of dataset
implement central
• Quality of submitted
coding (e.g. death)
data is more
 improve quality
dependent on DM
• Less resource and
skills than the
funding needed
cohort databases
Improved networking, better
science?
• The SC meeting agenda is always packed
• Why not replace one of the SC meetings
with a whole day meeting?
– Discuss projects more in detail
– Generate new ideas
– Establish networks
– E.g. prior to EASC and Glasgow
conferences?
6
10/9/2014
Proposal form, incl. budget if new data
Project Lifecycle
Chair
Project Lead and/or team
Theme Lead & Theme Group Overlap check (2 weeks)
RCCs
EC (1 week review)
SC (2 week review)
RCCs
COHERE Governance
Abstract/oral
(1 week before submission/
presentation)
COHERE Steering Committee Meeting
Sitges, 2014
Approved Project
Analysis report
Project Lead establish project team (all cohorts)
Project Lead establishes writing group (contributing cohorts)
Manuscript (3 weeks before submission)
RCCs
Abstract (revise & submit
Manuscript (revision review 1 week before submission)
EC/SC Changes to the MOP & Appendices
• Previous endorsement of MOP: October 2013 (Manual of Operations and Appendices, version 3)
• Proposal Template Now Includes • Proposal process steps and timelines
• Potential conference abstracts & manuscripts
• Feasibility phase
• Authorship
• Rules apply to manuscripts & conference abstracts
– All COHERE projects, including collaborations
• Exceptions on case‐by‐case basis
–
–
–
–
Requests submitted to RCC
Justification required for consideration
Approval from EC/SC
As early in the process as possible
1
10/9/2014
Background
Improving COHERE’s visibility
2014-15
• Stéphane De Wit’s Presentation on «Big
Cohort Collaborations» (Jan 2014, Brussels)
– Well received, sparked interest BUT COHERE
is less well-known than many of the other
cohort collaborations
– Given the current funding environment,
improving COHERE’s visibility was raised as a
key issue by Stéphane De Wit
• Strategies for improving COHERE’s visibility
were discussed with the EC (Feb 2014)
Brainstorming
1. EC/SC members hold presentations
highlighting COHERE’s and EuroCoord’s
work in respective countries
– Presentation has been organized in France at
AC5 in Summer, 2014
2. COHERE to organize a panel
presentation at the next EACS 2015,
underscoring the importance of
observational research
– In collaboration with EuroCoord? Others?
Past Sessions / Talks
March, 2011: Oral, C.Sabin,
EuroCoord at the EACS in
Belgrade (2011)
July, 2012: Joint symposium
with NA-ACCORD at
Washington Conference AIDS
on role of cohort collaborations
in HIV research
August, 2013: EuroCoord WP4
and IeDEA Panel at MedInfo
International Journal of
Epidemiology COHERE
Cohort Profile
Aim : To allow others to learn from the
experience of large, complex cohort
collaborations like COHERE
- Brings visibility to the collaboration
- Can be cited in the methodology sections of COHERE
publications
- IJE allows cohorts to make updates to their profile each
year
Discussion and next steps…
Manuscript is well underway
– Meeting with the working group in Sitges
1
10/9/2014
COHEREHepatitisGroup– March,2014
2)Hepatitisprojectsstartedin2014
1)Completedandongoingprojectsandanalyses
• HCVtreatmentwithINF,CD4andmorbidity/mortality
CSmit,publishedonAntivTher,2012
• ResponsetoINF‐alphaandribavirinandall‐causemortality
ACozzi‐ Leprietal.EACS2013
P.Larsetal.Manuscriptinpreparation
• EffectofNRTIandpegylatedinterferononthecourseof
hepatitisC
CSmit,Analysisinprogress
3)Projectplannedforthe2015merger
• ScreeningpracticesforHCVcomplications
MarcvanderValk
afterfeasibilitywasexploredinlate2013
• Hepatocellularcarcinoma(HCC)inHIV‐infectedpatients
• Cases of HCC occurring in HIV-infected patients identified on
the basis of the 2013 COHERE merger
• A web form was set up, tested and circulated
• Extra data for each HCC case is now asked to cohorts
• Data collection with RedCap®
• Dead-line for collecting forms: one year
• Nominal fee per form completed
4) Projects to be approved (Concept sheet)
• Incidenceandpredictorsofall‐causedeaths,liver‐related
deathsandAIDS‐relateddeathsinalargecohortof
HIV/HCV‐infectedpatientswithlivercirrhosis
C.Torti,E.Focà,A.d’Arminio‐Monforte,F.Dabis
• TrendsinmortalityaccordingtoHCVserostatusinpatients
infectedwithHIVintheeraofcARTinWesternEurope
J.delAmoandJ.Berenguer
1
10/9/2014
INCIDENCE AND PROGNOSIS OF
AIDS-DEFINING CANCERS IN THE
ERA OF CART: SOUTHERN AFRICA,
EUROPE AND NORTH AMERICA
COMPARED
COHERE SC MEETING
Julia Bohlius, Natascha Wyss & Matthias Egger,
Institute of Social and Preventive Medicine (ISPM),
University of Bern, Switzerland
Sitges, March 27th 2014
• Originally:
• To compare incidence rates, survival and the impact of cART in
HIV-infected patients developing KS, ICC and NHL in Southern
Africa, Europe and North America.
• Amended to:
• To compare incidence rates and the impact of combination
antiretroviral therapy (cART) in HIV-infected patients developing
Kaposi sarcoma (KS), non-Hodgkin’s lymphoma (NHL) and
invasive cervical cancer (ICC) in Africa, Europe, America and
Asia/Pacific. If feasible we will analyze survival of patients
diagnosed with cancer.
Kaposi Sarcoma incidence rates
in patients on cART
Data retrieval completed
NA-ACCORD
28,877
Objectives
COHERE
269,636
Europe
Adults: 123 / 100,000 pys
Taiwan
17,681
Taiwan
Adults: 133 / 100,000 pys
TAHOD &
TApHOD
12,952
CCASAnet
5,092
CROI 2014 Abstract
IeDEA-SA
570,829
Southern Africa
Adults: 173 / 100,000 pys
Children: 59 / 100,000 pys
AHOD
3,572
New concept sheet
Incidence and risk factors for developing Kaposi Sarcoma in the era of
combined antiretroviral therapy in Europe
Objectives
1.
To establish the incidence rate of KS in HIV-infected patients on cART and
not on cART in different European regions (Northern Europe, Western
Europe and Southern Europe).
• We will use the same definition of incident KS cases across cohorts. I.e. incident cases will be
defined as KS diagnosed > 30 days after enrolment. KS cases diagnosed within the first 30 days
of cART will be considered as not on cART. For a sensitivity analysis we will use day 0 and day >
14 as cut offs for the definition.
2.
3.
To assess the impact of cART and type of cART regimen on reducing the
KS incidence in the era of cART. We will investigate changes over time.
To identify risk factors and patient groups at increased risk of developing
KS with a focus on patient groups with reportedly high HHV-8 prevalence
rates (i.e. MSM and migrants from HHV-8 endemic regions). .
1
10/9/2014
New concept sheet
Acknowledgements
Incidence and risk factors for developing Kaposi Sarcoma in the era of
combined antiretroviral therapy in Europe
• Cancer Writing Group
•
Robert ZANGERLE, Massilios PAPARIZOS, Vincent LE MOING, François RAFFI, Fabrice BONNET, Geneviève CHENE,
Jesper GRARUP, Ana VERBON, Maria PRINS, Martin FISHER, Diana GIBB, Gerd FATKENHEUER, Julia DEL AMO,
Objectives, continued
4.
To identify short and long term risks of developing KS and changing risk
factors over time in patients on cART. We will consider the following time
windows after starting cART: 30 to 90 days, 90 days to 6 months, 6 months
to 1 year, 1-2 years and 2-5 years and 5-8 years.
5.
To identify the short term risk of developing unmasking KS-IRIS we will
repeat the analysis outlined in objective 4 and define all unmasking IRISKS as any KS in patients on effective cART diagnosed within the first 6
months of cART.
6.
To identify the long term risk of developing KS in patients on cART with
suppressed HIV-RNA load.
Clàudia FORTUNY, Niels OBEL, Amanda MOCROFT, Francois BOUÉ, Sophie GRABAR, Timo WOLF, Patricia GARCIA
DE OLALLA, Firouze BANI-SADR, Andrea ANTINORI, Anja POTTHOFF, Norbert BROCKMEYER, Eugenia QUIROSROLDAN, Cristina MUSSINI, Claudia FORTUNY, Jordi CASABONA, José MIRO, Laurence MEYER, Vincenzo
SPAGNUOLO, David NADAL, Barbara HASSE, Stéphane DE WIT, Bernardino ROCA, Julia BOHLIUS, Matthias EGGER,
Natascha WYSS
• Regional co-ordinating centers
•
Bordeaux RCC cohorts: Diana Barger, Celine Colin, Geneviève Chêne (Head), Christine Schwimmer, Monique Termote
•
Copenhagen RCC cohorts: Maria Campbell, Nina Friis-Møller, Jesper Grarup (Head), Jesper Kjaer, Dorthe Raben
• Sources of funding
•
The COHERE study group has received generic funding from: Agence Nationale de Recherches sur le SIDA et les
Hépatites Virales (ANRS), France; HIV Monitoring Foundation, the Netherlands; and the Augustinus Foundation, Denmark.
•
COHERE receives funding from the European Union Seventh Framework Programme (FP7/2007-2013) under EuroCoord
grant agreement n° 260694. A list of the funders of the participating cohorts can be found on the Regional Coordinating
Centre websites at http://www.cphiv.dk/COHERE/tabid/295/Default.aspx and http://etudes.isped.u-bordeaux2.fr/cohere.
•
Project specific funding from Swiss National Science Foundation.
2
10/9/2014
PROJECTS
•
COHERE Steering Committee Meeting
Sitges March 27, 2014
OI Working Group
Optimal timing for starting cART in antiretroviral-naïve HIV-1–infected
patients presenting with cryptococcal meningitis (J.M. Miro, J. Sterne, H.
Furrer)
–
–
–
•
Optimal timing for starting cART in antiretroviral-naïve HIV-1-infected
patients presenting with central nervous system (CNS) toxoplasmosis
(J.M. Miro, J. Sterne, H. Furrer)
–
!Wait for the summer!
•
Evaluation of guidelines for prophylaxis of opportunistic infections in
the era of cART" (J.M. Miro, H. Furrer)
•
Immune recovery after starting ART in HIV-infected patients presenting and
not presenting with opportunistic infections at the start of cART
History of tuberculosis as a risk factor for developing opportunistic diseases
after starting antiretroviral treatment in HIV-infected patients
Role of current HIV RNA as a CD4 independent risk factor for tuberculosis
incidence in HIV-infected persons
•
•
COHERE, ART-CC, CNICS and NA-ACCORD
major endevaour organising chart review
First results poster IWHOD
Postponed until crypto project above proves feasible
COHERE OI
All start with 2014 merger
1

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