STUDY PROTOCOL Open Access
The UP-TECH project, an intervention to support
caregivers of Alzheimer’s disease patients in Italy:
study protocol for a randomized controlled trial
Carlos Chiatti*, Filippo Masera, Joseph M Rimland, Antonio Cherubini, Osvaldo Scarpino, Liana Spazzafumo,
Fabrizia Lattanzio on behalf of the UP-TECH research group
Background: The epidemic of Alzheimer's disease (AD) represents a significant challenge for the health care and
social service systems of many developed countries. AD affects both patients and family caregivers, on whom the
main burden of care falls, putting them at higher risk of stress, anxiety, mortality and lower quality of life. Evidence
remains controversial concerning the effectiveness of providing support to caregivers of AD patients, through case
management, counseling, training, technological devices and the integration of existing care services. The main
objectives of the UP-TECH project are: 1) to reduce the care burden of family caregivers of AD patients; and 2) to
maintain AD patients at home.
Methods/design: A total of 450 dyads comprising AD patients and their caregivers in five health districts of the
Marche region, Italy, will be randomized into three study arms. Participants in the first study arm will receive
comprehensive care and support from a case manager (an ad hoc trained social worker) (UP group). Subjects in the
second study arm will be similarly supported by a case manager, but in addition will receive a technological toolkit
(UP-TECH group). Participants in the control arm will only receive brochures regarding available services. All subjects
will be visited at home by a trained nurse who will assess them using a standardized questionnaire at enrollment
(M0), 6 months (M6) and 12 months (M12). Follow-up telephone interviews are scheduled at 24 months (M24). The
primary outcomes are: 1) caregiver burden, measured using the Caregiver Burden Inventory (CBI); and 2) the actual
number of days spent at home during the study period, defined as the number of days free from
institutionalizations, hospitalizations and stays in an observation unit of an emergency room.
Discussion: The UP-TECH project protocol integrates previous evidence on the effectiveness of strategies in
dementia care, that is, the use of case management, new technologies, nurse home visits and efforts toward the
integration of existing services in an ambitious holistic design. The analysis of different interventions is expected to
provide sound evidence of the effectiveness and cost of programs supporting AD patients in the community.
Trial registration: ClinicalTrials.gov: NCT01700556
Keywords: Alzheimer’s disease, Technology, Caregiver burden, Quality of life, Integrated care, RCT, Italy
The World Alzheimer Report estimated that there were
35.6 million people living with dementia worldwide in
2010, and according to forecasts this figure will reach 65.7
million by 2030 and 115.4 million by 2050 . The Italian
National Institute of Statistics (Istat) estimated that there
were approximately250,000people sufferingfrom
Alzheimer’s disease (AD) and similar dementias in Italy in
2005 . However, since AD and various forms of age-
related cognitive deterioration have complex diagnoses,
their prevalence is likely to be underestimated [3,4].
AD causes progressive cognitive and functional decline
, it can have a significant impact on care costs, and is
the major cause of nursing home admission . To accur-
ately estimate the societal impact of AD, one needs to
consider that patients' families are also affected, since the
* Correspondence: firstname.lastname@example.org
Italian National Research Center on Aging (INRCA), Ancona, Italy
© 2013 Chiatti et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Chiatti et al. Trials 2013, 14:155
burden of care in many countries, including Italy, mainly
falls on them. AD is known as a ‘family illness’, because
family caregivers of AD patients often represent hidden
secondary patients . They frequently experience high
levels of stress, associated with a higher risk of developing
mood disorders, depression, insomnia and a lower quality
of life . Anxiety and stress also increase their likelihood
of developing physical problems, such as headache, back
pain and excess weight, and exposes them to a higher rate
of mortality compared to their non-caregiver counterparts
Despite controversies , promising intervention stud-
ies have shown that specific interventions aimed at
supporting caregivers of AD patients can lead to signifi-
cant improvements in their physical and mental health, by
reducing caregiver burden and stress . For instance,
caregivers receiving specific counseling sessions provided
care for longer and delayed the institutionalization of their
relatives with AD [13-17]. Counseling of family members
delayed admission of the patient to a long-stay facility for
an average of 18 months . An experimental program
of intensive training, followed by 10 days of follow-up
contacts, delayed the institutionalization and reduced the
level of caregiver stress [13,18]. In the USA, telephone-
based psychosocial support was effective at lowering care-
giver stress , suggesting that such interventions can
provide an interesting low-cost solution to support
In this context, new technologies applied to the home
hold great potential to improve the quality of life of AD
patients and their caregivers. Despite the absence of de-
finitive evidence , pilot studies revealed that home ad-
aptations designed to assist older people in fulfilling their
daily needs in the home are particularly important for
users' quality of life and well-being . Several studies
assessing the effectiveness of assistive technology in AD
have been undertaken; however, most of these inter-
ventions are in a prototype/testing phase and fail to be
scaled-up and systematically implemented in daily prac-
tice. A few of these include: talking lights, the Home As-
surance System project , the ROSETTA project 
and the ENABLE project . The latter project involved
the testing of an integrated system of technologies in the
home, including automatic night lights, locators for
lost objects, computerized calendars, programmable tele-
phones, gas sensors, touch screen pads for music and a
voice prompter when medicines should be taken.
One of the largest intervention studies undertaken in
the field is the Resources for Enhancing Alzheimer's Care-
giver Health (REACH) project, which was launched in the
USA in 1995 . Sponsored by the National Institute on
Aging and the National Institute of Nursing Research, the
main objective was to develop a psychosocial intervention
to improve the living conditions of caregivers of AD
patients. The REACH project implemented a multi-
component intervention, including: 1) individual support
of caregivers; 2) group support and family therapy; 3)
training of caregivers; 4) interventions to adapt to the
home; and 5) the use of technology support systems
(for example a telephone-linked computer system and a
computer telephone integration system). Evidence sug-
gests that the program was effective at both improving
caregivers' quality of life and in delaying the insti-
tutionalization of AD patients [8,26], and even today this
multi-site intervention represents a major testbed for
evidence-based evaluation of practices in the field of de-
An important issue to consider when implementing
programs to improve care pathways for AD patients is
that the care of these patients is an extremely complex
process. Public welfare professionals must take into ac-
count multiple care needs (for example health, social and
legal), without neglecting the importance of the caregiver
and their needs as well. The multidimensionality of this
problem not only calls for new services, but also for a
greater coordination and integration of existing commu-
nity health care and social services, within the public,
non-profit and private sectors. This was the assumption
underlying several projects integrating health care and so-
cial services, thus reducing cost, and eliminating waste
and inefficiency [27-30]; however, none of these specific-
ally addressed AD patients and their caregivers. Among
the tools used in these studies to foster integration of care
are case management strategies, staff training and the use
of new information technology (IT) systems.
The Italian welfare system has traditionally relied on a
family-based approach to older people care. Here, the
level of formal care provision has always been marginal
when compared to other Western welfare systems, such
as those of the UK, Germany and Scandinavian countries
. However, stimulated by the increasing dimension of
AD and its consequences on families, the Italian Ministry
of Social Welfare decided to invest in the innovation of
care services in this field. A call for proposals was issued
in 2010 addressing public service providers, with the aim
of developing innovative interventions, and improving the
effectiveness of care for AD patients and their caregivers
in the Italian regions.
Responding to this call and building on the knowledge
retrieved in the literature, the Italian National Research
Centre on Aging (INRCA) in partnership with the Gov-
ernment of the Marche region, developed the proposal of
the UP-TECH intervention study, which was successfully
evaluated and funded with a grant of approximately 1 mil-
lion euros. The ambitious idea underlying this project is
to create a multi-component intervention program at re-
gional level, which could engage professionals working in
both the social and health care services, in a large-scale
Chiatti et al. Trials 2013, 14:155
Page 2 of 11
organizational change to restructure the processes of AD
care. For these reasons, a study has been designed follow-
ing the trial methodology and adapting to the Marche re-
gion the most promising evidence-based interventions in
The main project objectives of the UP-TECH study
are: 1) to reduce the care burden of family caregivers of
AD patients; and 2) to maintain AD patients at home.
Secondary objectives of the project are: 1) to ensure
continuity of care and the integration of care pathways; 2)
to create an information management system specific
for AD; and 3) to evaluate the cost-effectiveness of a
case management program for AD patients and their
UP-TECH is a multi-component, randomized, controlled
trial, lasting 12 months, and enrolling dyads composed of
an AD patient and their primary family caregiver. A total
of 450 dyads, living in five different health districts of the
Italian Marche region, will be randomized into three
arms: 1) 150 dyads provided with systematic and com-
prehensive support of a trained social worker acting as
case manager and receiving three nurse home visits
(UP group); 2) 150 dyads provided with systematic and
comprehensive support of a trained social worker acting
as case manager, receiving an assistive technology inter-
vention and three nurse home visits (UP-TECH group);
and 3) 150 dyads receiving ‘light’ support in the form of a
paper brochure and three nurse home visits (control
AD patients are subjects with a pre-existing diagnosis of
AD, in an intermediate stage, according to the 2011 cri-
teria of the National Institute on Aging-Alzheimer's Asso-
ciation (NIA-AA) [32-34], with a mini-mental state
examination (MMSE) score  between 10 and 20, living
in the community, and assisted by at least one family
Family caregivers are defined as those kin either living
or not living with the patient (if not habitually living
with the patient, then living in the same municipality),
who care for and directly support the patient with the
activities of daily living (ADL) and instrumental activities
of daily living (IADL) for at least 1 hour per day within
the last 6 months. Where there is more than one family
caregiver, the primary caregiver, that is, the family mem-
ber who spends more hours assisting the patient, will be
included in the trial.
The exclusion criteria are: 1) lack of informed consent
from the AD patient or caregiver. If the patient has
been declared legally incompetent or has a support
administrator appointed, informed consent will be re-
quested from a family member or from a person
appointed by a judge. In the case of natural incapacitation,
verified by Alzheimer Evaluation Unit (AEU) doctors, con-
sent for the patient will be requested from the primary
caregiver; 2) presence of severe diseases associated with
disability in ADLs, life expectancy less than 6 months in
addition to AD, or unstable chronic conditions in both the
AD patient and the family caregiver, as assessed by the
AEU and other professionals in the health district; 3)
intention of moving out of the health district within 12
months; 4) enrolled in another experimental trial; and 5)
lack of a family caregiver or a caregiver less than 18 years
Outcomes of the study
The main outcomes of the study are: 1) caregiver burden,
measured using the Caregiver Burden Inventory (CBI)
multi-dimensional questionnaire, administered by a trained
nurse. The CBI has five subscales: time-dependence bur-
den, developmental burden, physical burden, social burden
and emotional burden, and includes a set of 24 items eval-
uated using a 5-point Likert scale ranging from 0 (not at
all) to 4 (very much), which are summed. A total score
higher than 36 indicates a risk of stress, whereas scores
near or slightly above 24 indicate a need to seek some form
of respite care . During the study, the Italian version of
the CBI validated by Marvardi and colleagues will be used
; and 2) the actual number of days spent at home by
the AD patient during the observation period, defined as
days free from episodes of institutionalizations, inpatient
hospitalizations and brief stays in an observation unit of an
emergency room. This outcome will be treated as a con-
tinuous variable and will be calculated at each assessment
(6 months, M6; 12 months, M12; and 24 months, M24) by
subtracting from the total days of observation, the number
of days of institutionalization in an assisted residence
facility, care home and/or nursing home inpatient, hos-
pitalizations, and brief stays in an observation unit of an
In addition, the following outcomes will be evaluated at
the end of the trial: 1) quality of life of the caregiver of the
AD patient, measured using the Italian validated version
of the quality of life questionnaire, SF-12 [38,39]; 2) anx-
iety and depression of caregivers, measured using the
Italian validated version of the Hospital Anxiety and De-
pression Scale (HADS) [40,41]. HADS is a 14-item scale,
seven of the items relate to anxiety and seven relate to de-
pression, each item is a Likert scale scoring from 0 to 3,
and this means that the overall score for either anxiety or
depression will be between 0 and 21; and 3) abuse and
mistreatment risk of AD patients, using the CASE instru-
ment, an 8-item screening tool designed to assess care-
givers for potential abuse. Answers are either given as ‘yes’
Chiatti et al. Trials 2013, 14:155
Page 3 of 11
or ‘no’, and an answer of ‘yes’ for a question equals one
point. A score of four or more is considered ‘abuse likely’,
but a score of one can also mean that abuse is likely,
depending on the question . An Italian validation of
this instrument is planned in a separate study at the end
of the trial.
Sample size calculation
An estimation of the sample size was carried out by con-
sidering the two main outcomes separately.
The first principal outcome is caregiver burden. A pre-
vious Italian study estimated that the level of burden of
AD patients' caregivers, as measured by the CBI ,
was equal to 32.5, with a standard deviation (SD) equal
to 18 . The planned sample size of 150 caregivers is
sufficient to detect an effect that lowers the CBI score to
24, with a SD equal to 12 in the treatment group and a
null effect in the control group. The statistical power was
fixed at 80%, with a 0.05 significance level and a drop-out
rate equal to 15%. A CBI score of 24 coincides with a
‘sentinel’ level beyond which it is suggested that care-
givers need to receive additional support from the health
care and social services.
The second principal outcome is actual days spent at
home by the AD patient in the past year. The hypothesis
that this outcome is the same in the treated and the un-
treated populations will be tested. The calculation was
made considering a type 1 error (α error) of 0.05, using a
one-tailed t-test and assuming a 10% difference between
values. Regarding this as the smallest effect of clinical rele-
vance, a sample of 150 patients per treatment group, with
a drop-out rate equal to 15%, will be adequate to achieve
an 80% probability of rejecting the null hypothesis.
Recruitment and screening
In the absence of a regional AD registry, lists of AD
patients will be requested from AEUs of the five health dis-
tricts (Pesaro, Ancona, Macerata, Fermo and San Benedetto
del Tronto). The AEUs were established in Italy in 2000
with the aim of improving the care pathways for AD pa-
tients. AEUs are multidisciplinary teams, usually led by a
neurologist or a geriatrician, with a double-fold task: 1)
performing a diagnosis of AD according to the most recent
clinical recommendations; and 2) prescribing cholinesterase
inhibitors, memantine and atypical antipsychotics under
the reimbursement scheme of the Italian health care sys-
tem. Thus, the patients followed by the AEUs are those
using the aforementioned drugs and receiving regular
follow-ups by the physicians working in the units. These
patients do not usually receive other care services, except
from AEUs as consequences of AD. The AEUs will provide
the lists of AD patients matching the inclusion criteria.
Only prevalent patients will be extracted and eligible to par-
ticipate in the study. Since local AD evaluation units do not
share ITsystems, a general list of patients will be created in
order to randomly select subjects to be enrolled in the
study. Inclusion and exclusion criteria will then be applied
to those patients.
Randomization, allocation and blinding
A letter with an invitation to participate in the project will
be sent to a list of potential participants, randomly extracted
from the AEU registers. A total of 640 invitations will be
sent, considering a response rate of 70% (a reasonably high
rate, since the project has been endorsed by the Italian re-
gional health system and several local patients' organiza-
tions). Families agreeing to be contacted will receive a home
visit by a nurse. Both caregivers and patients will be re-
quested to sign a full informed consent to participate in the
study. The nurses who will make the home visits and ad-
minister the questionnaires will be blinded at their first visit.
The allocation sequence will be generated using the stat-
istical software STATA (College Station, TX, USA). Dyads
in blocks of 15 and consequently enrolled will be sent by a
nurse coordinator in the five health districts directly to the
project manager (CC). In each block, five dyads will be allo-
cated to each arm. The randomization will be performed by
the project manager, who will not conduct any assessment
related to treatment outcomes or have any contact with line
staff involved in the intervention, in order to preserve allo-
cation concealment and prevent selection bias (Figure 1).
Case manager intervention
An ad hoc trained and hired case manager social worker
will systematically and comprehensively support each
patient-caregiver dyad in the UP and UP-TECH groups.
The underlying concept of case management is inspired by
the guidelines of the Case Management Society of America
. According to this definition, case management can be
defined as ‘a collaborative process of assessment, planning,
facilitation, care coordination, evaluation, and advocacy for
options and services to meet an individual’s and family’s
comprehensive health needs through communication and
available resourcesto promote
Before starting the trial, all case managers will attend an
8-day intensive and multidisciplinary course, which will ad-
dress the following subjects: 1) clinical, psychological and
social consequences of AD; 2) organization of health and
social care services for AD patients; 3) fiscal and law bene-
fits for AD patients; 4) counseling for caregivers; 5) meth-
odology of multidisciplinary work; 6) bioethics; and 7) use
of new technology for care. After the course, each case
manager will meet on a monthly basis with a senior social
worker, who will act as supervisor of the group in order to
share experiences and receive advice on the most difficult
Chiatti et al. Trials 2013, 14:155
Page 4 of 11
The following support will be provided by a case man-
ager: 1) at least three sessions of individual face-to-face
counseling, focusing on topics such as housing arrange-
ments, disease awareness and problem solving (following
an initial meeting, two reinforcing sessions will be held at
4 and 8 months); 2) monthly follow-up telephone calls; 3)
stress management training; 4) information about services/
aid/certification/subsidies offered by the Italian national
health service, municipal social services and local volun-
teer organizations (for example information on health
care services, support connecting to general practitioners,
health service units (medical specialists, hospital services)
and social services); and 5) coordination of professionals
working in different care settings, and between hospital
and community doctors in the case of hospital discharge.
All these services will be addressed with both parties of
the dyad and can be intensified when either the caregiver
or the patient shows signs of anxiety, stress or poor health,
which could also emerge during interviews. Each case
manager will handle up to 30 dyads, out of a total of 300
dyads (150 in the UP group and 150 in the UP-TECH
group). The placement of the case manager within the
network of existing health care and social services in the
community will be made following a thorough analysis of
care processes in order to facilitate their integration.
Technological device intervention
The project involves the testing of new technologies to
support the patient and their caregiver, and the advice of a
virtual information counter for technological aids and
Figure 1 The recruitment process in the UP-TECH project.
Chiatti et al. Trials 2013, 14:155
Page 5 of 11
adapting to the home environment. The technologies to
be employed are devices already widely used and mar-
keted, are simple to use, and do not require significant
technical expertise for installation and maintenance.
The technologies have been identified after a series of
preliminary focus groups with caregivers and will include
housing adaptations, such as luminous paths, home leav-
ing sensors, sensors to detect night falls, gas and water
leak sensors, and automatic lights. These devices will be
assembled by an external contractor and linked to a
single-board microcontroller, which will transmit alarm
messages to the caregivers in case of need. The assembled
devices will be assigned to subjects in the UP-TECH
group after a joint evaluation of the home by the case
manager and the engineer working in the virtual counter.
Although these technologies can appear as low-tech in
other industrialized countries, the degree of up-take of
these devices in the houses of older Italians is almost non-
Assistive technology will be installed by the case man-
ager with the support of expert technicians who will also
train the caregivers about their use (Figure 2).
Nurse home visits and light support
All dyads participating in the UP-TECH group will receive
three home visits by a specifically trained nurse. Home
visits will occur at enrollment (M0), 6 months (M6) and
12 months (M12). Each visit will occur with the following
steps: 1) telephone contact between the nurse and the
family caregiver; 2) collection of informed consent (only at
M0) and administration of the UP-TECH questionnaire;
and 3) brief counseling/training of the caregiver regarding
practical aspects of patient assistance, such as daily man-
agement of drug treatment, ergonomics of the home en-
vironment, stress management and care burden.
The creation of an information package for the 150 fam-
ily caregivers included in the control group, illustrating
the range of social and health services available in the local
community, is planned. The information package will be
delivered to the caregiver during home visits by the nurse.
These caregivers and their families will continue to receive
services in accordance with the usual care procedure,
which, as already mentioned, does not include any other
specific service from the health and social care systems.
Some patients might receive additional care services, but
Figure 2 The design of the UP-TECH kit.
Chiatti et al. Trials 2013, 14:155
Page 6 of 11
this does not occur within the framework of an integrated
case management program, and will depend on the pres-
ence of other pathological and social conditions.
All dyads will be interviewed using standardized tools.
The interviewers will be the same nurses conducting the
three home visits.
The first evaluation will also be the most in-depth. The
UP-TECH ‘questionnaire 1’ is divided into three parts: the
first focuses on AD patients (section A to C), the second
part concerns caregivers (section D to H), while the final
part measures the consumption of social and health care
resources by the dyad (section I).
A nurse, trained to collect data, will administer a modi-
fied version of the interResident Assessment Instrument
Contact Assessment (interRAI CA, Ann Arbor, MI, USA)
to the AD patient, when possible, or to the caregiver, who
will act as a proxy respondent . The interRAI CA is a
validated tool to support the decision-making process
when managing the home and/or palliative care of the
The instrument adapted from the interRAI CA will con-
tain items designed to investigate the following areas: sec-
tion A, general patient information: name, sex, date of
birth, health district affiliation, housing conditions, surgery
in the last 90 days and two main informal caregivers (ques-
tions about the benefits of the Italian legal system, Law
104/1992, were added); section B, screening information:
the ability to make everyday decisions, ADLs, dyspnea,
clinical status and perception of health status; and section
C, clinical evaluation: changes in the ability to make every-
day decisions, ability to understand other people, eyesight,
reported indicators of depressed mood, behavioral prob-
lems, IADL difficulties, changes in ADL independence,
disease diagnoses, falls, frequency of problems, pain, smok-
ing, assessment of nutritional status, mode of eating, the
highest stage of pressure ulcer, skin ulcer (not caused
by pressure), other skin problems, traumatic injuries, treat-
ments and services received, time since last hospitalization,
and number of emergency room visits.
The family caregiver will be given a questionnaire
consisting of five sections: section D, demographic and
socio-economic status: age, sex, housing, income and so-
cial network support using the Multidimensional Scale of
Perceived Social Support (MSPSS) ; section E, life-
style: information regarding diet, smoking and alcohol
consumption; section F, clinical evaluation: information
on the perception of caregiver depression and anxiety
(HADS) , the perception of well-being of the care-
giver (quality of life questionnaire, SF-12) , and the
presence of chronic diseases; section G. anthropometric
measurements, including control of blood pressure and
measurement of body mass index (BMI), via evaluation
of height and weight; and section H, the caregiving rela-
tionship: caregiver burden measured with the CBI 
and the risk of domestic abuse in the caregiving relation-
In the last section of the questionnaire (section I, con-
sumption of resources by the AD patient), the family care-
giver will be asked for information regarding: resource
consumption of the AD patient (for example drug therapy,
visits to general practitioners and specialists, use of home
nursing, and hospitalizations); use of treatment/care (for
example nurse and formal caregiver) paid for by the pa-
tient/caregiver dyad, expressed in number of hours per
week of treatment (or care); and the number of hours of
work lost by the caregiver (hours per week) to provide as-
sistance for the AD patient (productivity loss).
After the start of the study, at 6 months (M6) and 12
months (M12), respectively, a second and a third assess-
ment will be conducted. Twelve months after the end of
the trial (M24), follow-up telephone calls will be made
to study participants in order to assess the impact of the
interventions over the medium term.
Integration of collected data with Alzheimer Evaluation
The information collected through the questionnaire will
be integrated with information already held by the AEUs.
The following scales will be obtained for each patient:
MMSE, Clinical Dementia Rating (CDR) and Neuro-
psychiatric Inventory (NPI). Information concerning hos-
pitalizations and episodes of institutionalization in other
residential care facilities will also be retrieved from re-
gional hospital discharge and residential care databases.
The first step of the analysis will be exploratory in nature.
A descriptive analysis of the sample will be conducted
using uni- and bi-variate statistical analyses, with the aim
of verifying the comparability of the three study groups.
Significant differences between exposures and outcomes
will be compared using the chi-square test, Fisher’s exact
test (in the case of categorical variables), t-test or analysis
of variance (ANOVA) test (for comparisons of continuous
variables between groups according to a normal or non-
normal distribution). Additionally, to check possible selec-
tion bias, the characteristics of the subjects in the sample
will be compared to those of non-respondents for avail-
able variables (for example age, gender, place of living and
The primary outcome, caregiver burden inventory, will
be compared between the three groups using analysis of
covariance (ANCOVA). The analyses will adjust for vari-
ables which are non-homogenously distributed in the
three groups and control for other factors that the litera-
ture suggests are associated with the two outcomes (for
Chiatti et al. Trials 2013, 14:155
Page 7 of 11
example gender and age of caregivers, severity of demen-
tia, and use of private care workers) [46,47].
The primary outcome, number of days spent at home
by the AD patient during the observation period, will be
similarly analyzed using ANCOVA. The events of hospi-
talizations and institutionalization will also be analyzed
with the following: the distribution of events and event-
free survival (days spent at home) will be described for the
entire sample using Kaplan-Meier estimator modeling;
Mantel-Cox log-rank test or generalized Gehan-Breslow-
Wilcoxon test will be used to evaluate bivariate differences
in survival distribution between identified subgroups; Cox
proportional hazard modeling will be used to analyze the
multivariate effects of identified risk factors and other de-
terminants on time spent at home under the proportional
hazards assumption; and adjusted hazards ratio (HR) and
95% confidence intervals (CI) will be calculated to test the
direction and strength of the influence of individual fac-
tors on event-risk and event-free survival. The analyses of
outcomes will be intention-to-treat (ITT).
Multiple comparison issues
The issue of multiple comparisons will be carefully consid-
ered when investigating further specific questions. This
issue will be addressed using two strategies. First, statistical
adjustments for multiple comparisons will be used (for ex-
ample the Bonferroni correction for analyses with less than
10 comparisons or the Tukey's test in the other cases, both
available on STATA) to strengthen the criterion for judging
a result as significant and reduce the likelihood of false-
positive results. Second, future secondary and subgroup
analyses will always indicate all the subgroups and out-
comes considered in the trials. We will differentiate ex-
ploratory, sensitivity and other post hoc analyses from pre-
specified analyses of the primary and secondary outcomes
discussed in the protocol, and report them in any future
Health economics analysis
Cost, cost-effectiveness and cost-utility analyses will be
performed using the perspective of the Italian national
health service and municipalities. The cost-analysis will be
stratified according to allocation group (UP, UP-TECH and
control groups) and will include direct costs in terms of: 1)
time spent by each social worker, for each patient/caregiver
dyad; 2) time spent by other professionals with each patient;
3) time spent training social workers to perform the case
management intervention; 4) time and other costs of social
workers and nurses for tra-vel; 5) use of drugs for dementia
and related costs; 6) use of other drugs and related costs; 7)
use of health care and social services; 8) cost of other con-
sumables used for the interventions; and 9) cost of techno-
In a separate analysis we will also consider the social
costs of AD, defined as the sum of costs incurred pro-
viding formal treatment and patient care plus the cost of
informal care and the loss of productivity of caregivers.
The assistance provided by family caregivers will also be
assessed by valuing it equal to the salary of an unskilled
The availability of cost data, together with data collection
on health care outcomes, such as time to institu-
tionalization of the patient and the stress level/quality of life
of the caregiver, will allow a cost-effectiveness and cost-
utility analysis. We will consider the control group (light
care intervention) as the reference group for incremental
As outcomes measures for economic analysis we will use:
1) change in caregiver burden over a 12-month period; 2)
the number of institutionalizations; 3) hospitalizations; and
4) deaths. Since both the costs and the effects of the inter-
ventions will occur over a period of 1 year, it will not be
necessary to adjust for the time delay and to discount the
(ICERs) will then be calculated by taking the difference in
costs divided by the difference in the four outcomes be-
tween the groups. The ICERs will represent the additional
costs of gaining an additional unit of the above outcome
measures through the intervention owing to the case man-
agement intervention and the case management plus the
In a following step, probabilistic sensitivity analyses (PSA)
will also be performed on the three models using the soft-
ware,TreeAge Pro 2009 (Williamstown, MA, USA). Results
from the PSA will also be presented as an acceptability
curve, graphically illustrating the probability of the inter-
vention being cost-effective over a range of willingness to
A cost-utility analysis will estimate the ratio between the
cost of an intervention and the benefit it produces in
terms of caregivers' quality-adjusted life years (QALYs).
Utility will be measured using the SF-12 administered
during the nurse visits . The PSA of this model will
follow a similar procedure to that of the cost-effectiveness
The implementation of the UP-TECH project responds
to the increasing need to cope with the consequences of
the AD epidemic. It is in line with present policy and re-
search priorities at both Italian and European levels
Findings in this project are intended to support both
health care and social service professionals and policy-
makers in the enactment of future programs, addressing
the increasing needs of AD patients and their caregivers.
The rationale behind the project is that, despite the
Chiatti et al. Trials 2013, 14:155
Page 8 of 11
growing literature in this area, several controversies still
need to be resolved and effective options need to be laid
out in order to both avoid the institutionalization of AD
patients and the burn-out of informal caregivers .
The project gathers the existing knowledge and related
strategies in the area of dementia care, that is, the use of
case management programs [8,15,16,26], new technolo-
gies [8,20,26], preventive home visits  and efforts to-
ward integration of existing services [27-30], and tries to
integrate them in an ambitious holistic design.
Possible limitations of the design should be mentioned.
As the caregiver-patient dyads are allocated after the full
consent, blinding is not required during the first home
visit; however, blinding cannot be guaranteed during the
second and third visits, or during the follow-up telephone
call. Since the nurses will engage with patients and care-
givers in long conversations, it is likely that they will be
told about the social worker intervention or they will no-
tice the technological toolkit installed in the home. In
order to minimize the risk of performance and ascertain-
ment bias, we will provide an ad hoc training course to
nurse assessors, and we will keep as separated as possible
the professionals intervening on the patients and care-
givers (the social workers) from those assessing the out-
comes (the nurses). In addition, we preserved the solidity
of the study by choosing as one of the two primary out-
comes, the number of days free from hospitalizations and
other institutionalization episodes, a measure which is not
likely to be influenced by an eventual un-blinding of the
Regarding the use of new technologies, the UP-TECH
project does not entail the use of highly complex and in-
novative devices, but aims to test the effectiveness of
simple marketed technological devices combined with
case management and user-centered strategies.
Another key aspect of this investigation is the combin-
ation of research together with the implementation of a
patient-based IT system in the Marche region of Italy.
This will consolidate information, allowing community
and hospital doctors, as well as social workers and other
professionals, to coordinate health care and social services
for AD patients and their caregivers. This IT-based inte-
gration of information is therefore expected to increase
the efficiency and efficacy of deploying health care and so-
cial services, which is especially important in an environ-
ment of increasing demand and decreasing resources.
Finally, the costs and the cost-effectiveness of different
interventions will also be evaluated through detailed ana-
lyses of formal and informal resource consumption during
the study. The evaluation will adopt the perspectives of
both the Italian national health service and of Italian soci-
ety. This will allow testing of the hypothesis that the cost-
effectiveness of the programs addressing AD patients in
the community also remains even when considering
hidden costs of care, such as caregiving burden and loss of
productivity. This is expected to provide sound and defini-
tive evidence on the costs and cost-effectiveness of pro-
grams targeting AD patients in the community, thus
allowing a comparison of institutional and community-
based care solutions, and address future reforms of the
local and national welfare system.
The trial will start recruiting on 1 December 2012 and is
scheduled to continue until 31 March 2014.
CBI: Caregiver Burden Inventory; ADL: Activities of daily living; AEU: Alzheimer
Evaluation Unit; ANCOVA: analysis of covariance; ANOVA: Analysis of variance;
BMI: Body mass index; CDR: Clinical Dementia Rating; CI: Confidence
intervals; HADS: Hospital Anxiety and Depression Scale; HR: Hazards
ratio; IADL: Instrumental activities of daily living; ICER: Incremental
cost-effectiveness ratios; INRCA: Italian National Research Center on Aging;
ITT: Intention-to-treat; interRAI CA: InterResident Assessment Instrument
Contact Assessment; Istat: Italian National Institute of Statistics; IT: Information
technology; MMSE: Mini-mental state examination; MSPSS: Multidimensional
Scale of Perceived Social Support; NIA-AA: National Institute on
Aging-Alzheimer's Association; NPI: Neuropsychiatric Inventory;
PSA: Probabilistic sensitivity analyses; QALY: Quality-adjusted life year;
SD: Standard deviation.
The authors declare that they have no competing interests.
CC: study concept; project manager of the study; preparation of study
protocol; drafting of manuscript. FM: principal investigator of the study;
preparation of study protocol; critical review of manuscript. JMR: preparation
of study protocol; critical review of manuscript; English language editing. AC:
preparation of study protocol; critical review of manuscript. OS: preparation
of study protocol; critical review of manuscript. LS: preparation of study
protocol; critical review of manuscript. FL: preparation of study protocol;
critical review of manuscript. All authors read and approved the final
This study is funded by the Marche Region through the Special Fund for
Dependency Care managed by the Italian Ministry of Welfare (il progetto UP-
TECH è realizzato dalla Regione Marche in collaborazione e con il contributo
dell’INRCA Ancona attraverso il finanziamento del Fondo Nazionale non
Autosufficienza, 2010). The funder plays no role in the design of the study, in
the collection, analysis and interpretation of data, or in the decision to
submit the manuscript for publication.
* This paper was prepared on behalf of the UP-TECH multidisciplinary
research group. Social workers: Diletta Baldassarri, Luigina Bitti, Aurora Carosi,
Maila Sabbatini, Elisabetta Paolasini, Tania Fiori, Cinzia Fronzi, Simona
Giacchetta, Valeria Giacomini, Laura Giovagnoli, Giuli Lattanzi, Anna Maria
Manca, Ida Marinelli, Valeria Pigini, Marina Pignotti, Maria Chiara Proietti,
Antonia Quarticelli, Martina Rovedi, Letizia Tasso, and Valentina Valeri. Nurses:
Andrea Antonioli, Mariella Barabucci, Mara Bassani, Paola Bollettini, M Cristina
Bruttapasta, Carla Buccolini, Rosa Carangella, Franca Carboni, Daniela
Ceccolini, Patrizia D'Incecco, Mariangela Di Felice, Lara Dini, Giordano Gioia,
Giuseppe Di Prima, Giancarlo Giusepponi, Cesarina Lanciotti, Alessia Loffreda,
Oriana Luciani, Laura Mariani, Francesco Mastrorilli, Roberto Moroni, Izabela
Piatkowska, Roberta Rucoli, Giampaola Scoccia, Nives Teodori, and Tiziana
Tonelli. Physicians: Rossano Angeloni, Rosa Anna Bratti, Giuseppe Bonafede,
Severino Lorenzetti, Cristina Paci, Giovanna Picciotti, Donella Pezzola,
Vincenzo Rea, Vittorio Scialè, Mario Signorino, Francesca Sorvillo, and Pia
Francesca Tomassini. Psychologists: Alessia Ciccola and Loena Cionfrini. Social
services managers: Daniela Alessandrini, Antonio De Santis, Brunetta Formica,
Giuliano Tacchi, Silvia Tortorelli. Marche Regional Authority: Gemma
Marchegiani and Giovanni Santarelli. UP-TECH scientific committee: Giorgio
Chiatti et al. Trials 2013, 14:155
Page 9 of 11
Caraffa, Filippo Cavallo, Lucia Di Furia, Antonio Lacetera, Claudio M Maffei,
Lamberto Manzoli and Demetrio Postacchini. INRCA working group: Roberta
Bevilacqua, Anna Rita Bonfigli, Franco Bonfranceschi, Silvia Bustacchini,
Marina Capasso, Laura Cassetta, Patrizia Civerchia, Gianluca Furneri, Cinzia
Giuli, Paolo Marinelli, Gabriella Melchiorre, Maria Elena Moraca, Andrea
Principi, Cristina Rocchetti and Daniela Vincitorio. Virtual counter for
technologies: Krystian Bartulewicz and Lorena Rossi.
Received: 4 December 2012 Accepted: 14 May 2013
Published: 28 May 2013
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Cite this article as: Chiatti et al.: The UP-TECH project, an intervention to
support caregivers of Alzheimer’s disease patients in Italy: study
protocol for a randomized controlled trial. Trials 2013 14:155.
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