BBMRI-NL awards thirty-four Complementation projects

9

Table of contents

Complementation Projects 2013 1 Rainbow project 11 2 UMC Biobanks: UMCU 4

News and Agenda 7

Column: Peter Kapitein 8

The GEOlynch project team, fltr: Fränzel van Duijnhoven, Lisette Kamps and Ellen Kampman

Hub

The concept behind BBMRI-NL’s Complementation projects remains the same: small-scale projects, improving the accessibility of existing biobanks for biomedical research by either enriching or harmonizing the materials or infrastructure. This concept has proven highly successful in the previous years, yielding publications in renowned journals and facilitating international research collaborations (for an example, see the news item on Dr. Leen ’t Hart’s diabetes paper on p.7).

This year’s contenders offer a wide range of topics, as do the biobanks they aim to improve: from AIDS to kidney disease, and from cardiovascular disease to psychiatric disorders. Applications were sent in by the eight UMCs, NKI, PALGA, and WUR.

Among this year’s awarded projects are:

CP58: Enrichment of the GEOLynch cohort by completing the established biobank - WUR: GEOLynch cohort study, Dr. F.J.B. van Duijnhoven

“The purpose of this complementation project is twofold. 1: to complete the biological material (blood) that is missing for part of the GEOLynch study, a prospective cohort of Lynch Syndrome carriers. From every participant in the GEOLynch study information about nutrition, lifestyle, anthropometry, medical history and a

DNA sample from saliva is available. The participants that have been recruited through the Radboud University Nijmegen Medical Centre (RUNMC) in Nijmegen (19%) also donated a blood sample. In the proposed project, we would like to collect a blood sample from the remaining participants (81%) ; 2: to set-up a biobank management system to be able to quickly locate our samples, to assess how much sample is left and to evaluate which lab analyses have been done per sample. This will improve the user-friendliness of our biobank and facilitate collaboration with other biobanks.”

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BBMRI-NL

awards

thirty-four

Complementation projects

BBMRI-NL has granted funding to 34 Complementation projects in its 2013 call. Six of the projects are dedicated to improving biobanks’ ICT infrastructure; this is the first time BBMRI-NL has put out a call specifically for projects focusing on bioinformatics and computer technology. All in all, the projects will receive funding for circa 1.7M€.

Morris Swertz and David van Enckevort: “Prepare the BBMRI-NL catalogue for connection to European initiatives.”

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Rainbow project 11: Catalogue 2.0

“We hope to limit the amount of work

and increase the efficiency”

When Dr Morris Swertz filed a grant application for a BBMRI-NL Complementation project in 2010, the aim was not to build a catalogue of all biobanks connected with BBMRI-NL. But the scope of the project left some time and money available; and building a biobank catalogue was definitely on the to do-list of the then still new organization. So Catalogue 1.0 was built and launched. Nothing fancy: “Just the bare essentials, like name, topic, co-ordinator and type of biodata”, says Swertz. “In the back of our minds, we knew that someday, we would be able to build on that basis to create a really smart catalogue for researchers. That time has now come.”

As can be expected, Rainbow project 11 bears the simple title “Catalogue 2.0”. The plan, as co-project leader David van Enckevort (NBIC Biobanking Task Force) explains, is “to build and fill a catalogue that stores not only basic data, such as the biobanks’ name, address, coordinator, and parameters, but offers data on an aggregated level for as many biobanks as are willing to participate; we call it a ‘level 3’ catalogue. This catalogue will enable researchers to identify fairly quickly which collections of samples are compatible to their needs, and so enable and enhance biomedical research.”

To clarify, the term ‘level 3’ refers to a list drawn up in 2012 by the biobanking catalogue working group, a group that consists of all major cataloguing projects in the Netherlands (BBMRI-NL, PSI, LifeLines, CTMM, TraIT, Mondriaan, NBIC Biobanking Task Force, EU-BioSHaRE, and BBMRI-NL Rainbow project 5), now joined in the Rainbow project team. The biobanking catalogue working group got together for the first time in 2011, “so that we could all profit from one another’s experience and ideas, and avoid double—or triple, or quadruple—work”, Swertz explains. The group identified five possible levels of data sharing, based on a survey conducted among biobanks:

“1. Registry of Biobank sample collections: This

level lists available biobank sample collections with a minimal set of properties such as ‘size’, ‘data topics’ and ‘material types’. It enables determining whether or not a certain dataset/biobank is relevant for your

research and contact the owner. Example: current

BBMRI-NL catalogue.

2. Data dictionary; Adds to level 1: information on data items available in each biobank collection

such as questionnaire questions, lab measurements,

diagnoses or GWAS arrays. This enables determining whether or not suitable data & material is available

for particular research. Example: P3G catalogue,

LifeLines catalogue.

3. Availability/aggregate data: Adds to level 2: aggregate information such as ‘number of available samples per data item’ or information on categories such as ‘number of high blood pressure cases’. This enables determining data on a sufficient number of participants is available for your research. Example: not found in the scope of the survey.

4. Individual Data: Adds to level 3: all individual observation data. This is effectively a complete set

of (anonymised) data in a biobank for which most

biobanks will have an in-house database. This enables creation of data sets from relevant subjects for research. Example: PSI, LifeLines.

5. Linked Data per Individual: This adds to level 4: services to link to data from other relevant sources

and registries such as the national cancer registry,

through pseudonimization service. This surpasses

single biobanks. Example: Mondriaan catalogue.”

(Catalogue 2.0 – and beyond, 2012) The survey also showed that most biobanks felt there was a need for a level 3 catalogue, ‘providing availability information on a limited set of variables to enable researchers to quickly find suitable sample sets for their research’ (Swertz et al). Van Enckevort: “Most biobanks felt that levels 4 and 5 were taking matters too far, because the participants’ privacy could not be guaranteed.”

Catalogue 2.0 is to be a flexible instrument, catering for the needs and possibilities of the 200 biobanks that are associated with

BBMRI-NL. Swertz: “For some biobanks, a level 1 or 2 registry is all that we can hope for right now. Other biobanks are far more advanced—for instance, Mondriaan is a level 5 registry. Some biobanks have their own catalogue, like PSI and LifeLines; it should be possible for them to link their information into the BBMRI-NL catalogue automatically, so that the information in the catalogue is always up-to-date.”

International connection

“We would like to offer so-called data counts of twelve variables to those biobanks that are interested”, Swertz continues. “So what biomaterials are available, but also which protocols were used to process them, what types of lab work have been performed? It’s all pretty experimental right now, but we hope to prepare the catalogue for connection with initiatives that are currently developing in Scandinavia (BBMRI-NORDIC) and throughout Europe (BioMedBridges), via BBMRI Europe.”

Apart from making biobanking data more readily accessible to researchers, the Rainbow project team also wants to simplify matters for the people working in

the biobanks, for instance by linking data sharing request forms or order forms to the data. Van Enckevort: “Offering extra functionality will limit the amount of work and increase the efficiency for all parties involved.”

Eager as the team is to build the most sophisticated catalogue possible, they are aware that they have to overcome some hurdles. Van Enckevort: “The reactions we encountered when we held the survey were mixed. Some people couldn’t wait and were highly optimistic; others just didn’t see the point; and yet others feared that their data would not be safe. It is our job to take away their fears and build a reliable and useful catalogue.” Swertz adds: “Our biggest hurdle will probably not be convincing biobankers that the catalogue is a useful tool, but overcoming organizational and technological challenges.”

“For instance, who will be responsible for the extraction of data? How do you keep the information up-to-date? And how do you realize different sets of rights and access levels?” Van Enckevort interjects: “We will have to do some serious mapping to integrate the several kinds of terminology

Fokke Terpstra, Biobank manager at the UMC Utrecht: “The UMCU Biobank is a collaborative effort of the biobank and the researchers involved.” (photo: Thijs Rooimans)

UMCU: Moving towards

a centralised biobanking

facility

“The String of Pearls Initiative PSI has given a strong impulse towards a more centralised, UMC-wide approach”, says Fokke Terpstra, Biobank manager at the UMCU. “When I came here in 2008, the main challenge was to set up our contribution to PSI. We wanted to incorporate all the ‘pearls’ into a larger whole, avoiding the situation that each pearl would have its own collection of materials and data. So we set up a central facility where we implemented the PSI protocols. As you know, all eight university medical centres participate in PSI. Together, we agreed on the rules of the game. In Utrecht, we thought that these rules were a good basis for all biobanking activities within our centre, so our work in PSI was also the groundwork for our own set of rules. Whenever someone wants to

establish a new biobank, they first have to apply for approval to the medical ethics committee, the METC. One of the criteria they have to meet is that their basic setup will be similar to PSI.”

“Of course there is always room for discussion with respect to the final protocol. We try to convince the researcher that the central biobank facility is beneficial in terms of trust, quality, cost effectiveness, and optimal service; the UMCU Biobank is a collaborative effort of the biobank and the researchers involved.”

Release protocol

As Terpstra explains, a biobank differs from other medical experiments involving patients’ materials in that there is no clearly defined scientific question. Materials

and data are collected as an investment in future research. This makes it difficult for a medical ethics committee to evaluate the plans for a new biobank. By definition, it is unknown what exact scientific needs will be served by the collection of materials and data. “That is why we have chosen to build a two-step system. The METC evaluates the plans beforehand: according to the criteria of the law on medical experiments (WMO, wet medisch-wetenschappelijk onderzoek met mensen) in case of medical intervention; or in other cases the METC provides the researcher with a non-WMO statement.”

“Then, once there is enough material in the biobank to make it interesting for researchers, there will be applications for materials and/or data. These requests will be evaluated by our special scientific advisory board. They do not have to perform the medical ethics evaluation all over again, but they will have to make sure that the materials will be used for sound scientific purposes.” In the nearby future, the current advisory board will become a special chamber of the medical ethics committee. This chamber for biobanking will evaluate both the new initiatives on biobanking and the release of materials and data to users.”

Talking about the release of materials, Terpstra explains how there are strict rules on the use of materials by external research partners: “Use by researchers outside the UMCU is only allowed if one or more researchers of UMCU participate in the study and take responsibility for the proper use of materials by outside partners. So if researchers from a university or a company approach me, asking for materials from our biobank, I will tell them they have to find a researcher within UMCU who will be their liaison. As a hospital, we owe it to our patients to be very careful and diligent in dealing with their materials. As I heard someone say at a biobanking congress: ‘If financial bankers had been as reliable and honest as biobankers, the current financial crisis would not have happened’.”

According to Terpstra, the UMCU may charge commercial partners a modest fee for storage and retrieval, but he cautions against commercialisation of a university biobank: “People have given these materials for free, as their contribution to medical science. I think it would be unethical to make a profit from these materials. All we

can consider is asking a contribution that will allow us to continue our scientific work.”

Centralisation

It is the intention of the board of directors of UMCU to move all existing biobanks to a central facility. At the moment, Terpstra and his colleagues are looking for a convenient space for the many freezers. They also are calculating the risks of centralising all samples without some backup elsewhere. “We already know that the Netherlands are one of the safest countries in the world, also if it comes to longer lasting power outages. But although a -80° freezer will stay cold for more than an hour without power, any longer outages could be disastrous, so we need to have extra emergency generators for our storage facility. And then, there’s what I call the Boeing scenario. We need to consider the possibility that some unforeseen disaster strikes, like the Boeing that hit an apartment building in Amsterdam 21 years ago. We still have to calculate the risks and decide what level of certainty we need.”

Not every collection of tissue samples will make it to the new central facility. In some cases, the quality of materials and/or the accompanying data simply is not good enough. “If a collection does not meet our quality criteria, we have to seriously consider the possibility of just destroying it. On the other hand, there are interesting examples of inferior collections that still served a major scientific purpose, like those tissue samples from the 1960s in Africa that were badly damaged, but good enough to demonstrate the presence of HIV sequences. So even if the quality is bad, you have to be cautious what you throw away.”

Part of the centralisation effort is a major operation to connect all data files within UMCU, while maintaining optimal privacy. Again stimulated by the PSI, information technology experts have succeeded in building an infrastructure that provides a rich treasure trove of data. As every sample of biological materials is stored in a tube with a unique bar code, it will be easy to find relevant data without violating the privacy of patients. Terpstra sounds proud when he talks about this project: “A lot has been achieved in the past years. I’m confident that our biobank will contribute to major scientific discoveries in the coming years and decades.”

By Pieter van Megchelen

Several years ago, the University Medical Centre Utrecht was the first UMC to install a special scientific advisory board to deal with requests for biobank materials and data. A central facility for storage is in the making, and the logistics for data storage and retrieval are being optimised. All new UMCU biobank initiatives have to adhere to the quality standards and regulations that are now in place. In the future, all UMCU biobank collections will be part of the central biobank.

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used by different biobanks to describe, for instance, biodata.” Swertz: “All these issues have to be pondered carefully and addressed in procedures. Up to a point, the catalogue will be custom made, even though it is based on the Molgenis software already in use for the current BBMRI-NL biobanking catalogue, CTMM, LifeLines, and the Genome of the Netherlands Rainbow project.” The project has already gotten off to a flying start. Swertz: “In a way, this project started when we started work on the first catalogue. A lot of advance work was done then. The biobanking catalogue working group paved the way for the next step; it’s a natural progression, you could say.” Van Enckevort: “What we are embarking on now is expanding the Molgenis software. After that, a pilot to see how and if everything works properly is planned, with a small coalition consisting of LifeLines, Prevend, PSI and CTMM as ‘guinea pigs’. These studies will feed their aggregated data into the catalogue and test the new functionalities.”

Catalogue 1.0

If you are a researcher / biobanker and interested in the BBMRI-NL biobanking catalogue, you can apply for a login for the current catalogue. This gives a general insight in the some 200 biobanks associated with BBMRI-NL.

“The first year will probably be spent on that. The second and third year we will use to facilitate all associated biobanks to upload their data, and teach them to use the new catalogue; for instance, they will be able to add new information themselves, a functionality that was absent in catalogue 1.0, and will increase efficiency.”

> Complementation projects, continued from page 1 CP65: Enrichment of the multicenter Dutch Hodgkin’s Lymphoma Cohort to study susceptibility genes for the development of adverse late effects of treatment - NKI: Dutch Hodgkin’s Lymphoma Cohort , A.W.J Opstal-van Winden, A. Broeks, B.M.P. Aleman, F.E. van Leeuwen

“In the Dutch Hodgkin’s Lymphoma Cohort (n=7400) we investigate the late effects of the treatment of Hodgkin’s lymphoma (HL). We aim to identify treatment-related risk factors and their interactions with genes and lifestyle for a broad spectrum of late side effects. The results of this research can be used to personalize the treatment of HL patients in the future and, for patients treated in the past, to identify high risk groups for specific late adverse effects of treatment. The aim of this project is to collect DNA samples of 5800 patients for whom these are not available yet. This will enable us to investigate genes that modify the risk of treatment-related late effects nationwide, but will also facilitate international collaboration.”

CP86: Reconnaissance of a national registry facilitating: ‘opt out’ for further use of residual tissue - PALGA, Dr. I. Nagtegaal “This complementation project aims to evaluate the feasibility of a national online registry for opt-out registration for further use of residual tissues. The idea would be to eventually create a national registry where all patients and future patients can indicate that they want to opt-out for further use of their stored residual tissues, and which biobank custodians and researchers can consult before handing out stored residual samples to researchers. This obviates the need for caregivers to maintain a separate registry for opt-out and avoids patients being questioned every time they enter another care facility. An online registry offers an easy point of access to file withdrawals. In addition, patients will be able to access the registry themselves. Should the outcome of the project be that such a registry is (legally and otherwise) feasible, a project will be set up for the actual building of the registry.”

Early Bird discount for HandsOn: Biobanks 2013

If you register for HandsOn: Biobanks 2013, 21-22 November at World Forum, The Hague before 31 August, you receive a sizeable Early Bird discount. Students are also eligible for a reduced fee. Go to www.handsonbiobanks.org/2013 and check it out! Program details can be found on the website. So far, confirmed speakers are: John Wilbanks, Jan Velterop, Peter Kapitein, David Porteous, Nasrin Perskvist, Kay Parkinson, Ele Zeggini, Jan-Eric Litton, Cees Smit, Peter-Bram ‘t Hoen, and GertJan van Ommen. Major publications for BBMRI-NL projects

Two BBMRI-NL Rainbow projects publish on their progress this summer, both in leading journals. Rainbow project 1, Genome of the Netherlands (GoNL), has a paper online now in the European Journal of Human Genetics called ‘The Genome of the Netherlands: design, and project goals’ (2013, Boomsma, Wijmenga, Slagboom et al). Rainbow project 3, A nation-wide functional genomics infrastructure enabling mechanistic insights into complex disease phenotypes, publishes a paper in Nature Reviews Genetics in August with the title ‘From promises to practical strategies in epigenetic epidemiology’(2013, Mill & Heijmans).

DNA-variant affects diabetes risk and medicine effectivity

Research, co-funded by BBMRI-NL, has proven that a DNA-variant near the gene for a digestion enzyme not only affects the risk of developing diabetes, but also has an influence on the effectivity of diabetes medication.

Dr. Leen ‘t Hart (LUMC) describes the research he conducted together with the VU medical center and Danish, German, British, and Swedish researchers in the May 15 issue of the scientific journal Diabetes.

First keynote for HandsOn: Biobanks 2013 confirmed

Professor Katherine Payne will appear as keynote speaker on 22 November at HandsOn:Biobanks 2013. Her topic: Biobanks and Health Economy. Professor Katherine Payne holds a personal chair in health economics at the University of Manchester (UK). She has over 16 years experience as an academic health economist and an international reputation for the economics of genetic technologies and services.

Agenda

To submit your event to the agenda, send an email to [email protected], stating the name of the conference plus date, venue and a short description of the programme.

LifeLines First Scientific Symposium - University Medical Center Groningen, 3 July

LifeLines is one of the most valuable, multidimensional cohort studies and biobanks in the world. It is the largest population based study in The Netherlands, with 165.000 individuals which will be followed-up for 30 years. To show how biobanks, and specifically LifeLines, can benefit your research, LifeLines presents its first scientific symposium on July 3 in the UMCG. Connected to this symposium we make a free data set available for the most innovative research idea. More information, program and registration form can be found on http://www.wenckebachinstituut.nl.

BBMRI-ERIC, LPC and International Biobanking Summit - Alte Universität Graz, Vienna, 16/18 September

BBMRI combines three events: on Monday 16 September, the inauguration of the new legal entity BBMRI-ERIC will take place (check bbmri.eu for more information). The 17th sees the second edition of the BioSHaRE International Biobanking Summit (www. bioshare.eu). Wednesday 18 September BBMRI-LPC will host a forum meeting as a platform for information exchange between countries with advanced large population cohorts and countries who want to start setting up LPC’s. See www.bbmri-lpc.org. To register for this three-day event, send an email to [email protected]. You will be forwarded a personalized registration link. Registration is free, but limited: the deadline is 30 June.

ESBB Conference - Palazzo Gran Guardia, Verona, 9-11 October 2013

The 2013 conference of the European, Middle Eastern & African Society for Biopreservation and Biobanking will be held in collaboration with BBMRI Italy. More details to follow soon. See http://www.esbb.org

CMSB Symposium - Stadsgehoorzaal, Leiden, 14/15 October

CMSB celebrates its second lustrum in this two-day symposium, which will showcase ten years of academic brilliance leading to discoveries in the five main CMSB research programme diseases. See http:// www.cmsb.nl

Colophon

Hub 9, June 2013 Hub is the official

newsletter of BBMRI-NL (Biobanking and Biomolecular Research Infrastructure). It appears in a circulation of 1,000 copies and as a pdf on the BBMRI-NL website. To subscribe to Hub, email [email protected] or register on www.bbmri.nl/ en-gb/news/newsletter/ subscribe-to-printed-newsletter. Subscriptions are free. Editorial board: Margreet Brandsma

Petra van Overveld Gert-Jan van Ommen Nicole van Scherrenburg Ronald Stolk Cisca Wijmenga Gerhard Zielhuis Editor-in-chief: Margot Heesakker-Heintz ([email protected]) Contributions to this issue:

Pieter van Megchelen

Peter Kapitein Photography:

Ivar Pel

Thijs Rooimans

Lay-out:

Margot Heesakker - Heintz

Print: Printshop Ouwehand

BBMRI-NL is part of BBMRI

and is funded by the Netherlands Organisation

for Scientific Research (NWO).

Peter Kapitein: Let

patients decide for

themselves.

Save my tumour - it might

save your life!

“Save my tumour - it might save my life.” I heard that while talking to George Coukos in Lausanne. The discussion was about using tissue for the research into cancer. Samples of human tissue, such as skin, cells, blood and saliva, are needed for research. George is a great advocate of taking tissue and freezing it for later use in research. Freezing it and not placing it in paraffin wax. As George explains, once it’s been put in paraffin wax it’s no longer useful. I was already a supporter, but even more so after the visit and the chat with George. Yet I’ve changed his statement slightly: “Save my tumour - it might save your life.”

You don’t store tissue just for the patient’s sake. You do it for the patients going to be treated in the future. Tissue is taken to enable research, but that research shouldn’t be limited to the person who donated the tissue. After all, patients always want to assist where they can in research. For everyone’s sake. It’s something everyone knows, yet an enormous number of restrictions are still being imposed. Not by patients though.

‘It’s unbelievable how much we’re being impeded by legislation and regulations.’ That’s grist to the mill to an anarchist like me; government has an unbridled urge to make laws and rules that restrict people. There’s not a lot we can do. But is that true? The Patient Advocates group of Inspire2Live had a good discussion recently with epidemiologists and pathologists from the Dutch Cancer Institute. And what emerged? There is not one official law or rule that impedes the removal of tissue from patients for use in research. Not even for future research. It´s simply a case of asking nicely. In other words, getting the patient´s consent. And all patients give their consent.

So where are these restrictions coming from? Is there really anything amiss? Of course there is. It´s the internal committees of the hospitals. They play the role of the patient and decide what may or may not be done. They get three people together to come to an agreement and make up some rules and suddenly the machinery grinds to a shuddering halt. Really. It’s incredible

what people submit as dangers, risks, fears. And they all have to be implanted into rules. And everyone knows: ‘Give people rules and they stop thinking’. We really have to fight this. Radical, I know. The patient decides and no one else. It’s their tissue.

It’s so simple. The patient goes to the doctor and the doctor asks if it’s all right to take an extra vial of blood for research. Now and in the future. When making a diagnosis, some tissue often has to be taken to determine if cancer exists and, if so, which type. So just ask if some extra tissue could be taken for research. Now and in the future. And the patient will say ‘yes’. Why? Because the patient understands there’s a big problem that needs to be solved. And let’s also ask patients who we know are going to die because there is no suitable treatment for them yet. I’m thinking of those suffering from pancreatic cancer, lung cancer caused by the tobacco industry and oesophagus cancer. One of the reasons there are so few treatments is that there has been little research carried out. Making tissue available can contribute greatly to this.

Every year 10 million people die of cancer. That must stop. And it’s going to stop. And to stop it, a lot more proper research needs to be done. Co-operation between patients, doctors and scientists will make this happen.

Peter Kapitein Never ever quit! Peter Kapitein is president and patient advocate at Inspire2Live, the international organization for the victory over cancer. He is also the ambassador for the Alpe d´HuZes fund raising effort for cancer treatment and research. Peter has been living with cancer since 2005. He is living proof that cancer is not always a death penalty, but can be the start of a new and richer life full of chances and beautiful people. BBMRI-NL is lucky to have secured Peter as a speaker at HandsOn: Biobanks 2013, www. handsonbiobanks.org/2013.

- by Peter Kapitein, Inspire2Live