Complementary Therapy in Home Palliative Care Patients and Their Caregivers
Complementary Therapy in Home Palliative Care Patients and Their Caregivers
Introduction:

 There is an increase on cancer prevalence and, consequently, a higher number of people that
 require palliative care, making an influence on the family and the main carer.

 Objectives:

 -  To evaluate the efficiency and cost-effectiveness of a music intervention program,
 applied as a complementary therapy, in oncological palliative care patients and carers
 at home, compared to current treatment.

 -  To assess if patients in the intervention group submit significant differences
 regarding: pain, anxiety, depression, modo, insomnia, and life quality.

 -  To assess if carers in the intervention group present significant differences regarding
 the Caregiver Burden Scale and life quality.

 -  To evaluate patients and carers satisfaction on the therapeutic intervention.

 -  To estimate the cost-effectiveness of the intervention.

 Method:

 Randomised, double-blind, multi-centre clinical trial in the field of primary health care,
 conducted in 5 clinical management units belonging to Málaga-Guadalhorce health district and
 performed in oncological palliative care patients and carers. Two samples of 40 palliative
 care patients and two samples of 41 carers. The intervention group will undergo a 7-days
 intervention with music sessions, the control group will be given seven sessions of
 retraining in therapeutical education. Objectives will be evaluated through the following
 tools: Edmonton Scale, Symptom Assessment System, EORTC QLQ-C30, Caregiver Burden Scale,
 Pittsburgh Sleep Quality Index, Accelerometer, Epworth Sleepiness Scale (ESS), The Quality of
 Life Family Version, Client Satisfaction Questionnaire and Economical valuation.

 To assess the objectives evaluations will be performed through home visit, both
 pre-intervention and a week after the beginning of the intervention for both groups. A
 follow-up visit will be made a month after the intervention to regard some economical
 parameters.

 Statistical analysis:

 The basal values of both groups will be compared. These values will be compared before and
 after the intervention, in the control and intervention group through Student t-test for
 normal continuous variables, and through Wilcoxon t-test for paired data in not normal
 continuous variables. In addition to the bivariated analysis, a multiple lineal regression
 will be carried out. The economical valuation will be a cost-effectiveness analysis. For each
 group we will measure cost, incremental cost, AVAC effectiveness, incremental effectiveness,
 dominance and, in case there is none, the results will be expressed in terms of incremental
 cost-effectiveness. To assess the costs, direct sanitary costs and intervention related costs
 will be considered.

 SPSS 23 will be the statistical software to use, along with Epidat 3.01. 95% confidence range
 will make p values under 0,05 (p<0.05) statistically significant.
Background and status.

 Cancer presents an enormous challenge to the world public health. Every year, 8 million
 people die because of the disease, meaning it´s one of the main causes of death in the world
 and the pathology changes the patient in all their levels: physical (appearance, treatment
 consequences), emotional (reactions variability, feelings, distress), cognitive (personality
 and character, ways of facing the problem and adaptability), social and spiritual. It
 produces suffering on an individual, familiar and social level.

 An estimation of 50-60% of the people that perish in Spain, based on age and death causes,
 does so after the disease reaches an advanced stage, being terminal. Terminal patients
 require great amounts of nursing and health care, being these needs very heterogenic and
 implying both sanitary and social resources.

 According to the Andalusian Plan for Palliative Care estimations, Andalusian population
 susceptible to receive palliative care stands between a minimum of 31.553 and a maximum of
 62.887 inhabitants.

 World Health Organization (WHO) defined palliative care as: 'An approach that improves the
 quality of life of patients and their families facing the problem associated with
 life-threatening illness, through the prevention and relief of suffering by means of early
 identification and impeccable assessment and treatment of pain and other problems, physical,
 psychosocial and spiritual'.

 A revision carried out in 2011 by the World Federation of Music Therapy (WFMT) defined music
 therapy as 'The professional use of music and its elements as an intervention in medical,
 educational, and everyday environments with individuals, groups, families, or communities who
 seek to optimize their quality of life and improve their physical, social, communicative,
 emotional, intellectual, and spiritual health and wellbeing'.

 Integrating music therapy into palliative care intervention could help patients and
 caregivers to deal with some of the physical, emotional, social and spiritual needs they
 face: making changes in pain and anxiety perception easier, improving the mood, relaxing,
 enabling better emotional expressions, connecting with spirituality and offering support
 during mourning.

 To perform adequate care services at home, a main caregiver is needed to guarantee that
 patients have all their basic needs cover, follow the scheduled treatment for the symptoms,
 get continuous family and social support and attention, specially at the end. But the
 caregiver's health can be affected, specially if subjected to an overload of work or
 adaptation to rapid changes in the person taken care of, affecting its quality of life.

 For the most optimal performance of the caregiver, it is needed that they are also
 recognised. A systematic review in 2008 showed a lack of evidence-based interventions that
 support attention given to the caregivers of cancer patients, encouraging nurses to keep
 researching and putting to test intervention that reduce the burden on caregivers. However,
 several interventions in the attention to caregivers of terminal or palliative care patients
 proves their efficacy. Regarding the use of music therapy to achieve an improvement on the
 caregiver wellbeing, very few studies can be found.

 Bibliography offers more and more studies and systematic reviews regarding music therapy in
 the intervention of cancer patients under palliative care, where the main goal is the study
 of the music therapy as a complementary treatment and a no-pharmacological treatment of
 anxiety, depression, pain, quality of life and physiological symptoms, pointing to its
 efficacy.

 Kordovan et al. (2016) performed a prospective review of viability, acceptance and possible
 beneficial effects of music therapy in hospitalised terminal cancer patients, and the authors
 summarised that music therapy, especially receptive methods, are feasible and well regarded
 among these patients. A controlled randomised trial performed with hospitalised palliative
 care patients revealed music therapy to be an effective treatment to promote relaxation and
 wellbeing for the patients. The music therapy didn't differ from the control treatment in
 terms of pain reduction, but it was significantly different in the fatigue aspect of quality
 of life scale , being considerably lower. Control treatment was verbal relaxation.

 On economic aspects, Keenan A., Keithley JK. (2015) made an integrating review about music
 effect in adults' cancer pain, stating a limited evidence of music therapy in pain treatment.
 Integrative methods using music may represent an important intervention that nurses can
 suggest as an economical, non-toxic and easily available to potentially reduce cancer pain.
 Efficiency wise, several publications point to a reduction in expenses mainly due to a lower
 medication intake, and it may as well mean a reduced number of professional attention and
 hours dedicated to deal with the symptoms.

 Another systematic review by Qi He Mable L., Drury VB., Hong PW. (2010) showed the
 development of two important finding: music therapy can and must be used in palliative
 environments to promote social interaction and communication with family, friends, other
 patients and health practitioners; and it may as well be used to provide support to patients'
 needs. Through music therapy, patients noticed an improvement on social interaction and
 communication with their surroundings and a better way to satisfy their physical,
 psychological and spiritual needs.

 In a Cochrane review from Bradt et al. (2016), authors concluded that music intervention can
 bring positive results on anxiety, pain, mood and quality of life in cancer patients, but the
 results must be read with caution as the bias risk is high.

 In a study carried out by Gallager et al. (2017), it was proposed to understand the insight
 of family members regarding music therapy undertaken by the palliative care patients. Out of
 50 participants, 82% indicated an improvement for both the relative and the patient in stress
 management, mood and quality of life, the session being rated as extremely useful in the 80%
 of cases, and 100% of them recommended more sessions. Patients reported a statistically
 significant improve regarding pain, depression, distress and mood. The study concludes that
 palliative patients´ relatives inform of an improvement on both patients and relatives, but
 more research is needed to fully comprehend the beneficial effects on the family.

 This study proposes using music therapy on both patients and caregivers, differing in the way
 of choosing the music. Whereas most studies in the bibliography resort to picking relaxing
 music among different categories, such as jazz, folk or country, we aim to ask the
 participants to choose the music the want to listen to. This study will consider that the
 same genre can vary in the options available for the patients, triggering different emotions
 in different people depending on personal experiences. Although people can distinguish
 between sad and cheerful tunes, most people have preferred music that cheer us up or saddens
 us and we use it to our convenience, so the study will focus on the music that makes each
 patient feel better, assuming than that is the key to achieve better results.

 This clinical trial will consider all recommendations from the authors of the Cochrane 2016
 review to avoid bias.

 Despite the high potential benefit that it could be to optimise medication intake and reduce
 sanitary resources expenditure, the evidence on cost-effectiveness in music intervention is
 very limited, so this study will also try to determine the efficiency of the intervention.
 Economic evaluation methods will be applied, along with a helping tool to determine, through
 decisions taken, the optimal use of sanitary resources and allowing the gathering of feedback
 of the impact of the intervention for both the organisation and the social program.

 General objective:

 - To evaluate the efficacy and cost-effectiveness of a music intervention program applied as
 a complementary treatment on palliative care for oncological patients and caregiver in a
 domestic environment, compared to standard treatment.

 Specific objectives:

 -  To assess if the oncological patients in palliative care included in the intervention
 group present significant differences with the control group regarding: pain, anxiety,
 depression, mood and insomnia.

 -  To evaluate if the oncological patients in palliative care included in the intervention
 group present significant differences with the control group in their quality of life.

 -  To assess if the caregivers of the intervention group patients present significant
 differences with those of the control group regarding the Caregiver Burden Scale and
 quality of life.

 -  To value caregivers and patients' satisfaction with the intervention.

 -  To estimate the sanitary cost associated to the music intervention program compared to
 traditional sanitary interventions.

 Methodology:

 Randomised, double-blind, multi-centre clinical trial in the field of primary health care,
 conducted in 5 clinical management units belonging to Málaga-Guadalhorce health district and
 performed in oncological palliative care patients included into the Assistance Procedure of
 Palliative Care in digital health history (DIRAYA) and their unofficial caregivers.

 -  Subjects acquisition will be performed randomly through a phone list obtained using the
 program Epidat 3.1, taking the required number of palliative care patients, contacting
 each of them and evaluating if inclusion criteria are met, offering the chance of taking
 part of the intervention and handing over the correspondent information document. In
 case the patient accepts, a consent form must be signed. In case the patient has an
 unofficial caregiver, they will be offered to take part in the study as well, giving
 them the information sheet and signing the consent form specific for the caregiver in
 case they accept.

 -  The randomisation mechanism that has been chosen is as follows: letters will be ready
 with 'you have been included in the intervention group' and 'you have been included in
 the control group' in a number that meet the requirements, they will be put into opaque
 envelopes, shuffled and numbered. Participants will be assigned a participation number
 and the researcher in charge of randomisation will pick and open the envelope assigned
 to the participant number. This system ensures the number is fixed for each group and
 prevents tampering.

 The palliative care patient and the caregiver are offered to participate and, if both accept,
 they will be offered an envelope that will be valid for both, taking part into the study in
 the same group. If only one of the two accepts, they will be offered an envelope as well.
 Participants will be taken until the desired number of cases is reached.

 Once the researcher in charge of randomisation knows which groups the patient and the
 caregiver belong to according to the envelope, they will be informed of the procedure they
 will undergo without knowing their belonging to either the control or the intervention group.

 • Sample size: the most relevant variable to be considered is anxiety for palliative care
 patients. In Bradt et al. (2016) revision it was presented with a standard deviation of 1'8
 in a similar sample using a scale with a wider range than the one used in this study.
 Previous bibliography shows significant differences after music intervention, with a specific
 estimation of difference in 7 (29% of standard deviation). A research using the Edmonton
 Scale (in oncological patients, treatments with ginseng) showed a value of 0-83 points with a
 standard deviation of 2.34 (35% of standard deviation). If we consider as clinically relevant
 a decrease of 2 points in the anxiety before-after, expecting a standard deviation of at most
 2.5 in our population; with an alpha error of 0.05 and a beta of 0.10 2 samples of 33
 subjects are needed, choosing the ration for the samples in 1:1. A 20% increase, making it 2
 samples of 40 subjects, would be desirable to avoid patients loss/dropping the intervention.

 According to Hanser et al. (2011), there is an increase in the caregivers´ satisfaction with
 the music therapy, with a standard deviation of 1.33 on relaxation, 1.87 on comfort, and 1.23
 in happiness. If we take a 1-point increase in caregivers' happiness as relevant, 2 samples
 of 34 carers would be needed. A 20% increase, making it 2 samples of 41 subjects would be
 desirable to avoid subjects loss/dropping the intervention.

 -  Procedures by group

 -  Control group: the regular treatment will be carried out according to the
 Andalusian Plan of Palliative Care of the Health Counsel, following the standards
 and recommendations from the Minister of Health and Social Policy Palliative Care
 Units. It will consist on a complete initial valuation of the palliative care
 patient and the caregiver using Virginia Henderson's 14 fundamental needs (Need
 Theory) and the subsequent treatment and follow-up care plan for problems and
 symptoms detected; a therapeutic education about eating and hydration, lessons
 about exercise and leisure, medication, effective communication, skin care,
 prevention and treatment of constipation, and sleep hygiene will be also carried
 out. These patients and caregivers will receive the basic therapeutic education in
 a mp3 player or mobile phone (audio document shared on Drive) to be repeated and
 listened to in daily sessions of 30 minutes for 7 days. This way, the patients
 won´t know the group they are included in, and the nurses managing and evaluation
 the patients will also be blind.

 -  Intervention group: subjects will receive conventional health assistance,
 complemented by music therapy activity consisting in pre-recorded preferred music,
 for both patients and caregivers. Music will be chosen among the one that make each
 of the subjects feel good. It will be reproduced through an mp3 player or mobile
 phone (using the Premium Spotify program) in daily sessions of 30 minutes for 7
 days.

 -  To evaluate the expected objectives, valuations by means of home visits will be made,
 both preintervention and a week after the start of the intervention, for both groups. A
 home visit will also be done after a month to assess economic parameters.

 -  The following valuation scales will be used: Edmonton Scale, Symptoms Assessment System,
 EORTC QLQ-C30, Caregiver Burden Scale, Pittsburgh Sleep Quality Index, Epworth
 Sleepiness Scale (ESS), The Quality of Life Family Version, Client Satisfaction
 Questionnaire, and Economic valuation.

 -  Statistical analysis: a descriptive study of the collected factors will be carried out
 by means of media and standard deviation for normal continuous variables; calculating
 confidence interval for punctual estimations; through median and interquartile range in
 not normal continuous variables; and frequencies and percentages in categoric variables.
 Adjustment to normality will be determined by the Shapiro-Wilk test. The basal values of
 both groups will be compared before and after the intervention, in the control and
 intervention group through Student t-test for normal continuous variables, and through
 Wilcoxon t-test for paired data in not normal continuous variables. In addition to the
 bivariated analysis, a multiple lineal regression will be carried out, where the
 dependant variables will be: pain, anxiety, depression, mood, insomnia and quality of
 life; the independent variables will include intervention, sociodemographic (sex, age,
 studies, civil status) and clinical (pathology, palliative care time) variables of the
 subjects. The economic valuation will be a cost-effectiveness analysis, following the
 recommendations proposed in the guide to evaluate economic performances in health
 technologies. For each group, we will measure the cost, incremental cost, AVAC
 effectiveness, incremental effectiveness, dominance and, in case there is no dominance,
 results will be showed as an incremental cost-effectiveness ratio. To assess the costs,
 direct sanitary costs and intervention related costs will be considered. Sanitary
 resources costs will be estimated using the public prices set by the SSPA58. The cost of
 direct resources used during the intervention will be estimated by means of their
 recommended retail price (RRP). To calculate the AVAC, the EuroQol-5D-5L Questionnaire
 will be used. Uncertainty variables analysis will be subject to univariant and
 polyvariant sensitivity analysis.

 In the event of finding statistically significant data in normal variables, the confidence
 range will be calculated on 95%, allowing the estimation of values where the difference is
 found. SPSS will be the statistical software to use, along with Epidat 3.01. 95% confidence
 range will make p values under 0,05 (p<0.05) statistically significant.

 • This study is in agreement with the current ethic recommendations:

 -  Principles of the Declaration of Helsinki (1975) reviewed in 2013 (AMM), ethical
 principles for researching in human, adopted by the 64th Genera Assembly, Fortaleza,
 Brazil, October 2013).

 -  All personal data and information obtained in this study are confidential and will be
 deal with in accordance to the EU regulation 2016/679 of the European Parliamentary
 Group and the Council on April 27th of 2016 for General Data Protection Regulation
 (GDPR).

 -  Law 41/2002 from November 14th, basic regulation law for patient´s autonomy, obligations
 and rights regarding information and clinical documentation. Participation will be
 voluntary, and a written consent form must be signed to be included in the study.
 Patients and caregivers will be treated with maximum respect, without economic,
 religious, ethnic or sexual orientation discrimination. All participants will be
 informed both oral and written about the content and characteristics of the study,
 remarking the voluntary character and the possibility of rejecting taking part in the
 study, or dropping from it in any moment if it is desired. All data obtained will be
 private and confidential, its use reserved only for the purposes of this study and being
 destroyed afterwards.

 The investigation Project hast been accepted by the Ethic Committee for Provincial Research
 in Malaga. During the study, the Code of Good Scientific Practice will be upheld.
Inclusion Criteria:

 -  Oncological patients in palliative care at their homes, older than 18 years old, and
 their formal caregiver, in case they have one.

 -  Patients who have given their consent to be included in the study.

 Exclusion Criteria:

 -  Oncological patients in palliative care at their homes, with diseases in an advanced
 stage and a short life expectancy (last days).

 -  Oncological patients with late stages dementia or psychological pathologies, not being
 capable of taking conscious decisions.

 -  Oncological patients with hypoacusis or profound deafness, hindering the use of the
 mp3 player or mobile phone.