BioMed Central
BMC Medical Research 
MethodologyBMC Medical Research Methodology 2001, 1Research article
Quality control and data-handling in multicentre studies: the case of 
the Multicentre Project for Tuberculosis Research
Teresa Caloto1, Consuelo Huerta1, Teresa Moreno1, Dolores Guerra1, 
José Alcaide2, Concha Castells3, José I Cardenal4, Angela Domínguez2, 
Pilar Gayoso5, Gonzalo Gutiérrez6, Maria J López7, Francisco Muñoz8, 
Carmen Navarro9, Miguel Picó10, Francisco Pozo1, José R Quirós11, 
Francisco Robles12, José M Sánchez13, Hermelinda Vanaclocha14, 
Tomás Vega15 and Mercedes Diez*1 for the MPTR Study Group
Address: 1Unidad de Investigación en Tuberculosis, Instituto de Salud Carlos III, Sinesio Delgado, 6, 28029 Madrid, Spain;, 2Departamento de 
Sanidad y Seguridad Social, Dirección General de Salud Pública, Travessera de les Corts 131-159, 08028 Barcelona Spain;, 3Departamento de 
Sanidad, Delegación Territorial, María Díaz de Haro 60, 48010 Bilbao Spain;, 4Consejería de Bienestar Social, Servicio Territorial, Plaza de 
Alféreces Provisionales s/n, 10071 Caceres, Spain;, 5Complejo Hospitalario Cristal-Piñor, Ramón Puga 54, 32005 Orense, Spain;, 6Dirección 
General de Salud Pública, Avenida de Francia 4, 45071 Toledo, Spain;, 7Consejería de Salud Consumo y Bienestar Social, Dirección General de 
Salud y Consumo, Villamediana 17, 26071 Logroño, Spain;, 8Hospital Universitario de Valme, Carretera de Cádiz s/n, 41014 Sevilla, Spain;, 
9Consejería de Sanidad y Política Social, Dirección General de Salud, Ronda de Levante 11, 30008 Murcia, Spain;, 10Dirección General de Salud 
Pública, Avenida de la Innovación s/n, Edificio Arena 1, 41020 Sevilla, Spain;, 11Dirección Regional de Salud Pública, General Elorza 32, 33001 
Oviedo, Spain;, 12Dirección Provincial de Sanidad de Melilla, Plaza 1 de Mayo s/n, 29803 Melilla, Spain;, 13Dirección Provincial de Sanidad de 
Ceuta, Carretera San Amaro 12, 51001 Ceuta, Spain;, 14Dirección General de Salud Pública, Doctor Rodríguez Fornos 4, 46010 Valencia, Spain; 
and 15Dirección General de Salud Pública y Asistencia, Avenida de Burgos 5, 47071 Valladolid, Spain
E-mail: Teresa Caloto - Teresa_caloto@merck.com; Consuelo Huerta - chuerta@ceife.es; Teresa Moreno - mmoreno@isciii.es; 
Dolores Guerra - lola@enterprise.eui.upm.es; José Alcaide - jalcaide@dsss.scs.es; Concha Castells - depidebi-san@eg-gv.es; 
José I Cardenal - jicardenal@bme.es; Angela Domínguez - angelad@dsss.scs.es; Pilar Gayoso - pgayoso@cristalp.es; 
Gonzalo Gutiérrez - ve@jccm.es; Maria J López - mjose.lopez@larioja.org; Francisco Muñoz - med000552@nacom.es; 
Carmen Navarro - Carmen.Navarro@carm.es; Miguel Picó - sito@arrakis.es; Francisco Pozo - fpozo@h120.es; 
José R Quirós - ramonqg@princast.es; Francisco Robles - froblesf@camelilla.es; José M Sánchez - sanfer@teleline.es; 
Hermelinda Vanaclocha - vanaclocha_her@gva.es; Tomás Vega - sybs.epi@dvnet.es; Mercedes Diez* - mdiez@isciii.es
*Corresponding author
Abstract
Background: The Multicentre Project for Tuberculosis Research (MPTR) was a clinical-
epidemiological study on tuberculosis carried out in Spain from 1996 to 1998. In total, 96 centres
scattered all over the country participated in the project, 19935 "possible cases" of tuberculosis
were examined and 10053 finally included. Data-handling and quality control procedures
implemented in the MPTR are described.
Methods: The study was divided in three phases: 1) preliminary phase, 2) field work 3) final phase.
Quality control procedures during the three phases are described. Results: Preliminary phase: a)
organisation of the research team; b) design of epidemiological tools; training of researchers. Field
work: a) data collection; b) data computerisation; c) data transmission; d) data cleaning; e) quality
control audits; f) confidentiality. Final phase: a) final data cleaning; b) final analysis.
Conclusion: The undertaking of a multicentre project implies the need to work with a
heterogeneous research team and yet at the same time attain a common goal by following a
homogeneous methodology. This demands an additional effort on quality control.
Published: 21 December 2001
BMC Medical Research Methodology 2001, 1:14
Received: 9 October 2001
Accepted: 21 December 2001
This article is available from: http://www.biomedcentral.com/1471-2288/1/14
© 2001 Caloto et al; licensee BioMed Central Ltd. Verbatim copying and redistribution of this article are permitted in any medium for any purpose, 
provided this notice is preserved along with the article's original URL.Page 1 of 6
(page number not for citation purposes)
BMC Medical Research Methodology 2001, 1 http://www.biomedcentral.com/1471-2288/1/14Background
Multicentre studies call for additional logistic and meth-
odological effort, yet this is offset by the advantages to be
gained from obtaining a larger sample more quickly and
improving the external validity of the results.
The Multicentre Project for Tuberculosis Research (MPTR)
was a clinical-epidemiological study conducted into tu-
berculosis (TB) in Spain during the period, 1996–1998.
For the purposes of the study a TB case was defined as an-
yone who fulfilled the following two conditions: a) mi-
croscopy and/or culture positive for Mycobacterium
tuberculosis complex ; and, b) therapy with at least two anti-
TB drugs prescribed by a physician. Subjects who met the
second but not the first condition were only included as
cases if the prescription was still in place after three
months. The field work in the MPTR comprised: a) iden-
tifying 19935 TB suspects by a monthly search of 14 data-
bases for one year: an specific definition of TB suspect was
established for each database; b) reviewing the respective
clinical histories; and, c) collecting and computerising de-
tailed information on the 10053 cases that met the case
definition. These tasks were undertaken at a local level in
all of the 96 participant public health areas (PHA), situat-
ed in 13 of Spain s Autonomous Regions (AR), namely,
Andalusia, Principality of Asturias, Castile-La Mancha,
Castile & Leon, Catalonia, Extremadura, Galicia, La Rioja,
Murcia, Basque Country, Valencia, Ceuta and Melilla.
Data were first aggregated at a regional level, and thereaf-
ter at the Tuberculosis Research Unit of the Carlos III In-
stitute of Public Health, which acted as the Co-ordinating
Centre (CC) and performed the necessary data-analysis.
Several papers have been published based on the results
from the MPTR [1–3].
Methods
The study was divided into three phases, each one subdi-
vided into different processes which are summed up in
the following:
1) preliminary phase: organisation of the research team,
design of epidemiological tools and training of research-
ers,
2) field work: data collection, data-computerisation and -
transmission, data cleaning, quality control audits and
confidentiality, and
3) final phase: data cleaning and final analysis.
The type of action taken at each phase of the process to en-
sure the reproducibility and validity of the information,
along with the procedures implemented in order to meas-
ure quality (Figure 1), are described below.
Results
Preliminary phase
Data quality control is an aspect that has to be considered
at the planning phase of any study, and particularly so in
cases, such as multicentre studies, which necessarily in-
volve researchers based at facilities that are far apart.
Organisation of the research team
The MPTR was structured as a co-ordinated project having
the above three levels of action, i.e., PHA, AR and CC, with
specific tasks allocated to each. To monitor the validity of
the results and resolve logistic or methodological prob-
lems, a Project Management Team (Equipo Directivo del
Proyecto) was formed, made up of CC personnel and rep-
resentatives from each of the Autonomous Regions. The
Team met five times during this phase to decide method-
ological and organisational aspects. Teams with similar
responsibilities were set up at both regional and local lev-
els.
Design of epidemiological tools
In order to standardise data collection on the 124 study
variables, a structured questionnaire was designed and a
detailed handbook drawn up, containing definitions for
each variable.
Two books were designed, namely, the Status Report (Es-
tadillo) and "Log Book" (Libro de Registro). Whereas the
former recorded the progress of the TB suspects from de-
tection until confirmation, the latter systematically reflect-
ed the date, the name of the person doing the screening,
the study procedures followed and any incidents arising at
participant health-care facilities, AR and the CC.
A data-computerisation software application was pur-
pose-designed, which in addition to all the standard func-
tions, allowed for: a) data validation and monthly review
of data consistency; b) detection and deletion of all dupli-
cate entries; c) a breakdown of all cases pending informa-
tion or confirmation; d) generation of random samples
designed to check for data-entry errors; e) on-line person-
al data encryption.
Similarly, a second computer programme was specifically
developed to detect inconsistencies, with all data being
duly screened before onward transmission to higher lev-
els.
Training of researchers
All research staff tasked with case searching and data col-
lection attended a two-day course, imparted in each AR by
the same person.Page 2 of 6
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BMC Medical Research Methodology 2001, 1 http://www.biomedcentral.com/1471-2288/1/14Figure 1
Data flow and procedures for quality control. MPTRPage 3 of 6
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BMC Medical Research Methodology 2001, 1 http://www.biomedcentral.com/1471-2288/1/14Field work
Data collection
The searching of the 14 databases used to identify TB sus-
pectsand reviewing of the clinical histories were both car-
ried out in strict accordance with the study protocol.
Under its terms, "TB suspects" were to be identified by
means of a monthly search of all databases and duly re-
corded in the Status Report. The clinical histories of all
such TB suspects were then reviewed: where the case was
confirmed, the relevant information was recorded in the
questionnaire and subsequently computerised; and where
the TB suspect was not confirmed, a note of the reason for
no confirmation (disease different from TB, out of the
study period etc.) was entered into the Status Report, so
that in each instance a judgement could be made on the
appropriateness of not confirming the case.
Data-computerisation and -transmission
Data were computerised and sent monthly from PHA to
the AR. Here, after undergoing aggregation and quality
control, these same data were dispatched within 10 days
to the Tuberculosis Research Unit, where they were fed
into the central database. Copies of all such databases and
questionnaires remained at the various PHA and AR for
the duration of the study. When the study had been con-
cluded, all materials used (Log Books, Status Reports and
questionnaires) were sent to the Tuberculosis Research
Unit for filing, along with a final report confirming that
the work had been done as per instructions.
To ensure data-entry quality, the Tuberculosis Research
Unit typed in duplicate data for a random sample of 926
entries (approximately 10% of cases). There was an aver-
age of 15.3 errors per 10,000 characters, an error rate
which is smaller than those of 22/10,000 and 23/10,000
found in studies where data-entry was performed locally
as in the MPTR [4,5], but higher than the error rate of 9.5/
10,000 or 3.8/10,000 found in studies were data entry was
performed centrally [6,7].
Data cleaning
All information forwarded by the AR underwent a month-
ly check for duplicates and errors at the Tuberculosis Re-
search Unit, with any resulting flaws or discrepancies
being recorded on monthly quality-control reports that
were sent to the respective AR. In any instance where it be-
came necessary for information to be checked and errors
corrected, the AR instructed the pertinent PHA to carry out
a new review of the relevant questionnaires or clinical his-
tories; this continued procedure for quality control al-
lowed for differences in quality of data collection between
the 96 centres to be corrected by the end of the study. A
record was kept of all amendments made. Quarterly anal-
yses were run on the overall database to check for biases
in data collection.
Quality control audits
The head researcher at each participant health-care facility
inspected the Logbooks and Status Reportsonce a month,
to check whether the facts on record indeed corresponded
to the procedures carried out. Moreover, to verify whether
the information had been recorded accurately, a duplicate
collection of data was made on the basis of the clinical
histories of 5% of cases selected at random (520 cases
overall).
Head researchers in the AR visited all the participant
health-care facilities in the region once at the commence-
ment, once at the end, and at quarterly intervals through-
out the study. At three-monthly intervals, Tuberculosis
Research Unit staff carried out an audit at a randomly se-
lected facility in each of the AR. To standardise the audit-
ing process and forestall omissions and oversights, the
same quality control questionnaire was used for all visits,
with detailed attention to all aspects to be monitored.
The results of these audits were recorded in the relevant
Logbooks and ad hoc reports issued by the auditors to the
Project Management Team. These reports were then dis-
cussed at the quarterly meetings, along with the partial
analyses and any other items of interest.
Confidentiality
In line with Spanish law governing data-protection, the
following measures were adopted:
a) database access was restricted, with each PHA allocated
an installation code, as well as an access code subject to
change every three months;
b) questionnaires and diskettes were stored under lock
and key; and,
c) all identification data in the database were encrypted,
and all such data in copies of questionnaires forwarded to
AR and CC, deleted. In data sent via courier (with tele-
phonic notification of dispatch and receipt), patients were
solely identified by an eleven-digit code.
Data cleaning and final analysis
On conclusion of the study, the CC unified the informa-
tion proceeding from the three study levels by comparing
the respective databases, carrying out the pertinent correc-
tions and eliminating all duplicates. Each Region was fur-
nished with a copy of its own final database.
For the purposes of analysis of tuberculosis incidence: cas-
es were assigned to their respective health districts; va-
grants were included in their Autonomous Region of
residence; and patients who resided outside of the study
area, were excluded.Page 4 of 6
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BMC Medical Research Methodology 2001, 1 http://www.biomedcentral.com/1471-2288/1/14Discussion
Except in the case of clinical trials, published papers do
not generally go far enough in providing the kind of de-
tailed description demanded by quality-control method-
ology [8]. However, this is a matter of great practical
importance that should be borne in mind in all phases of
developing any project, and even more so in the case of a
multicentre project.
The period preceding data collection is fundamental. It is
in this phase that the organisation of the study has to be
decided, data-collection procedures established, epidemi-
ological tools designed, and data-collection and -compu-
terisation personnel trained. It is therefore essential that
sufficient time be devoted to the task, so as to ensure that
no fieldwork begins until the procedures have been well
defined, the epidemiological tools have been validated
and distributed, and the researchers have received all the
necessary training [6,9]. In line with the designated study
objectives, this is the time to determine the precise nature
of the information required and the manner of collecting
same, without losing sight of the fact that the amount of
data collected will inevitably exert a direct influence on
the time employed and the end quality of the information
[10].
The functions, both of the researchers and the various
bodies involved, must be perfectly defined and delimited
in the preliminary phases of the project, since it is upon
these that the overall quality of the study will depend
[9,11]. In the MPTR, three organisational levels with spe-
cific tasks and well-defined channels of communication
were demarcated. We feel that herein lies one of the keys
to the project s success, given that the execution of a uni-
form study in 96 widely dispersed health areas would be
simply impossible unless all the parties involved have a
clear idea as to what their responsibility is and to whom
they are answerable when problems arise.
In the context of multicentre studies, special mention
should be made of the CC, whose role in this type of
project is crucial [12]. There is unanimity as regards en-
trusting the CC with the mission of ensuring the validity
of the results, and it is this body that must thus take charge
of organising and training researchers, implementing
quality control and undertaking data handling and -anal-
ysis. In order to be able to perform these functions, mech-
anisms for co-ordination and feedback between the CC
and the various organisational levels must be set up
[9,13,14].
An important aspect is to ascertain whether data compu-
terisation is to be delegated to the participating centres or
carried out by the CC [15]. The decision must be taken on
the basis of the amount of information, the time availa-
ble, the geographical spread of the centres and the re-
sources available. Although this task tends to be
centralised in the majority of studies, performing it locally
is swifter, provides researchers with direct knowledge of
their data without having to depend upon the informa-
tion supplied by the CC and, by extension, enhances their
involvement in the study. In contrast, the participation of
a great number of individuals in this process calls for qual-
ity control to be tightened in respect of data entry [9].
When training researchers, it must be remembered that
quality control can make no sense if those tasked with
computerising the data fail to understand the importance
of their work and so develop no commitment to it. It is at
this point therefore that the objectives of the study must
be described in detail, stress laid on the importance of
having reproducible and high-quality information as a
means of attaining said goals, and the implications of in-
complete or low quality data discussed.
Opinions differ as to the real need for double data entry
and the level at which this should be done. Some authors
consider that the improvements in data quality do not jus-
tify the extra time and cost involved [16–19], given that in
such cases all the study procedures must be doubled [16].
Others feel, however, that double data entry is justified be-
cause it has been used in numerous studies and serves to
assure quality [4,6,20]. Finally, there are those that pro-
pose alternatives to this practice. In the MPTR, data entry
control was deemed necessary in a sample of sufficient
size to ensure that the results obtained were in line with
what was judged acceptable [4–7].
The need to carry out regular audits of participant facilities
in multicentre studies has been highlighted by bodies
such as the National Cancer Institute (USA), which not
only requires facilities to draw up a programmed audit
schedule but has also published audit performance guide-
lines for the purpose [8]. Where researchers know that
their work is going to be reviewed and assessed, they exer-
cise greater care in the process of gathering the informa-
tion, leading in turn to enhanced reliability of results.
Periodically, project status reports should be issued and
circulated to the researchers.
Conclusions
In conclusion, it has to be said that the undertaking of a
multicentre project implies the need to work with a heter-
ogeneous and widely dispersed study population and re-
search team, and yet at the same time attain a common
goal by following a homogeneous methodology. This de-
mands an additional effort in collecting the data: on the
one hand, in order to unify methods and implement
measures that minimise the variability injected by the
high numbers of individuals participating in the process;Page 5 of 6
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BMC Medical Research Methodology 2001, 1 http://www.biomedcentral.com/1471-2288/1/14and, on the other hand, to establish mechanisms that
monitor and measure the quality of the data collected.
While both aspects are essential to ensure the validity of
the results and therefore important to any study, there can
be no doubt that they have to be that much more com-
plete and comprehensive in multicentre studies. The
MPTR is the largest TB study ever undertaken in Spain,
and has yielded extremely valuable information on the
disease [1–3]. We believe that this was possible due to the
rigour with which the quality control mechanisms were
implemented over the course of the study and served to
enable highly reproducible and valid results to be ob-
tained.
Members of the Study Group
listed in  [ http://www.isciii.es/unidad/sgecnsp/centros/
cne/infgralcne.html] 
Acknowledgements
This work was funded by a FIS grant, Exp. 99/0016. Dolores Guerra was 
funded with 2 grants by the Instituto de Salud Carlos III (96/4186 y 97/
4040).
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