The Parelsnoer Institute: A National Network of Standardized Clinical Biobanks in the Netherlands

Project description

In 2007, the Netherlands Federation of University Medical Centers (NFU) launched the Parelsnoer Institute (PSI) [1], with the aim of facilitating medical research and innovation ultimately leading to better diagnosis, treatment or even prevention of complex disorders [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17]. PSI is a collaborative network of all eight Dutch University Medical Centers (UMCs), also known as academic teaching hospitals. Figure 1 describes the organization of the Parelsnoer Institute. Basically, PSI consists of three dimensions: participating institutions (the 8 UMCs), disease entities (currently 15 disease specific groups which are called ‘Pearls’, still expanding) and the central organization with several expert areas. An executive board for operational management (see Figure 1) instigates collective strategic and tactic policies. In addition, a central team of PSI experts and advisors, working in the participating UMCs, supports the researchers and the board in establishing and implementing standards and procedures.

Figure 1

Several standard operating procedures (SOPs), regulations and agreements constitute a framework of ready to use harmonized standards throughout the subsequent phases of the biobanking process. Templates provide tools for efficient implementation of the SOPs and use of these templates contributes to the level of standardization. Application of this framework by all UMCs yields large uniform collections and contributes to high quality at all levels.

Each UMC stores biomaterials in their own certified biobank(s) according to the PSI biobanking protocol, which was developed by biobank coordinators from all UMCs together and covers all phases of biobanking. Each Pearl provides a different variety of biomaterials such as serum, plasma, DNA, faeces, urine, cerebrospinal fluid, pancreatic cyst fluid, viable cells, fresh frozen tissues and/or FFPE tissues. Metadata (e.g., type of material) from biomaterials and the unique sample code are registered in the central database together with the clinical data [18].

For each Pearl a specific information model is defined for the detailed clinical dataset including personal data and clinical data pertaining the specific disease [19]. The data are collected both via electronic and manual methods and are hosted in a validated web based application (ProMISe) that fulfills international standards for data management, quality assurance, and privacy protection using a Trusted Third Party [20, 21].

Classification (1)

Human.

Classification (2)

Biological samples and associated clinical data.

Context

Steps

For each Pearl a specific information model is defined, called PRISMA: Parelsnoer Repository for Information Specification, Modelling and Architecture. PSI adheres to the principle of reusing electronic health record (EHR) information for scientific purposes (“registration at the source”, http://www.nfu.nl/programma/registratie-aan-de-bron/programma). Therefore, PRISMA is developed with reuse of information and with minimization of registration burden as prime directives, while also taking routine care procedures into account. The architecture is in compliance with (inter-)national classifications such as International Classification of Diseases and Related Health Problems (ICD-10), SNOMED CT and the Logical Observation Identifiers Names and Codes (LOINC®).

Each Pearl defines its own set of biosamples to be collected and stored in the biobank. Biomaterials are preferably collected during routine clinical procedures. Samples are stored in certified UMC biobanking facilities which collectively constitute the federative PSI biobank. The biobanking protocol of PSI is implemented in all the participating institutions and covers all phases of biobanking; from collection to storage of the samples. Metadata (e.g., type of material) from biomaterials and the unique sample code are registered in the central database together with the clinical data. The detailed clinical dataset includes personal data (e.g., age, gender, education level, ethnic origin, weight, height) and clinical data pertaining the specific disease (e.g., diagnosis, lab results, complications, physical examination, (medical) treatment, questionnaires). The data are collected both via electronic and manual methods and are hosted in a validated web based application (ProMISe) [20].

PSI also provides an infrastructure and procedures to uniformly collect and store images, for instance MRI images. Standardized source images are safely stored in the local Picture Archive and Communication System (PACS) in the UMCs. After anonymization, the images are subsequently uploaded in the TraIT Bio-Medical Imaging Archive (BMIA), which is a safe and sustainable online archive [22].

Stabilization/preservation

Table 1 gives a summary of procedures on collection, processing and storage of samples defined in the biobanking protocol of PSI.

Type of long-term preservation

See Table 1.

Storage temperature

See Table 1.

Shipping temperature from patient/source to preservation or research use

See Table 1.

Shipping temperature from storage to research use

–80°C (on dry ice).

Quality assurance measures

Quality of data and quality of stored biomaterials are by no means self-evident. In PSI, the two most important critical success factors for adequate data quality are: to limit the number of elements in the information model to what is necessary for future research and to fully integrate the collection of data in the routine of the EHR. Other essential elements for adequate quality are: use international standards (Detailed Clinical Models), develop simple and logical instructions for data collection and registration, mandate and authorize dedicated research employees, and perform regular quality checks.

For biomaterials there is no possibility to improve quality afterwards. Only a strict adherence to the biobank protocol and related SOPs can assure quality of material available for research. This is under the assumption that SOPs describe (either evidence or consensus based) what is optimal for integrity of the biomaterials. In PSI, biobank coordinators from all UMCs together have developed the PSI biobanking protocol and revise them every two years. This involvement of all biobank coordinators in establishing the protocol enhances adherence to the described procedures. The PSI biobanking protocol covers all phases of biobanking: collection, pre-analysis, registration, processing and storage of the samples (Table 1).

Source of associated data

The associated data are mainly coming from electronic health records, laboratory reports, and questionnaires. Each UMC has its own research IT infrastructure that delivers the data to their local database in ProMISe, which is a web based application. In some UMCs data are entered manually into the local database (mostly by research nurses and/or clinicians) while other UMCs benefit from automatic data capture directly from the EHR resources. The information supplied by each UMC is periodically uploaded, after validation, to the central database in ProMISe (one database per Pearl, which is the combination of the 8 local UMC Pearl databases) for storage on a national level (Figure 2). During upload of data to the local and central databases, identifying data are encrypted by special software of a Trusted Third Party (Trusted Reversible Encryption Service®, Houten, Utrecht, The Netherlands). As to further protect the privacy of the patients, the identifying data are encrypted again when exported from the central database for delivery to the researchers. In specific situations, e.g., in case of incidental findings that need feedback to the patient or necessary data-linkage, depseudonymization is possible by authorized personnel only. The PSI IT infrastructure is compliant with international security and privacy standards.

Figure 2

Object name

The Parelsnoer Institute.

Bioresource name

The Parelsnoer Institute (PSI).

Bioresource location

All eight University Medical Centers across the Netherlands participate in PSI:

1. Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

2. Erasmus Medical Center, ’s-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

3. Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands

4. Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands

5. Radboud University Medical Center, Geert Grooteplein-Zuid 10, 6525 GA Nijmegen, The Netherlands

6. University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

7. University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands

8. VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands

Bioresource contact

Parelsnoer Institute, Jaarbeursplein 6, 3521 Al Utrecht, The Netherlands.

Email: info@parelsnoer.org

Bioresource URL

http://parelsnoer.org/page/en/Home

Identifier used

N/A.

Bioresource type

PSI is a collaborative clinical biobank, comprising a number of disease specific national bioresources (the Pearls). All types of pathology and disease samples are stored (see Table 1). To date (October 2016) the following fifteen disease categories are included:

• – Abdominal aortic aneurysm

• – Congenital heart disease

• – Cerebrovascular accident

• – Diabetes

• – Hereditary colorectal cancer

• – Inflammatory bowel disease

• – Ischemic heart disease

• – Leukemia, myeloma and lymphoma

• – Multiple endocrine neoplasia

• – Neurodegenerative diseases

• – Oesophageal and gastric cancer

• – Pancreatic cancer and pancreatitis

• – Renal failure

• – Rheumatoid arthritis and arthrosis

• – Parkinson’s disease

Type of sampling

PSI consists of disease based cohorts with longitudinal collections, sampled in clinical care.

Anatomical site

The fifteen Pearls cover several anatomical sites of the human body.

Disease status of patients/source

See the fifteen Pearls/diseases mentioned above.

Clinical characteristics of patients/source

A full clinical characterization, including extensive diagnostics, demographics, therapeutics and clinical follow-up is specified for each disease specific bioresource.

Vital state of patients/source

All patients are alive at inclusion.

Clinical diagnosis of patients/source

PSI covers several significant diseases, presently fifteen: Abdominal aortic aneurysm, Congenital heart disease, Cerebrovascular accident, Diabetes, Hereditary colorectal cancer, Inflammatory bowel disease, Ischemic heart disease, Leukemia, myeloma and lymphoma, Multiple endocrine neoplasia, Neurodegenerative diseases, Oesophageal and gastric cancer, Pancreatic cancer and pancreatitis, Renal failure, Rheumatoid arthritis and arthrosis, Parkinson’s disease.

Pathology diagnosis

The architecture is in compliance with (inter-)national classifications such as International Classification of Diseases and Related Health Problems (ICD-10), SNOMED CT and the Logical Observation Identifiers Names and Codes (LOINC®).

Control samples

The Parelsnoer Institute does not collect control samples from healthy individuals. If needed controls can be obtained from LifeLines, a national longitudinal population biobank in the Netherlands [24].

Biospecimen type

Each Pearl provides a different variety of biomaterials such as serum, plasma, DNA, RNA, faeces, urine, cerebrospinal fluid, pancreatic cyst fluid, viable cells, fresh frozen tissues and/or FFPE tissues. Table 1 gives a summary of procedures on collection, processing and storage of samples defined in the biobanking protocol of PSI.

Size of the bioresource

In total, clinical data of more than 32,000 patients and 538,000 biospecimens of more than 30,000 patients are available. PSI has no end date. The current number of included patients per Pearl is shown in Table 2.

Release date

Data and samples are currently available. PSI releases data and samples to research projects on a regular basis. Thus far, the research projects have led to many scientific publications [3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17]. ].

Access criteria

A catalogue, i.e., an open access searchable database on the internet, provides up-to-date information about the content of all PSI collections [18]. This gives researchers the opportunity to discover for what type of patients which type and amount of data and biomaterials are available. Every researcher worldwide may submit a study proposal to the Pearl and request data, biomaterials and/or images.

A scientific committee of the Pearl (consisting of representatives of the Pearl and independent scientific experts) judges whether the proposed study is relevant, compliant with the scientific aims of the Pearl, methodologically sound, compliant with privacy protection rules and feasible in relation to the amount of biomaterial requested. In addition, permission from the Research Ethical Committee of the coordinating UMC has to be obtained and from some other participating centers according to local policy. When permissions have been granted and request forms are completed, the PSI data manager will deliver the data (and images if needed) from the central PSI facilities to the researcher. The biobank coordinators of the UMCs will deliver the requested biomaterials. If scientific analyses in research projects yield new data, PSI demands these newly acquired (individual) data to be made available for future research purposes.

Costs vary depending on the type and amount of samples. An economic quotation is sent covering shipping costs and partially costs for biobanking-related services (sample handling, consumables).