Key words
register - multicentric data - quality assurance - data protection - prevention -
health service research
ADSR Arbeitsgemeinschaft Deutschsprachiger Schlaganfall-Register (Workgroup of German
Stroke Registries)
ATLS Advanced Trauma Life Support
BDSG Bundesdatenschutzgesetz (Federal Data Protection Act)
CI Cochlea implantation
CIO Chief Information Officer
DDR Deutschen Demokratischen Republik (German Democratic Republic)
DGHNO Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie
(German Society of Otorhinolaryngology, Head and Neck Surgery)
DNVF Deutsches Netzwerk Versorgungsforschung
DSGVO Datenschutz-Grundverordnung (General Data Protection Regulation)
EDC Electronic Data Capture
FAST Focused Assessment with Sonography for Trauma
GEKID Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. (German
Society for Epidemiologicl Cancer Registries)
GKR Gemeinsames Krebsregister (Common Cancer Registry)
IACR International Association of Cancer Registries
IQWiG Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (Institute
for Quality and Efficiency in Healthcare)
IT Information technology
KFRG Krebsfrüherkennungs- und -registergesetz (Cancer Screening and Registry Act)
MTP Monosyllable, Trochee, Polysyllable
RCT Randomized controlled trial
SGB Sozialgesetzbuch (Social Security Law)
TR-DGU TraumaRegister der Deutschen Gesellschaft für Unfallchirurgie (Trauma Registry
of the German Society for Trauma Surgery)
ZfKD Zentrum für Krebsregisterdaten (Center for Cancer Registry Data)
1. Introduction
In medical research, diverse study types exist that are classified into primary and
secondary research. In the context of secondary research, already existing research
results are summarized in review articles and meta-analyses. Primary research, however,
where trials are conducted, are subdivided into three main focuses of basic medical
research, clinical, and epidemiological research [1]. Epidemiological trials analyze the distribution and temporal change of the incidence
of diseases as well as their origins. In analogy to clinical trials, experimental
and observational studies are differentiated in epidemiology [2]
[3]. Epidemiological observational studies can be further categorized into cohort studies
(follow-up studies), case control studies, cross-sectional studies, ecological studies,
and descriptions with registry data. Healthcare research is a subdomain of healthcare
system research that is included in the limit area of clinical and epidemiological
research, public health research, and health economics. The German Network of Healthcare
Research (DNVF, Deutsches Netzwerk Versorgungsforschung, http://www.dnvf.de) currently
consists of 52 professional societies and 37 scientific institutes and research consortiums.
One exception is the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery
(DGHNO, Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie),
which does not belong to the member societies. The objective of the interdisciplinary
network is the methodical, content-related, and institutional development of healthcare
research and the elaboration of common strategies. The DNVF defines registries (etymology:
lat. registrum – directory, inventory, list, registry) as a possibly active, standardized
documentation of observation units about previously determined questions that may
be expanded in the further course, for which a precise correlation to the target population
may be described transparently [4]. Active, standardized documentation means that data assessment is performed prospectively
by staff belonging to the registry or specifically entitled. A high level of standardization
of all applied methods (data assessment, data entry, evaluation, reporting) is expected.
Observation units are single persons (patients or healthy subjects), groups (persons,
treatment institutions such as hospitals), or other entities (e. g. biomaterial).
All observation units of the registry emerge from the so-called source population
that has to be precisely characterized (e. g. based on the region, basic disease,
therapeutic measures, age, gender, period, exposition etc.). The group about which
a statement should be found is called target population. Ideally, the source population
of the registry is identical to the target population in the sense of external validity
(representativeness) [4]
[5]. Registries have to be differentiated from cohorts and randomized clinical trials
(RCTs). RCTs are experiments comparing diagnostic or therapeutic interventions with
a control procedure regarding a specifically selected patient group in a highly standardized
environment. RCTs are the gold standard for evidence of effectiveness and safety of
innovative therapies [6]. A cohort is a representative cross-section of subjects, e. g. birth cohort, school
enrolment cohort, or a cohort that is representative for the entire population. These
cohorts allow investigating the development of diseases, differences between sick
and healthy subjects as well as people with and without risk factors [7]. The largest and best-known cohort study is the Framingham Heart Study that since
1948 performs a systematic examination of the population of the town of Framingham
(Massachusetts, USA) with regard to origins and risks or coronary heart disease and
arteriosclerosis [8].
The term of “registry” emphasizes the data conserving aspect while cohort studies
are focused on knowledge gain. Registries include subjects with a certain disease,
such as for example midfacial fractures, or with a particular healthcare situation,
e. g. cochlea implantation (CI). The objective is a nearly complete or at least representative
image of the total population. Hence, a registry reflects the effectiveness of an
intervention of routine healthcare provision [9]
[10]. Another difference between cohort and registry is the implementation of data assessment:
a registry contains information and knowledge from regular patient healthcare without
performing interventions. In contrast, cohort studies only conduct the research project
under controlled conditions, own research staff, and defined investigators.
2. Objective of registries
2. Objective of registries
The objective of registries is the scientific assessment and analysis of healthcare
provision and the health status of the population. Disease-, product-, quality-, and
population-based registries may display the healthcare reality and its changes.
2.1. Description of epidemiological correlations and differences
Epidemiological, population-related registries are the most central data basis for
incidence, regional distribution, and temporal development of certain diseases in
the population (e. g. epidemiological cancer registries). In this way, prevalence,
incidence, or distribution and course of diseases are characterized, possible causes
of diseases are investigated, and the risk factors influencing the disease as well
as regional differences and temporal changes are identified [11].
2.2. Support of quality management and improvement
In Germany, quality management has a central significance due to legal requirements
anchored in the 5th Book of the Social Security Law (SGB V) [12]. The objective of the evaluations is the assessment and comparing description of
indicators that are directly or indirectly correlated with the quality of healthcare.
These comparisons allow conclusions regarding differences in the healthcare situation
(treatment quality, overuse, underuse, and misuse of healthcare services) and evaluation
of the quality of diagnostics and therapy with reference to guideline-based treatment.
2.3. Support of clinical research
Registries support clinical research by observing and evaluating the effectiveness,
safety, efficiency in the healthcare routine. Registry data may serve as basis for
clinical research: beside generating hypotheses and planning case numbers, registries
can be used as sampling frame [4]. Moreover, hybrid designs (RCTs plus registry) – also the combination of experimental
and observing investigations – provide the possibility of complementary addition by
embedding a small group of homogenous patients in a larger patient group in which
the effectiveness can also be measured in the healthcare routine [13].
2.4. Evaluation and monitoring of patient safety and effectiveness in healthcare provision
Due to their mostly high numbers of cases and long duration, registries present the
possibility to assess the occurrence of rare and/or delayed results, complications,
and/or drug interactions up to product defects in a statistically valid and significant
way. In addition, there is the option to achieve evidence on the safety within patient
groups that usually do not participate in clinical trials. Those include pregnant
women, children, older people, but also severely/mildly sick individuals and/or patients
with comorbidities/multimorbidity or accompanying medication [14]
[15].
2.5. Economic evaluation
Evidence on the effectiveness and efficiency of interventions can be found by means
of registries. One example is the utilization of certain medical services by patients.
In addition, registries provide health-economic data on specific interventions over
a longer period that otherwise could only be roughly estimated because of missing
evidence. The assumption of guideline-based therapy is another example [16].
2.6. Minimum quantities
A possible correlation between the number of surgeries performed in a hospital and
the mortality after the intervention was revealed for the first time in the US American
literature 20 years ago. The mortality in hospitals performing a high number of certain
interventions was lower than in those with low quantities [17]
[18]. In Germany, the principle of self-management is applicable. The government provides
the legal conditions and tasks; the insured and financially contributing parties as
well as the service providers, however, organize themselves in associations that are
self-responsible for medical care of the population [19]. According to the SGB V, a catalogue of predictable services shall be established.
Hereby, the quality of the treatment outcome depends particularly on the quantity
of the performed service. The Institute for Quality and Efficiency in Healthcare (IQWiG)
has already performed regression-analytic calculations for coronary surgery and knee
arthroplasty (www.iqwig.de). By analyzing the healthcare quality in dependence of
the frequency of interventions, registries may contribute relevantly to the establishment
of evidence-based minimum quantities.
3. Registry development
Registries are different with regard to their form, their assessment methods and tools.
Specific questions and objectives are an essential basis for the development of registries.
Beside financial, staff-related, and time resources of the research institution, the
knowledge of structural and processual conditions of national and regional healthcare
systems as well as legal and regulatory requirements have to be exactly defined. The
registry protocol documents the results of single steps according to internationally
acknowledged guidelines [20]
[21]
[22] and describes in detail all single phases of the procedure [4].
3.1. Planning phase
Beside the definition of the question, the objective of the registry for clinical
research has to be clarified in the planning phase. The data assessed in the registry
can be classified into the categories of patient, treatment, outcome, and general
conditions. The characteristics that have to be analyzed should be target values,
interesting influencing parameters, potentially disturbing factors (confounder/effect
modifier), or data required for administration. Inclusion and exclusion criteria define
the source population and the evaluation collective. Often, registries are planned
for large collectives. In the sense of a reflected use of resources, the basic principles
of sample size estimate should be taken into consideration. The assessment procedure
has to be defined with regard to type and number of evaluation centers, reporting
channels (paper-based, electronic, automated interfaces) as well as the duration and
organization of follow-up. Competence and responsibility referring to organization,
conduction, quality management, statistics, reporting, and publication have to be
determined previously. Secure financing of the registry presents a relevant part of
planning because it is essential for the later operation of the registry. Besides
financing by national public sponsors, foundations, cost bearers, or federal states,
generally also financing by industrial enterprises can be imagined. Financing of existing
registers will be elucidated in the paragraphs on the respective registries.
3.2. Draft phase
In the draft phase, the variables elaborated in the planning phase have to be implemented
in a logic data model. Essential variables or characteristics have to be differentiated
from less relevant ones because with higher data variety the risk of incomplete and
invalid datasets increases. The definition of indispensable core data elements ensures
a complete minimum dataset for all patients. Possibly resulting disregard of certain
variables may cause problems for later evaluation. The creation of respective assessment
documents and forms (electronic, paper-based), the definition of pseudonyms for pseudonymized
storage as well as the retention of identifiable data (registry central, registration
centers, trustees) have to be discussed. Data management serves for systematic organization,
quality assurance, and validation of registry data. To achieve a possibly high recruitment
rate, the inclusion of registry participants over several levels/healthcare pathways
(e. g. hospitals, practices, pharmacies) may be suitable. In order to realize a target
sample size with voluntary participation of patients and/or registry subjects, well-planned
strategies are essential for recruiting and sustainable motivation.
3.3. Implementation phase
Main objectives in the implementation phase are the renting of rooms, acquisition
of staff, purchase of hardware, realization of online applications, and contracting
with the assessment centers. The onset of the registry operation starts as soon as
the assessment centers are ready for recruiting and the registry central disposes
of the infrastructure and functions to include inscriptions.
4. Technical organization of a registry
4. Technical organization of a registry
The following different levels with clear interfaces to support the sustainability
of the registry are defined for the conception of the registry management [4].
4.1. Hardware
A registry should dispose of 2 servers. While the first server provides the productive
environment, the second one secures an identical environment for the case of the first
server’s failure.
4.2. Software
The selection of the appropriate software for systematic assessment is an elementary
aspect. The so-called remote data entry is a computer-based system for data entry
from the distance that is conceived for the assessment of electronic data. If the
registry pursued a defined reporting strategy similar to clinical trials, electronic
data capture (EDC) systems may be considered. However, if the registry intends patient-accompanying
documentation, a system with realization of electronic health records is suitable
[23].
4.3. IT management
Information technology management (IT management) should be conducted by a chief information
officer (CIO) with specific expertise regarding management and operation of computer-based
application systems in healthcare.
4.4. Registry operations
The main tasks of registry operations encompass the creation and maintenance of assessment
and presentation forms, user administration, data control, verification and correction,
providing trainings, dunning, archiving as well as generating regular reports.
4.5. Management
The management board represents the registry and requires a close connection to the
bearer. High levels of identification and experience with the specific objectives
of the registry are essential.
5. Evaluation
During the evaluation process of primary data, the application of mathematical-statistical
methods does not differ from other scientific investigations. Because of the complex
data structure, registries with repeated prospective data assessment (follow-up) and
inclusion via multiple institutions (multicenter) often require particular multivariate
methods of analysis.
5.1. Description
The primary work of a registry encompasses the socio-demographic and clinical characterization
(baseline description) as well as its treatment and outcome. Hints to statistical
precision or uncertainty of the results should be contained in the descriptive analyses,
preferably in form of confidence intervals. The data quality should be presented transparently
by mentioning type, frequency, and outcome of necessary queries, statements on data
concordance (congruence of registry and original data), and plausibility (consistency
of registry data) [24].
5.2. Methods for adjustment
Statistical results of group-comparing analyses can be biased by confounding or effect
modifying variables with unequal structures of the observed groups. Potentially existing
structural inequalities can be balanced by means of various control and/or adjustment
procedures [25]
[26]
[27]
[28]
[29]
[30].
5.2.1. Stratification/subgroup analyses
Stratification is defined as the classification of the registry collective based on
at least one potentially confounding or effect modifying variable in subgroups. Consequently,
regarding the stratification variables, the subgroups are equivalent or homogenous.
A rapidly growing number of subgroups and thus the increasing probability for incidental
findings with at the same time reduced power setting is a problem in the context of
this type of analysis.
5.2.2. Matching
Matching characterizes a procedure to form groups that are homogenous in at least
one potentially confounding or effect modifying variable. The comparability of the
groups increases with higher numbers of matching criteria. However, the identification
rate decreases for identical group members so that the analysis can only be performed
in a subsample of comparable group members. A balanced number of matching criteria
and size of the matched control group is essential.
5.2.3. Propensity Score
The propensity score is a statistical matching technique in order to control systematic
differences or biases between comparison groups so that the affiliation probability
to one group may be given.
5.2.4. Standardization
The subsequent adaptation of the result of stratified groups regarding a potentially
confounding or effect modifying variable with an identical stratified comparison population
is defined as standardization.
5.2.5. Multivariate modeling
Multivariate models allow the simultaneous definition of the relationship between
group and outcome. Potentially confounding or effect modifying variables may be integrated
in theoretically unlimited numbers as so-called co-variates (statistical control,
risk adjustment). Their effect on the outcome is then quantified in a statistically
correct way (effect adjustment).
5.3. Modeling of longitudinal data structures
In the context of evaluation of repeatedly assessed data, the dependence between multiple
assessments (follow-ups) has to be checked with statistical models for repeated measurements
or time-to-event models.
5.4. Adjustment for multiple statistical testing
The control of the type 1 error probability should be performed by respective adjustment
procedures, e. g. Bonferroni correction, in cases of repeated interim evaluation or
statistical test between several registry groups.
5.5. Control of cluster effects
Potential effects regarding reporting institutions such as hospitals vs. practices
or institutions with high or low reporting should be controlled by multi-level models
(e. g. hierarchic linear models) in registries with multicenter reporting structure.
5.6. Data mining
Data mining means the systematic application of statistical methods and procedures
of pattern recognition on registry data with the aim of identifying new interconnections
and trends of previously unknown correlations, independently from a hypothesis.
6. Reporting
Regular and current communication of the registry findings to all interest groups
is highly relevant. Feedback on the registry process optimizes the motivation of the
reporting institution as well as of the patients [4].
6.1. Feedback to reporting institutions
Regular feedback to the single reporting institutions should contain the quantity
and quality of the provided data. Furthermore, the interest situation with contents-related
evaluations together with “benchmarking” of the providing institutions should allow
a structured, indicator-related comparison of the performance. The therapeutic behavior
of involved reporting institutions can be influenced by feedback in the course of
registry operation.
6.2. Patient information
If the evaluations of the registry lead to potentially relevant findings for the individual
patient, this information can be forwarded to the reporting institutions involving
also the ethical commission or to the patient even including a trustee based on preliminary
regulations.
6.3. Public reports
Fundamental evaluation results of registries should be made available to the public
in a suitable way. In order to adequately answer questions on risk stratification,
the evaluation of the results to be published should involve the target groups (e. g.
patient organizations).
6.4. Scientific results
After checking and evaluating, relevant registry data should be made available to
science in form of congress contributions, publications, and annual reports. If interested
scientists need registry data, an application should be submitted to the registry
describing the aim of the investigation. According to the definition of type and extent
of the data as well as rights and obligations of the data recipient, they are provided
with an offline access.
7. Data Protection, Legal and Ethical Aspects
7. Data Protection, Legal and Ethical Aspects
7.1. Data protection
On May 25, 2018, the European General Data Protection Regulation (GDPR) as well as
the new German Federal Data Protection Act (Bundesdatenschutzgesetz, BDSG), and far-reaching
modifications of the data protection regulations of the 10th book of the Social Security Law (SGB) became effective [31]. The new data protection act protects registry participants towards inadmissible
processing or publishing of personal data and preserves the right of informal autonomy.
Data protection regulations are mainly determined by the possible identification of
a certain person based on transferred and stored data. The following steps of data
management are differentiated [4]:
7.1.1. Clear text storage
Medical data allowing direct conclusion on the identity of the person in clear text
may only be stored exclusively with the patients’ written consent.
7.1.2. Anonymization
Data stored in an anonymized way can no longer be decoded and thus do not allow a
direct relation to the patient. Personal data are highly protected in the context
of anonymization. An essential disadvantage of this data storage system, however,
is that data fusion from several sources or at different times (follow-ups) becomes
impossible.
7.1.3. Pseudonymization
In the context of pseudonymization, names and other identification characteristics
are replaced by a clear code (pseudonym), which impedes identification or at least
makes it difficult. Personally identifiable data are generally separated from medical
data. In contrast to anonymized storage, decoding is possible. After verification
based on data protection regulations, subsequent merging of the data is possible.
Pseudonymization, which must be consented by the patients, is often a scientifically
justified and necessary way to strike the balance between clear text storage with
open data and anonymization.
7.2. Data protection concept
All aspects regarding data protection have to be presented to the respective state
data protection commissioner in form of a data protection concept. This data protection
concept should contain the basic principles of registry development (see chapter 3)
with particular focus on the objectives, the expected benefit, patient information,
and consent. Furthermore, data on anonymization/pseudonymization and data transmission
as well as data storage and management must be displayed.
7.3. Patient information and consent
After sound information, enrolled patients have to give their written consent. This
consent is composed based on short and understandable patient information and the
declaration of the consent. Patient information should focus on the following aspects:
-
Title of the registry
-
Objective, purpose, and possible benefit of the registry
-
Duration and process of participation
-
Possible risks
-
Data on data protection and user group
-
Voluntary character of participation vs. legal obligation of reporting
-
Option of revocation
-
If applicable, remuneration/reimbursement
-
Data on legal status and responsible body
-
Contact data for possible questions
7.4. Ethical aspects
The early integration of the ethical commission for registry development is recommended.
The primary objective of the ethical commission is the consulting service for involved
physicians regarding the registry. An informal query to the responsible ethical commission
with presentation of the data protection concept and the description of the scientific
question of the registry is often sufficient. Hereby, the focus is placed on data
protection aspects in the context of collecting and assessing registry data. It is
recommended to initially apply for an ethical vote in one of the participating centers
and to include the required modifications regarding the design of the registry. The
positive vote of one center generally facilitates the decision for the ethical commissions
of other participating registry centers.
In general, for the evaluation of the ethical commission, structured application forms
are necessary that are locally different and defined by the statues of the respective
ethical commission. They always contain a synopsis of the project plan, patient information,
and an informed consent with data protection declaration. If data are assessed in
children, the people who have custody of the child receive particular information
and declarations of informed consent.
The later use of ethically perfect data fosters confidence in patients as well as
in possible sponsors and supporters of the registry.
8. Existing registries
Despite their increasing significance and growing appreciation, the knowledge about
existing registries is rather low [32]. A systematic overview about registries is currently not available. The knowledge
about closed, open, or planned registries is mainly based on incidence, personal knowledge,
publications in scientific and non-scientific journals, or online research. This lack
leads to parallel developments of projects, impedes translation of knowledge from
registries into research and healthcare provision, makes active contact of potential
study centers and subjects with registries rather difficult, and impedes the exchange
between experts of the registry operators [5]. The following registries will be described more in detail:
8.1. Cancer registry
The aim of the cancer registry is the systematic assessment and analysis of malignant
neoplasms including lymphoma and leukemia. The difference is made between epidemiological
and clinical cancer registries. Epidemiological cancer registries include the occurrence
of specific cancer diseases in a defined region. Clinical cancer registries aim at
improving cancer therapy by detailed data assessment of disease and therapy. In Germany,
the registration of cancer diseases is regulated in federal state acts with different
lengths of tradition. In 1926, the worldwide first regional cancer registry was established
in Hamburg. Since 1953, the National Cancer Registry of the German Democratic Republic
(Nationales Krebsregister der Deutschen Demokratischen Republik) exists, which continues
since 1992 as the Common Cancer Registry (Gemeinsames Krebsregister, GKR) of Berlin,
Brandenburg, Mecklenburg-Vorpommern, Sachsen, Sachsen-Anhalt, and Thuringia. The cancer
registry of the Saarland exists since 1967. With introduction of a cancer registry
in Baden-Württemberg as last federal state in Germany in 2009, the Center for Cancer
Registry Data (Zentrum für Krebsregisterdaten, ZfKD) was established at the Robert
Koch Institute ([Fig. 1]). “Cancer in Germany” (Krebs in Deutschland) appears every 2 years as common publication
of the ZfKD and the Society of Epidemiological Cancer Registries in Germany (Gesellschaft
der epidemiologischen Krebsregister in Deutschland e.V., GEKID) [33]. The most significant epidemiological parameters as well as current trends are described
for 27 different cancer entities. According to this publication, in Germany 476,120
newly diagnosed cancer patients were registered in 2014; in 2018, 493,600 are expected.
In this context, ENT specific tumors are classified into the subgroups of “Oral cavity
and pharynx” and “Larynx”. In 2014, 12,830 patients developed tumors of the oral cavity
and the pharynx (9,130 male and 3,700 female subjects) and 3,500 patients developed
laryngeal cancer (2,980 male and 520 female individuals). All tumors of the upper
aerodigestive tract show a difference regarding the incidence and the federal state
(30 tumors of the oral cavity and the pharynx per 100,000 in Mecklenburg-Vorpommern
vs. 11 per 100,000 in Hessen in males and 8 tumors of the larynx per 100,000 in Mecklenburg-Vorpommern
vs. 3.3 per 100,000 in Hessen). The reason is seen in a significantly higher consumption
of alcohol and tobacco ([Fig. 2a] and d). In female patients, tumors of the oral cavity and the pharynx have a higher relative
5-year survival rate with 59% compared to 48% in males ([Fig. 2b]). In more than 1/3 of the female patients, tumors of the oral cavity and the pharynx
are diagnosed in an early stage (T1), however, in males this rate amounts to only
one out of four ([Fig. 2c]). The relative 5-year survival rates of male laryngeal cancer patients (63%) and
females (64%) are not significantly different ([Fig. 2e]). With 44%, a higher percentage of early tumor stages (T1) at the time of diagnosis
is achieved for male patients compared to females with 37% ([Fig. 2f]).
Fig. 1 Development of the estimated comprehensiveness of epidemiological cancer registries
of the single federal states in Germany from 2002 to 2014. Quelle: Gemeinsame Publikation
des Zentrums für Krebsregisterdaten und der Gesellschaft der epidemiologischen Krebsregister
in Deutschland e.V. Krebs in Deutschland für 2013/2014. 11. Ausgabe. Robert Koch-Institut,
Berlin 2017 [rerif].
Fig. 2 Assessed, age-standardized rates of newly diagnosed diseases and mortality in the
federal states according to the gender per 100,000; categorized into tumors of the
oral cavity and pharynx a as well as tumors of the larynx d. The relative survival rate up to 10 years after first diagnosis of tumors of the
oral cavity and the pharynx is significantly higher in females than in males b; for tumors of the larynx, the difference of the relative survival rates in males
and females is not significant e. The distributions of the T stages at the time of first diagnosis are displayed in
for tumors of the oral cavity and the pharynx and in for tumors of the larynx. Quelle:
Gemeinsame Publikation des Zentrums für Krebsregisterdaten und der Gesellschaft der
epidemiologischen Krebsregister in Deutschland e.V. Krebs in Deutschland für 2013/2014.
11. Ausgabe. Robert Koch-Institut, Berlin 2017 [rerif].
Since the introduction of the Cancer Screening and Registry Act (Krebsfrüherkennungs-
und -registergesetz, KFRG) adopted in April 2013, the clinical cancer registration
in Germany is reimbursed at 90% by the statutory health insurances, the remaining
part is paid by the federal state governments. For financing of epidemiological federal
state registries, exclusively the respective federal state governments are responsible.
The Center for Cancer Registry Data of the Robert Koch Institute is paid by federal
funds.
In 1966, the single cancer registries of different nations and regions formed the
International Association of Cancer Registries (IACR) with its head office in Lyon/France [34]. In analogy to the publication on cancer in Germany [33], the World Cancer Reports of 2014 classified head and neck cancer into cancer of
the oral cavity and the pharynx as well as laryngeal cancer. In 2012, the number of
worldwide newly diagnosed cancer diseases is estimated to 529,000 for tumors of the
oral cavity and the pharynx as well as 157,000 for laryngeal carcinomas. The highest
incidence for tumors of the oral cavity and the pharynx is found in Papua New Guinea,
Bangladesh, Hungary, India, and Sri Lanka; laryngeal carcinomas are mostly found in
East Europe, Kazakhstan, and the Caribbean.
8.2. Trauma registry
The Trauma Registry of the German Society for Trauma Surgery (TraumaRegister – Deutsche
Gesellschaft für Unfallchirurgie, TR-DGU) is an association of 675 trauma hospitals
in Germany, Austria, Switzerland, and Belgium. Inclusion criterion of the TR-DGU is
the admission of patients via shock room with subsequent intensive care. The most
important parameters for the TR-DGU are the mortality, the duration of hospitalization,
and the health condition or the disability degree at the time of discharge. The objective
of the TR-DGU is to predict the survival prognosis already at the time of admission
for every patient based on the injury pattern and severity. The basic cohort of the
registry consists of more than 240,000 patients who were treated during the last 10
years (2008–2017). In 2017, 29,396 patients were registered in the TR-DGU. The mean
age amounted to 51.6 years; 70% were male and the mortality prognosis was 10.1%. Until
2017, more than 330 scientific articles have been published out of the TR-DGU that
clearly influenced the medical treatment of severely injured people. This includes
the reduced volume loading in the preclinical first-aid support, ultrasound of thorax
and abdomen (Focused Assessment with Sonography for Trauma, FAST), the introduction
of whole-body computed tomography in the shock room, the standardized training concept
(Advanced Trauma Life Support, ATLS) as well as the early treatment of injury-related
coagulation disorders [35].
8.3. Stroke registry
The Workgroup of German Stroke Registries (Arbeitsgemeinschaft Deutschsprachiger Schlaganfall-Register,
ADSR) is a consortium of the regional stroke registries of Baden-Württemberg, Bavaria,
Berlin, Erlangen, Hamburg, Hessen, Nordrhein, Northwestern Germany, Rheinland-Pfalz,
and Schleswig-Holstein for the assessment of standardized data on stroke. An association
of the single registries to one large stroke registry has not been realized up to
now [36].
8.4. Medical technology registry
In the field of medical technology, 101 registries are found in Europe. The sections
of cardiology (heart pacemaker and coronary stents) (n=38), arthroplasty (n=29), and
breast implants (n=9) are the leading ones [37].
For cochlea implants, only the Swiss Cochlea Implant Registry exists in Europe. It
was founded in 1992 by five Swiss CI centers and since 1977 it comprises 3,096 implantations
([Table 1]) [38]. Audiological speech test conditions for children (monosyllable, trochee, polysyllable
[MTP] test) as well as for adolescents and adults (Freiburg monosyllable test) were
defined in a common workgroup of the five CI hospitals in Switzerland. 67% of the
children reached discriminations between 80 and 100% in the MTP test; more than half
of the adult CI patients had a word understanding of more than 50%.
|
0–3 Jahre
|
3–12 Jahre
|
12–18 Jahre
|
18–65 Jahre
|
>65 Jahre
|
|
|
Gesamt
|
534
|
675
|
201
|
1282
|
404
|
3096
|
|
bilateral
|
183
|
183
|
43
|
206
|
25
|
640
|
8.5. Newborn hearing screening
The universal newborn hearing screening was introduced nationwide in 2009; since September
2016 it is part of the directive for children (Kinderrichtlinie, §§ 47–57) [39]. The final report on the evaluation of the newborn hearing screening of 2011/2012
dated January 15, 2017, showed that in 2012 a newborn hearing screening could be documented
in 82.4% (554,578) of the children. Significant differences between the single federal
states could be observed. While in Baden-Württemberg 42.8% and Niedersachsen 37.9%
of the newborns were not examined, the percentage of non-examined newborns amounted
to 0.2% in Mecklenburg-Vorpommern and to 0.7% in Sachsen-Anhalt. In 3.7% of the children
with conspicuous screening result, a hearing disorder was diagnosed; in 56.2% hearing
disorder could be excluded, and in 40.1% no final result was documented (“lost to
follow-up”). The prevalence of a bilateral, permanent, congenital hearing disorder
was estimated to 1.3:1,000 newborns based on present data. Up to 7% of the children
with diagnosed hearing disorder had an inconspicuous screening. In 2012, the sensitivity
amounted to 95.1%, the specificity to 97.1%, and the positive-predictive value to
6.2% [40].
8.6. Registry of orphan diseases
Most registries exist for orphan diseases, since clinical trials are rather difficult
to conduct. Currently, there are 846 registries of different quality with various
objectives and concepts [41].
8.7. EudraCT – Registry for clinical trials
EudraCT (European Union Drug Regulatory Authorities Clinical Trials) is a registry
for clinical drug studies conducted in the European Union. It exists since 2004. EudraCT
is operated by the European Drug Agency and used for approval and monitoring of clinical
trials by the drug authorities of the member states.
The EudraCT registry was established to increase the transparency of clinical trials
conducted in the EU and to improve the security for study participants by better monitoring.
The legal basis for its structure is article 11 of the directive 2001/20/EG for application
of good clinical practice (GCP). GCP defines for Germany that the approval may only
be applied for when a planned clinical trial has been registered in EudraCT. The registry
is active since May 1, 2004, and as of October 2018 more than 55,355 trials have been
registered [42].
9. Outlook
The application and utilization possibilities of registries are manifold. Physicians
in hospitals, private practices, and research, scientists, and medical associations
use registries as basis for preventive measures, clinical questions, quality management,
healthcare research, and politics. Up to now, oto-rhino-laryngology is not significantly
involved in the work of registries. This is reflected by the fact that the DGHNO is
the only medical professional society that is not member of the DNVF. The membership
and active participation of the DGHNO in the DNVF is an objective that should be pursued
as soon as possible.
In Germany, the section of ENT specific oncology is sufficiently represented by the
cancer registry. The systematic registration of the newborn hearing screening is currently
further developed. A drastic reduction of the non-examined newborns in all federal
states as well as the improved quality of data assessment is necessary to avoid that
newborns with relevant hearing disorder are not identified.
The white paper on cochlea implantation [43] that has been established by the presidency of the DGHNO in April 2018 contains
recommendations on the structure, organization, equipment, qualification, and quality
management in the treatment of patients with CI in Germany. The treatment of patients
with high-grade congenital or acquired hearing impairment or deafness is a complex
process that is only successful with the support of audiological, pedagogical, technical,
and medical expertise within a cochlea implanting institution. The process of CI includes
the preoperative care and consultation, implantation, postoperative basic and consecutive
therapy as well as life-long follow-up. Failures in the CI treating process lead to
missing or insufficient hearing and speech development of affected children, an insufficient
quality of the outcome, reduction of the quality of life, loss or lacking recovery
of socialization and ability to work as well as medical complications. The white paper
on cochlea implantation is meant to be a future basis for certification of cochlea
implanting institutions as well as the foundation of a national CI registry. The data
collection of the CI registry is subdivided into the following 9 data blocks.
-
Basic data (treating institution, patient ID, pseudonym, date of birth, gender, mother
language)
-
Preoperative audiometry (audiogram [500, 1000, 2000, 4000 Hz]; Freiburg test for numbers;
Freiburg test for monosyllables [65, 80, 100 dB SPL])
-
Preoperative hearing history (hearing loss since birth, childhood, adolescence, adulthood,
hearing loss/deafness in years [0–1, 1–5, 5–10, 10–20,>20]; use of hearing aids with
CI)
-
Implantation (date of implantation; implant manufacturer; serial number)
-
Surgery (date of surgery; primary/revision surgery; electrode insertion [round window,
cochleostomy]; insertion depth [partial, complete]; radiological control [conventional
X-ray Stenvers, CBT, CT scan])
-
CI-related complications (malposition of the electrode requiring revision; facial
paresis; inpatient admission; meningitis; death)
-
Use of CI and progress of rehabilitation (patient presented for follow-up; duration
of CI use [in hours per day] based on patient’s report/data logging; current rehabilitation
status [basic therapy, consecutive therapy, follow-up])
-
Postoperative audiometry (time after CI in months; audiogram without CI; use of acoustic
components/EAS; contralateral side in cases of residual hearing occluded/masked; Freiburg
monosyllables test with CI at 65 dB SPL; sentence tests [OlSa, GöSa, HSM] in silence
or in noise)
-
Quality of life (modified/translated “Nijmegen Cochlear Implant Questionnaire” [NCIQ])
Due to the assessment of multiple parameters in nearly all aspects of the discipline,
otorhinolaryngology presents excellent preconditions for implementation of registries.
Completeness, comprehensiveness, and high data validity significantly determine the
quality of registries. The basis is the positive vote and acceptance of the registry
by patients as well as reporting institutions. This has to be taken into consideration
when planning and developing registries. In otology, numerous subjective and objective
audiological test procedures exist. If test parameters were standardized, e. g. the
conduction of the Freiburg speech understanding at 65 and 80 dB, the implementation
of registries for the topics of “chronic otitis media”, “active middle ear implants”,
“sudden hearing loss”, or “vestibular schwannoma” could be imagined. Also the systematic
registration of vertigo with vestibular genesis, allergology, rhinology, and phoniatrics
are a basis for prevention and therapy. Especially those established, standardized,
and entirely digitally and metrically stored measurements allow the creation of registries
in a unique way ([Fig. 3]).
Fig. 3 Possibilities of implementation of registries in the discipline of otorhinolaryngology.
With the historic background and the long tradition of our discipline with all its
manifold therapeutic procedures that are partly applied since long time and often
even in an unmodified way, the scientific evidence-based confirmation and verification
by means of registries is an unparalleled chance for the further development of otorhinolaryngology.
