A Feasibility Trial of a Brief Positive Affect Intervention to Improve the Effectiveness of Influenza Vaccine Response in Older Adults.
Phase: NA
Conditions: Vaccination; Infection
Sponsor: University of Nottingham

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
 
 
 
 
 
 
 
A Feasibility Trial of a Brief Positive Affect Intervention to 
Improve the Effectiveness of Influenza Vaccine Response in 
Older Adults. 
 
Final Version 1.1 
21st August 2017 
 
 
 
Short title: 
Mood and Influenza Vaccine Response: A 
Feasibility Trial 
 
 
Trial Registration: 
www.clinicaltrials.gov Identifier: NCT03144518 
 
 
IRAS Project ID: 
226429 
 
 
Trial Sponsor: 
 
University of Nottingham 
 
 
Sponsor reference: 
17039 
 
 
Funding Source: 
National Institute for Health Research School for 
Primary Care Research (NIHR SPCR).

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
TRIAL / STUDY PERSONNEL AND CONTACT 
DETAILS 
 
Sponsor: 
University of Nottingham 
Contact name 
Ms Angela Shone 
 
Head of Research Governance 
 
Research and Graduate Services 
 
King’s Meadow Campus 
 
Lenton Lane 
 
Nottingham 
 
NG7 2NR 
Email: sponsor@nottingham.ac.uk  
 
Chief investigator:  
Mr Kieran Ayling 
Research Fellow 
Division of Primary Care 
Tower Building 
University of Nottingham 
Nottingham 
NG7 2RD 
Email: kieran.ayling@nottingham.ac.uk  
Phone: 01158466908 
 
Co-investigators:  
Professor Kavita Vedhara 
 
Professor of Health Psychology 
University of Nottingham 
 
Division of Primary Care 
 
Tower Building 
University Park 
Nottingham, NG7 2RD 
 
Phone: 0115 846 6931 
 
 
Email: kavita.vedhara@nottingham.ac.uk  
 
Dr Heather Buchanan 
Senior Lecturer in Health Psychology 
Division of Rehabilitation & Aging, 
University of Nottingham 
Nottingham 
NG7 2UH 
Email: heather.buchanan@nottingham.ac.uk  
 
Dr Lucy Fairclough 
Lecturer in Immunology 
School of Life Sciences,  
University of Nottingham,  
Nottingham  
NG7 2UH 
Email: lucy.fairclough@nottingham.ac.uk 
 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
 
Associate Professor Paddy Tighe 
Associate Professor in Immunology 
School of Life Sciences,  
University of Nottingham,  
Nottingham 
NG7 2UH 
Email: paddy.tighe@nottingham.ac.uk  
 
Professor Ian Todd 
Professor in Immunology 
School of Life Sciences,  
University of Nottingham,  
Nottingham, 
NG7 2UH 
Email: ian.todd@nottingham.ac.uk 
 
Dr Simon Royal 
General Practitioner 
Cripps Health Centre,  
University of Nottingham, 
Nottingham 
NG7 2QW 
Email: simon.royal@nhs.net 
 
Dr Mark Wetherell 
Reader in Psychobiology & Health Psychology 
Department of Psychology,  
Northumbria University,  
Northumbria 
NE1 8ST 
Email: mark.wetherell@northumbria.ac.uk 
 
Dr Grazziela Figueredo 
Advanced Data Analysis Centre, 
School of Computer Science, 
University of Nottingham 
Nottingham 
NG8 1BB 
 
 
Email: grazziela.figueredo@nottingham.ac.uk 
 
Trial / Study Statistician: 
Dr Grazziela Figueredo 
Advanced Data Analysis Centre, 
School of Computer Science, 
University of Nottingham 
Nottingham 
NG8 1BB 
 
Phone: 01159514923 
 
 
Email: grazziela.figueredo@nottingham.ac.uk  

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
 
 
Trial / Study Coordinating Centre:  
Division of Primary Care 
School of Medicine 
Queen’s Medical Centre 
Nottingham 
NG7 2UH 
 
 
 
 
 
 
 
 
 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
SYNOPSIS 
 
Title 
A Feasibility Trial of a Brief Positive Affect Intervention to Improve the 
Effectiveness of Influenza Vaccine Response in Older Adults. 
Short title 
Mood and Influenza Vaccine Response: A Feasibility Trial 
Chief Investigator 
Mr Kieran Ayling 
Objectives 
To assess the impact of a brief positive affect intervention on mood, 
immune function, and antibody response to influenza vaccination in older 
adults. This feasibility trial will also allow data collection on exploring 
recruitment, attrition, intervention engagement, and practicality of 
collecting clinical data available through electronic records to inform the 
design of a future definitive trial. 
 
Trial Configuration 
2 arm parallel randomised controlled trial, with post-trial qualitative 
interviews/focus groups 
Setting 
Primary Care 
Sample size estimate 
As a feasibility study, the sample size has been selected to inform the 
design of a future definitive RCT allowing us to examine recruitment 
uptake levels, attrition, intervention engagement, and suitability of data 
collection methods. It is not our aim to be powered to detect effects in 
vaccine specific outcomes (e.g., antibody responses, rates of flu like 
illness) but to provide initial effect size estimates for a future larger RCT. 
 
However, our sample size will be sufficient to provide adequate power to 
detect pre-post differences in positive affect between conditions. A 
sample of 45 participants would be needed per arm to provide 95% 
power to detect pre-post differences. We will, therefore, aim to recruit 55 
participants per condition to allow for reasonable attrition.  
 
Number of participants 
Approximately 110 older adults (65-85 years old). The reason for having 
an upper limit of 85 years is that after this time immune function can vary 
much more greatly across individuals – including those over 85 could 
potentially obscure/alter results and their generalisability. 
 
For Staff Interviews – Approximately 8 health care professionals 
(including GP’s, practice manager, health care assistants, nurses etc.) 
who worked in the recruiting practices. 
 
Eligibility criteria 
For Feasibility Trial: 
Inclusion criteria 
Males and Females aged 65-85 years (inclusive) 
Received influenza vaccination for the 2016/17 season 
Eligible to receive 2017/18 influenza vaccination as part of usual care 
Ability to give informed consent  
 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
Exclusion criteria 
Males and Females aged less than 65 or over 85 years (exclusive) 
Did not receive influenza vaccination for the 2016/17 season 
Ineligible to receive 2017/18 influenza vaccination as part of usual care 
Unable to provide informed consent 
Deemed by health care provider to be:  
Too physically frail to participate 
Diagnosed with dementia or other cognitive condition which would make 
participation difficult 
Insufficient command of English language 
Influenza vaccination contraindicated 
Sufficiently impaired of hearing or vision that exposure to the intervention 
or control video content as intended would be compromised 
Those for whom the collection of blood samples is contraindicated. 
 
For Post-Trial Staff Interviews: 
Inclusion criteria 
Member of staff at a GP practice site involved in the feasibility trial 
Aware of and observed aspects of the feasibility trial at their site 
 
Exclusion criteria 
Not staff at a GP practice site involved in the feasibility trial 
Unaware of or did not observe any aspect of the feasibility trial at their 
site 
 
Description of 
interventions 
Trial will focus on a brief mood intervention (video based approx.15-20 
mins length) delivered prior to receipt of the trivalent influenza 
vaccination (delivered as part of usual care). Pre- and post-intervention 
mood questionnaires will be collected. Saliva samples will be collected 
immediately pre- and post-intervention. Blood samples to be taken at 3 
times points (baseline, approximately 4 weeks post-vaccination and 16 
weeks post-vaccination) to assess vaccine response. 
 
Experimental Intervention: Video package designed to induce an 
increase in positive mood in older adults. Includes comedy clips, uplifting 
music and positive imagery. 
  
Active Control: Video package matched in length and type to 
experimental intervention but not designed to influence mood. 
 
Duration of study 
The trial will be start alongside the 2017/2018 influenza vaccination 
schedule (i.e., August/September 2017). Participants will be involved for 
approximately 4 and a half months, which includes all follow-ups. 
Participants will be asked to give consent for medical records to be 
examined at 6 months post-vaccination. The main parts of the trial will 
end when the final participant completes their 16 week post-vaccination 
follow-up (approx. March 2018), although post-trial focus 
groups/interviews will occur and medical records will be examined up to 
6 months post-vaccination (approx. May 2018). 
 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
Randomisation and 
blinding 
1:1 Randomisation, computer generated. Participants blind to nature of 
other conditions. Researchers and outcome assessors blind to 
participant allocation until end of trial. 
 
Outcome measures 
Psychological outcomes will be measured using questionnaire self-report 
measures. Vaccine and immune response will be measured using a 
variety of immunological parameters derived from blood and saliva 
samples. Feasibility measures (e.g., recruitment uptake, attrition) will be 
recorded by the chief investigator. Post-trial focus groups/interviews will 
be qualitatively analysed for themes using thematic analysis. 
 
Statistical methods 
While many outcomes of interest will be descriptive in nature (e.g., 
attrition, recruitment rates), between arm comparisons will be made on 
several primary and secondary outcomes (positive affect, antibody 
response, secretory IgA concentration – which is a broad non-specific 
marker of immunological function, health service utilization) using 
appropriate statistical tests (e.g., between group t-tests). Intention-to-
treat analyses will be favoured where appropriate.  
Qualitative post-trial interviews/focus groups will be analysed using 
thematic analysis. 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
ABBREVIATIONS  
 
 
 
AE 
Adverse Event 
 
 
CI 
Chief Investigator overall 
 
 
CRF 
Case Report Form 
 
 
DMC Data Monitoring Committee 
 
 
GCP 
Good Clinical Practice 
 
 
ICF 
Informed Consent Form 
 
IgG 
Immunoglobulin Serotype G 
 
 
NHS 
National Health Service 
 
 
PI 
Principal Investigator at a local centre 
 
PIS 
Participant Information Sheet 
 
 
REC 
Research Ethics Committee 
 
R&D 
Research and Development department 
 
 
SAE 
Serious Adverse Event 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
TABLE OF CONTENTS 
 
 
SYNOPSIS ................................................................................................................................. 5 
Inclusion criteria 
5 
Exclusion criteria 
6 
Inclusion criteria 
6 
ABBREVIATIONS ................................................................................................................... 8 
TRIAL / STUDY BACKGROUND INFORMATION AND RATIONALE ..................... 11 
TRIAL / STUDY OBJECTIVES AND PURPOSE ............................................................. 12 
PURPOSE 
12 
PRIMARY OBJECTIVE 
12 
SECONDARY OBJECTIVES 
12 
TRIAL / STUDY DESIGN .................................................................................................... 12 
TRIAL / STUDY CONFIGURATION 
12 
Primary endpoint 
13 
Secondary endpoint 
13 
Safety endpoints 
13 
Stopping rules and discontinuation 
13 
RANDOMIZATION AND BLINDING 
13 
Maintenance of randomisation codes and procedures for breaking code 
14 
TRIAL/STUDY MANAGEMENT 
14 
DURATION OF THE TRIAL / STUDY AND PARTICIPANT INVOLVEMENT 
14 
End of the Trial 
14 
SELECTION AND WITHDRAWAL OF PARTICIPANTS 
14 
Recruitment 
14 
Eligibility criteria 
15 
Inclusion criteria 
15 
Exclusion criteria 
15 
Inclusion criteria 
15 
Expected duration of participant participation 
16 
Removal of participants from therapy or assessments/Participant Withdrawal 16 
Informed consent 
16 
TRIAL / STUDY TREATMENT AND REGIMEN ............................................................ 16 
Compliance 
18 
Criteria for terminating trial 
18 
TRANSPORT AND STORAGE OF THE TISSUES 
18 
LABORATORY ANALYSES 
19 
STATISTICS ........................................................................................................................... 19 
Methods 
19 
Sample size and justification 
19 
Assessment of efficacy 
20 
Assessment of safety 
20 
Procedures for missing, unused and spurious data 
20 
Definition of populations analysed 
20 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
ADVERSE EVENTS .............................................................................................................. 20 
ETHICAL AND REGULATORY ASPECTS ..................................................................... 20 
ETHICS COMMITTEE AND REGULATORY APPROVALS 
21 
INFORMED CONSENT AND PARTICIPANT INFORMATION 
21 
RECORDS 
21 
Study Forms 
21 
Sample Labelling 
22 
Source documents 
22 
Direct access to source data / documents 
22 
DATA PROTECTION 
22 
QUALITY ASSURANCE & AUDIT .................................................................................... 23 
INSURANCE AND INDEMNITY 
23 
TRIAL CONDUCT 
23 
TRIAL DATA 
23 
RECORD RETENTION AND ARCHIVING 
23 
DISCONTINUATION OF THE TRIAL BY THE SPONSOR 
24 
STATEMENT OF CONFIDENTIALITY 
24 
PUBLICATION AND DISSEMINATION POLICY .......................................................... 24 
USER AND PUBLIC INVOLVEMENT .............................................................................. 24 
STUDY FINANCES ............................................................................................................... 24 
Funding source 
24 
Participant stipends and payments 
24 
SIGNATURE PAGES ............................................................................................................ 26 
REFERENCES ....................................................................................................................... 27 
 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
TRIAL / STUDY BACKGROUND INFORMATION AND RATIONALE 
 
The Centers for Disease Control (CDC) describe vaccinations as among the 10 most 
significant health achievements ever documented [1]; and for many conditions they have been 
an unmitigated success (e.g., smallpox) [2]. There are, however, several populations in whom 
vaccine effectiveness is far from optimal. These populations are typically contending with 
underlying immune impairment by virtue of their advancing age [3] and/or the presence of co-
existing diseases (e.g., cancer). As a consequence, vaccines are most likely to fail those whom 
they most seek to benefit: individuals at the greatest risk of ill health. 
 
This has prompted research into treatments that enhance immune function prior to vaccination, 
so called vaccine adjuvants. The aim of such treatments is to optimise the response the 
immune system makes to the vaccine antigens and, in so doing, increase the likelihood that 
the vaccine confers protection.  
 
One area in which there has been interest is in the potential for developing psycho-behavioural 
vaccine adjuvants. There is considerable evidence that psychological and behavioural factors 
can modulate immunity; with diet [4], physical activity [5], stress [6], affect [7], sleep [8] and 
social support [9] all associated with immune response.   
 
We recently conducted a longitudinal observational cohort study of multiple psychological 
(positive affect, negative affect, stress) and behavioural (physical activity, sleep, diet) 
influences on short and long-term antibody responses to influenza vaccination in older 
adults. This identified positive affect as the most influential psycho-behavioural factor on 
influenza-specific antibody responses, independently predicting both short and long-term 
antibody responses in the weakest immunogenic strain above and beyond known 
demographic and clinical determinants. For example, correlations between H1N1 antibody 
response at 16 weeks post-vaccination and positive affect were r=.30, with multiple 
regression models showing positive affect explained 9.1% of additional variation in H1N1 
responses beyond age, gender and health status. Intriguingly, we also observed preliminary 
evidence that positive affect on the day of vaccination was more predictive (14% of variance 
explained) of antibody responses following vaccination than mood measured over the longer 
period surrounding vaccination. As influenza-specific antibodies are a well-established 
correlate of protection from serologically and clinically diagnosed influenza incidence [10], 
our data suggest that increasing positive affect immediately prior to vaccination could be 
used as a non-pharmacological vaccine adjuvant. 
 
In order to understand existing approaches to enhancing positive mood, we then conducted 
a systematic review of existing brief ‘mood enhancing’ interventions where immune function 
was also measured. This review identified 31 papers describing 38 single-session 
interventions that improved mood and where an aspect of immunity was measured (most 
commonly secretory IgA (SIgA) in 12/ 31 studies). Interventions were varied with the most 
common being a comedy film or audiotape (n=15/38; 39.5%) and music making in the form 
of group drumming (n=3) or singing (n=4) were also popular interventions. The remaining 
interventions included relaxation with or without immune suggestions (n=3), mental recall of 
positive autobiographical events (n=2), pleasant or memory retrieving odours (n=2), acting 
out an imagined positive experience (n=2), Qi therapy + rest (n=2), yoga (n=1), Watching 
film clips of attractive celebrities (n=1), Hugging and kissing a romantic partner (n=1), and 
writing about self-congruencies (n=1). Despite the variability in intervention approaches, all 
resulted in an enhancement in positive mood and the vast majority (27/31), in turn, 
demonstrated a corresponding improvement in immunity. The findings suggest, therefore, 
that there are multiple effective ways of improving mood in the short-term and that these 
almost always enhance immunity. However, the majority of these approaches would be 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
unsuitable for primary care because they can be time consuming, require specialist 
equipment or space or are labour-intensive. Further, very few studies in our review included 
older adults as participants. Thus, it remains unclear whether these approaches are 
appropriate in this population. 
 
To address this - through a series of systematic steps, including focus groups and interviews 
with older adults and health care professionals, we have recently developed a brief, positive 
affect intervention – designed to improve short-term mood in older adults and be deliverable 
within primary care. It is hoped this could act as a psycho-behavioural adjuvant to enhance 
poor responses to influenza vaccination in older adults. Before performing a definitive trial 
of the intervention’s effectiveness, a feasibility trial is needed for number of reasons: 
1. To assess whether our intervention can enhance positive affect (mood) 
2. To collect information regarding likely recruitment, effect sizes, and attrition rates for 
informing the necessary size of a larger definitive trial 
3. To examine the practicality and acceptability of delivering the intervention in routine 
primary care settings 
4. To explore the feasibility of obtaining outcome data on healthcare usage for a large 
scale trial (hospitalisation, GP visits for flu-like symptoms from medical records) 
 
TRIAL / STUDY OBJECTIVES AND PURPOSE 
 
PURPOSE 
The purpose of this study is to trial the feasibility of a recently developed positive affect 
intervention for older adults delivered close to the point of vaccination. 
 
PRIMARY OBJECTIVE 
 
The primary objective of this study is to assess the effects on a positive affect intervention on 
mood. The effects of the intervention on positive affect will be assessed by change from 
immediately pre- to post-intervention via self-report using validated instruments including the 
international short form of positive and negative affect scale [11]. 
 
SECONDARY OBJECTIVES 
 
 
To collect feasibility measures including recruitment rates, across study attrition, and 
missing data levels which will be recorded to inform a future definitive trial. 
 
To obtain effect size estimates for the intervention’s influence on non-specific and 
vaccine specific immunological outcomes. 
 
To understand the experiences of participants and health care professionals involved 
in conducting a trial of this nature. 
 
TRIAL / STUDY DESIGN 
 
TRIAL / STUDY CONFIGURATION 
 
Multi-centre, 2 arm parallel randomised controlled feasibility trial. After the trial, a selection of 
participants and health care professionals involved in the trial will be invited to participate in 
post-trial focus groups/interviews to inform changes needed for a larger definitive trial. 
 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
 
 
 
 
Primary endpoint 
 
The primary objective of this study is to assess the effects on a positive affect intervention on 
mood. Therefore, out primary end-point is immediately post-intervention. The primary 
outcome for analyses will be change in positive affect from pre- to immediately post-
intervention as measured by change in validated self-report measures e.g., international 
short form of the positive and negative affect scale [11]. 
 
Secondary endpoint 
 
Recruitment rates, attrition, and missing data levels up to and including 16 weeks post-
vaccination. 
Secretory IgA concentration change from pre- to immediately post-intervention. 
Antibody responses to influenza vaccination at 4 and 16 weeks post-vaccination. 
Health service utilisation (e.g., GP visits relating to upper and lower respiratory illnesses, flu-
like symptoms, antibiotic prescription, hospitalisation) assessed in medical records at 6 
months post-vaccination. 
 
Safety endpoints 
 
We do not expect any safety issues to arise from any aspects of our study. 
 
Stopping rules and discontinuation 
Discontinuation of individual participants in the study will occur if a) people indicate a wish to 
withdraw, or b) if, clinically, there are changes which mean that it would be inappropriate for 
a person to continue with the study (e.g. illness resulting in severe physical frailty or death 
which becomes apparent in the time-period between recruitment and study completion). 
 
RANDOMIZATION AND BLINDING 
 
Participants will be individually randomised on a 1:1 ratio to either the experimental or active 
control arm. The randomisation either be implemented by a software algorithm on a package 
(e.g., OpenSesame software or similar) that will be used to present questionnaires and the 
intervention/control video on a computer tablet device to participants or independently by a 
third party using an online randomization service (www.randomization.com). Randomisation 
will be implemented such that researchers are unaware of participant assignment.  
 
Participants will not be informed about the nature of each assignment and will be given the 
same instructions regardless of condition. In this regard, the participants will be blind the nature 
of the other condition. 
 
All researchers will be blinded to the participant assignment until the end of the study. 
 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
For involvement in post-trial focus groups/interviews, participants ID numbers will be entered 
into an excel database and will be randomly selected to take part using the RANDOM() 
function.  
 
Maintenance of randomisation codes and procedures for breaking code 
 
Allocations will only be identified at the end of the study. We foresee no scenarios in which 
allocations would need to be revealed at an earlier point on safety grounds. 
 
 
TRIAL/STUDY MANAGEMENT 
The Chief investigator and other members of the study team (e.g., site principle investigators) 
will be responsible for obtaining informed consent, data collection and analysis. The analysis 
will be performed by the Chief investigator with oversight from the Study Statistician.    
 
The Chief Investigator has overall responsibility for the study and shall oversee all study 
management. 
 
The data custodian will be the Chief Investigator. 
 
DURATION OF THE TRIAL / STUDY AND PARTICIPANT INVOLVEMENT 
Study Duration: Enrolment will begin in August 2017 and cease when sufficient participants 
have been recruited or January 2018 (whichever is earliest). The active part of the trial will end 
when the final participant attends their 16 week post-vaccination follow-up (anticipated 
March/April 2018). Although post-trial focus groups and examination of medical records will 
occur at up to 6 months post-vaccination. 
 
Participant Duration: 16 Weeks. Intervention will occur at baseline, prior to receipt of 
vaccination. Follow-up visits will occur at 4 weeks and 16 weeks post-vaccination. Medical 
records will be accessed at 6 months post-vaccination to examine health service utilization. 
 
End of the Trial 
The end of the active portion of the study will be the last visit of the last participant, 16 weeks 
post-vaccination. However, medical records will be examined at 6 months post-vaccination 
for all participants to examine health service utilization. 
 
 
SELECTION AND WITHDRAWAL OF PARTICIPANTS 
 
Recruitment 
Approximately 110 adults aged 65-85 years, who would normally be invited to receive the 
seasonal influenza vaccine as part of usual care, will be recruited from primary care. 
According to recent NHS information centre data, a typical medium sized practice has 
between 4000 to 7999 patients. Approximately 14% of these will be aged between 65-85 
years. A typical medium sized practice could, therefore, identify between 560 and 1120 
eligible patients; and a sample size of 110 would require 10-20% of eligible patients to 
participate. Thus, we will seek to recruit from 2 practices (to be identified with assistance of 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
clinical research network) to maximise the probability of meeting this recruitment target. If 
early recruitment levels are below expectation, a third practice may be used as an additional 
study site. 
 
Participants will be recruited from primary care clinics. The initial approach will be via invitation 
letter from the patient’s GP, and information about the study will be provided. 
 
The investigator or their nominee, e.g. from the research team or a member of the participant’s 
usual care team, will inform the participant, of all aspects pertaining to participation in the study 
if the patient expresses interest by returning a reply slip.  
 
It will be explained to the potential participant that entry into the trial is entirely voluntary and 
that their treatment and care will not be affected by their decision. It will also be explained that 
they can withdraw at any time. If the participant wishes to withdraw then they can request the 
erasure of any collected, but not yet analysed, data by contacting the chief investigator. Should 
the participant lose capacity to consent during the study they will be withdrawn from the study. 
Identifiable data or samples already collected with consent would be retained and used in the 
study. No further data or samples would be collected or any other research procedures carried 
out in relation to that participant. 
 
Eligibility criteria 
 
For Feasibility Trial: 
Inclusion criteria 
Males and Females aged 65-85 years (inclusive) 
Received influenza vaccination for the 2016/17 season 
Eligible to receive 2017/18 influenza vaccination as part of usual care 
Ability to give informed consent  
 
Exclusion criteria 
Males and Females aged less than 65 or over 85 years (exclusive) 
Did not receive influenza vaccination for the 2016/17 season 
Ineligible to receive 2017/18 influenza vaccination as part of usual care 
Unable to provide informed consent 
Deemed by health care provider to be:  
Too physically frail to participate 
Diagnosed with dementia or other cognitive condition which would make participation difficult 
Insufficient command of English language 
Influenza vaccination contraindicated 
Sufficiently impaired of hearing or vision that exposure to the intervention or control video 
content as intended would be compromised 
Those for whom the collection of blood samples is contraindicated. 
 
For Post-Trial Staff Interviews: 
Inclusion criteria 
Member of staff at a GP practice site involved in the feasibility trial 
Aware of and observed aspects of the feasibility trial at their site 
 
Exclusion criteria 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
Not staff at a GP practice site involved in the feasibility trial 
Unaware of or did not observe any aspect of the feasibility trial at their site 
 
 
Expected duration of participant participation 
Study participants will be participating in the study for 16 weeks. Although participants 
medical records will be accessed at 6 months post-vaccination to examine health care 
utilization. 
 
Removal of participants from therapy or assessments/Participant Withdrawal 
Participants may be withdrawn from the trial either at their own request or at the discretion of 
the Investigator or on the advice of their health care professional (for example on the basis of 
health or inability to continue). The participants will be made aware that this will not affect their 
future care. Participants will be made aware (via the information sheet and consent form) that 
should they withdraw the data collected to date cannot be erased and may still be used in the 
final analysis. Participant who withdraw after randomisation will not be replaced. 
 
Informed consent 
All participants will provide written informed consent. The Informed Consent Form will be 
signed and dated by the participant before they enter the trial. The Investigator will explain the 
details of the trial and provide a Participant Information Sheet, ensuring that the participant has 
sufficient time to consider participating or not. The Investigator will answer any questions that 
the participant has concerning study participation.  
 
Informed consent will be collected from each participant before they undergo any interventions  
related to the study. One copy of this will be kept by the participant, one will be kept by the 
Investigator, and a third will be retained in the patient’s medical records. 
 
Should there be any subsequent amendment to the final protocol, which might affect a 
participant’s participation in the trial, continuing consent will be obtained using an amended 
Consent form which will be signed by the participant. 
 
 
 
TRIAL / STUDY TREATMENT AND REGIMEN 
 
Study participants will: 
 
Be identified as meeting inclusion or exclusion criteria by their GP practice. Those eligible for 
participation will receive a letter from their GP, detailing the nature of the study, and inviting 
them take part. Those wishing to take part will return a reply slip, in a freepost envelope 
provided, to researchers. 
Researchers will contact participants who indicated they wanted to take part to arrange a 
time to discuss the research. Participants will be provided with an information sheet, have the 
opportunity task any questions they may have regarding the study and will provide informed 
consent if they are happy to participate. Participants expressing interest in the study and 

 
 
 
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This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
giving consent will receive and be asked to complete a short questionnaire containing 
questions to ascertain the following demographic details: 
 
Age 
 
Gender 
 
Ethnicity 
 
Education 
 
Household income 
 
Occupation 
 
Marital status 
 
Living status 
 
Smoking status 
A trait version of the positive and negative affect scale [12] and the emotional reactivity scale 
[14], the Health Status Questionnaire [16] and the Life Orientation Test – Revised [17], which 
is a measure of dispositional optimism . Participants will be asked to return this questionnaire 
in a freepost envelope or at their first GP study visit. 
First Visit to GP Surgery 
 
Participants will be randomised into one of two trial conditions (Experimental, Active Control). 
In both conditions, participants will have a pre-vaccination blood sample (approx. 8ml) taken 
via venepuncture (necessary for post-vaccine comparisons.Following this, participants will be 
asked to provide a saliva sample using the passive drool method technique before and after 
vaccination, and complete pre-intervention questionnaires to assess current mood. These 
will include the Positive and Negative Affect Scale [12], Two Visual Analogue items [13], and 
a single item mood measure developed for the present study using pictures (including older 
adult faces) to help represent mood states. 
Participants will then individually view a 15-20 minute video package on a tablet or similar 
audio/visual device. The content of the video will differ according to their random assignment.  
Experimental Condition 
Participants in the experimental condition will view a video designed to induce positive affect. 
This includes 3 short comedy clips (fork handles sketch, the two Ronnie’s; A room with a 
view – faulty towers; Tim Vine Live stand-up extract), uplifting music (Jailhouse Rock - Elvis 
Presley; Happy Together – The Turtles), jokes and positive imagery. The content of the 
intervention has been informed by patient and public involvement, focus groups with older 
adults, and pilot testing. 
The full video can be viewed at: https://youtu.be/U7QNfKOa19I 
Control Condition 
Participants in the control condition will view a video of matched length to the experimental 
condition video, but not designed to induce mood change. This includes short documentary 
clips (a pride in pencils; model railways, lecture extract on hydration), neutral music and 
images. 

 
 
 
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This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
The full video can be viewed at: https://youtu.be/h5X5mmydbEU 
After viewing their respective videos, participants will provide a second saliva sample and 
repeat the same mood assessment questionnaires as listed above. Participants will then 
receive a standard dose of the 2017/18 influenza vaccination (as part of usual care). 
Second Visit to GP Surgery (4 weeks post-vaccination) 
 
Four weeks after the first visit, participants will be asked to return to their GP surgery, where 
they will have a follow-up blood sample taken (approx. 8ml) via venepuncture.  
Third Visit to GP Surgery (16 Weeks Post-vaccination) 
 
16 weeks after the first visit, participants will be asked to return to their GP surgery, where 
they will have a follow-up blood sample taken (approx. 8ml) via venepuncture. 
Post-Trial Qualitative Interviews 
At the completion of the third visit to the GP surgery, a random selection of 20 participants 
will be invited to participate in post-trial focus groups or interviews, that will last 
approximately 1 hour, regarding the study and intervention design. Topics that will be 
addressed in the focus group include: the acceptability of the intervention, what worked and 
what didn’t work for them and whether they felt it was suitable for wider use (or if not how it 
should be changed).  
 
Separately a focus group or individual interviews (depending on availability) will be run with 
3-4 HCPs from the study site(s), however, greater emphasis will be placed on the practicality 
of intervention delivery, and barriers and facilitators to delivery.  
 
Focus groups/interviews will be recorded and analysed for common themes using thematic 
analysis in a constant comparative approach [15]. 
Compliance 
Compliance is defined as the proportion of participants that complete baseline assessments, 
observe the intervention/control video; receive influenza vaccination and attend at least one 
post-vaccination visit for blood sampling. 
 
Criteria for terminating trial 
We do not anticipate the study will be terminated early. 
 
TRANSPORT AND STORAGE OF THE TISSUES 
Samples will be stored in linked anonymised format at the place of collection and labelled 
using a combination of date of birth, initials and study number to permit accurate linkage to 
clinical data and the consent form.  
 
The master database will be held by the co-ordinating centre in a password encrypted file.  
 
Blood samples will be collected in gold-topped vacutainers (approximately 8ml). Serum will 
be isolated, aliquoted and stored at -80 degrees centigrade. The analysis of serum samples 
will take place at the University of Nottingham within the School of Life Sciences, and also at 
other authorised laboratories within the University of Nottingham. 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
 
Saliva samples (approximately 2ml) will be collected in polypropylene tubes. Saliva will be 
frozen and stored at -20 degrees centigrade. The analysis of serum samples will take place 
at the University of Northumbria, and also at other authorised laboratories within the 
University of Northumbria. 
 
Samples will be collected and transferred from the place of collection to the respective 
collaborators in batch shipments by courier as frequently as required.  All shipments will 
contain a complete inventory of all samples, along with the name of the person responsible 
for sending the samples. If participants are agreeable and sign the optional clause on the 
consent form, once analysis has taken place, samples will be placed into storage at the 
University of Nottingham. Where participants do not agree to the future use of the samples 
they will be destroyed in accordance with the Human Tissue Act, 2004.  
 
LABORATORY ANALYSES 
 
Laboratory analyses will be conducted on blood and saliva samples taken from participants.  
 
Blood Samples 
Blood Samples will be assessed for a variety of immunological parameters relevant to vaccine 
response (e.g., IgG and hemagglutination inhibiting antibody levels). They may also be 
analysed for other immunological parameters relevant to the immune and endocrine response 
to vaccination and/or mood induction (e.g., cytokines).  The analyses will be conducted by the 
Chief Investigator, overseen by co-investigators Lucy Fairclough, Paddy Tighe and Ian Todd. 
All analyses will be completed at the University of Nottingham using equipment and 
laboratories serviced and managed at the University of Nottingham.  
 
Saliva Samples 
Saliva Samples will be primarily assessed for secretory IgA. They may also be analysed for 
other immunological parameters relevant to the immune and endocrine response to 
vaccination and/or mood induction (e.g., cortisol). The analyses will be conducted by laboratory 
technicians at the University of Northumbria, overseen by co-investigator Mark Wetherell. All 
analyses will be completed at the University of Northumbria using equipment and laboratories 
serviced and managed at the University of Northumbria. 
 
STATISTICS 
 
Methods  
 
Analyses will be primarily performed by Kieran Ayling, with input from the project statistician 
(Graziella Figueredo) using SPSS and Stata software packages. 
 
While many outcomes of interest will be descriptive in nature (e.g., attrition, recruitment 
rates), between study arm comparisons will be made on a number of primary and secondary 
outcomes (positive affect, antibody response, S-IgA concentration, flu-like symptoms, health 
service utilization) using appropriate statistical tests (e.g., t-tests, ANOVA). Intention-to-treat 
analyses will be favoured where appropriate.  
 
Sample size and justification 
 

 
 
 
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This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
As a feasibility study, the sample size has been selected to inform the design of a future 
definitive RCT allowing us to examine recruitment uptake levels, attrition, intervention 
engagement, and suitability of data collection methods. It is not our aim to be powered to 
detect effects in vaccine specific outcomes (e.g., antibody responses, rates of flu like illness) 
but to provide initial effect size estimates for a future larger RCT. However, our sample size 
will be sufficient to provide adequate power to detect between pre-post differences in positive 
affect between the intervention and active control arms. Our power calculation (two-tailed 
dependent t-test difference in means) is based on the intervention demonstrating a medium 
effect size (dz=.5) on mood. A sample of 45 participants would be needed per arm to provide 
95% power to detect pre-post differences. We will, therefore, aim to recruit 55 participants 
per intervention arm to allow for attrition.  
 
Assessment of efficacy 
 
Efficacy of the intervention will be assessed by a significantly larger change in at least one of 
our positive affect measures (e.g., pre-post differences in PANAS scores) in the experimental 
condition than in the control condition.  
 
Secondary efficacy assessments will be made in relation to secretory IgA levels and 
vaccination responses however this will be to provide an effect size estimate for a future 
definitive trial – rather than an efficacy endpoint per se. 
 
Assessment of safety 
We do not expect any safety issues to arise from any aspects of our study and therefore have 
no safety endpoint per se.  
 
Procedures for missing, unused and spurious data 
Missing and spurious data will be recorded to assess relevance and usefulness of measures. 
Where deemed appropriate by the study statistician, some data may be imputed from previous 
participant or mean observations. 
 
Definition of populations analysed 
Analysis will be conducted of a full data set for all participants who are deemed to have no 
major protocol violations that could interfere with the objectives of the study. Such a set will 
comprise all participants, who complete baseline assessment (and consent form) and for 
whom post-baseline assessment of the primary outcome measure is available. 
 
 
ADVERSE EVENTS 
The occurrence of an adverse event as a result of participation is not expected. However, 
participants may experience some bruising and minor discomfort or feeling faint following 
blood sampling (usual side-effects of venepuncture). These will not be considered an 
adverse event. 
  
ETHICAL AND REGULATORY ASPECTS 
 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
ETHICS COMMITTEE AND REGULATORY APPROVALS 
The trial will not be initiated before the protocol, informed consent forms and participant and 
GP information sheets have received approval / favourable opinion from the Research Ethics 
Committee (REC), the respective National Health Service (NHS) or other healthcare provider’s 
Research & Development (R&D) department, and the Health Research Authority (HRA) if 
required. Should a protocol amendment be made that requires REC approval, the changes in 
the protocol will not be instituted until the amendment and revised informed consent forms and 
participant information sheets (if appropriate) have been reviewed and received approval / 
favourable opinion from the REC and R&D departments. A protocol amendment intended to 
eliminate an apparent immediate hazard to participants may be implemented immediately 
providing that the REC are notified as soon as possible and an approval is requested. Minor 
protocol amendments only for logistical or administrative changes may be implemented 
immediately; and the REC will be informed. 
 
The trial will be conducted in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki, 1996; the principles of Good Clinical Practice, and the Department of 
Health Research Governance Framework for Health and Social care, 2005. 
 
INFORMED CONSENT AND PARTICIPANT INFORMATION 
The process for obtaining participant informed consent will be in accordance with the REC 
guidance, and Good Clinical Practice (GCP) and any other regulatory requirements that might 
be introduced. The investigator or their nominee and the participant shall both sign and date 
the Informed Consent Form before the person can participate in the study. 
 
The participant will receive a copy of the signed and dated forms and the original will be 
retained in the Trial Master File. A second copy will be filed in the participant’s medical notes 
and a signed and dated note made in the notes that informed consent was obtained for the 
trial.  
 
The decision regarding participation in the study is entirely voluntary. The investigator or their 
nominee shall emphasize to them that consent regarding study participation may be withdrawn 
at any time without penalty or affecting the quality or quantity of their future medical care, or 
loss of benefits to which the participant is otherwise entitled. No trial-specific interventions will 
be done before informed consent has been obtained. 
 
The investigator will inform the participant of any relevant information that becomes available 
during the course of the study, and will discuss with them, whether they wish to continue with 
the study. If applicable they will be asked to sign revised consent forms. 
 
If the Informed Consent Form is amended during the study, the investigator shall follow all 
applicable regulatory requirements pertaining to approval of the amended Informed Consent 
Form by the REC and use of the amended form (including for ongoing participants). 
 
 
RECORDS  
Study Forms 
 
Each participant will be assigned a trial identity code number, allocated at randomisation if 
appropriate, for use on study forms other trial documents and the electronic database. This 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
identity code will also use a jumbled combination of their initials (of first and last names) and 
date of birth (dd/mm/yy).  
 
Study forms will be treated as confidential documents and held securely in accordance with 
regulations. The investigator will make a separate confidential record of the participant’s name, 
date of birth, local hospital number or NHS number, and Participant Trial Number (the Trial 
Recruitment Log), to permit identification of all participants enrolled in the trial, in accordance 
with regulatory requirements and for follow-up as required. Study forms shall be restricted to 
those personnel approved by the Chief or local Principal Investigator and recorded on the ‘Trial 
Delegation Log.’ 
 
All paper forms shall be filled in using black ballpoint pen. Errors shall be lined out but not 
obliterated by using correction fluid and the correction inserted, initialled and dated. 
The Chief or local Principal Investigator shall sign a declaration ensuring accuracy of data 
recorded in the study forms. 
 
Sample Labelling  
Each participant will be assigned a trial identity code number for use on the samples, consent 
forms and other study documents and the electronic database. This identity code will also use 
a jumbled combination of their initials (of first and last names) and date of birth (dd/mm/yy).  
 
Source documents  
Source documents shall be filed at the investigator’s site and may include but are not limited 
to, consent forms, current medical records, laboratory results and records. A study form may 
also completely serve as its own source data. Only trial staff as listed on the Delegation Log 
shall have access to trial documentation other than the regulatory requirements listed below. 
 
Direct access to source data / documents 
The study forms and all source documents, including progress notes and copies of laboratory 
and medical test results shall made be available at all times for review by the Chief Investigator,  
Sponsor’s designee and inspection by relevant regulatory authorities (e.g. DH, Human Tissue 
Authority). 
 
DATA PROTECTION  
All trial staff and investigators will endeavour to protect the rights of the trial’s participants to 
privacy and informed consent, and will adhere to the Data Protection Act, 1998. The study 
forms will only collect the minimum required information for the purposes of the trial. Study 
forms will be held securely, in a locked room, or locked cupboard or cabinet. Access to the 
information will be limited to the trial staff and investigators and relevant regulatory authorities 
(see above). Computer held data including the trial database will be held securely and 
password protected. All data will be stored on a secure dedicated web server. Access will be 
restricted by user identifiers and passwords (encrypted using a one way encryption method). 
Information about the trial in the participant’s medical records / hospital notes will be treated 
confidentially in the same way as all other confidential medical information. 
 
Electronic data will be backed up every 24 hours to both local and remote media in encrypted 
format. 
 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
QUALITY ASSURANCE & AUDIT  
 
INSURANCE AND INDEMNITY 
 
Insurance and indemnity for trial participants and trial staff is covered within the NHS Indemnity 
Arrangements for clinical negligence claims in the NHS, issued under cover of HSG (96)48. 
There are no special compensation arrangements, but trial participants may have recourse 
through the NHS complaints procedures. 
 
The University of Nottingham as research Sponsor indemnifies its staff, research 
participants and research protocols with both public liability insurance and clinical trials 
insurance. These policies include provision for indemnity in the event of a successful litigious 
claim for proven non-negligent harm.  
 
 
TRIAL CONDUCT 
 
Trial conduct may be subject to systems audit of the Trial Master File for inclusion of essential 
documents; permissions to conduct the trial; Trial Delegation Log; CVs of trial staff and training 
received; local document control procedures; consent procedures and recruitment logs; 
adherence to procedures defined in the protocol (e.g. inclusion / exclusion criteria, correct 
randomisation, timeliness of visits); adverse event recording and reporting; accountability of 
trial materials and equipment calibration logs. 
 
 
TRIAL DATA  
 
Monitoring of trial data shall include confirmation of informed consent; source data verification; 
data storage and data transfer procedures; local quality control checks and procedures, back-
up and disaster recovery of any local databases and validation of data manipulation. The Trial 
Coordinator/ or where required, a nominated designee of the Sponsor, shall carry out 
monitoring of trial data as an ongoing activity.  
 
Entries on study forms will be verified by inspection against the source data. A sample of study 
forms (10% or as per the study risk assessment) will be checked on a regular basis for 
verification of all entries made. In addition the subsequent capture of the data on the trial 
database will be checked. Where corrections are required these will carry a full audit trail and 
justification. 
 
Trial data and evidence of monitoring and systems audits will be made available for inspection 
by REC as required. 
 
 
RECORD RETENTION AND ARCHIVING 
In compliance with the ICH/GCP guidelines, regulations and in accordance with the University 
of Nottingham Research Code of Conduct and Research Ethics, the Chief or local Principal 
Investigator will maintain all records and documents regarding the conduct of the study. These 
will be retained for at least 7 years or for longer if required. If the responsible investigator is no 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
longer able to maintain the study records, a second person will be nominated to take over this 
responsibility.  
 
The Trial Master File and trial documents held by the Chief Investigator on behalf of the 
Sponsor shall be finally archived at secure archive facilities at the University of Nottingham.  
This archive shall include all trial databases and associated meta-data encryption codes. 
 
DISCONTINUATION OF THE TRIAL BY THE SPONSOR  
The Sponsor reserves the right to discontinue this trial at any time for failure to meet expected 
enrolment goals, for safety or any other administrative reasons.  The Sponsor shall take advice 
from the Trial Steering Committee and Data Monitoring Committee as appropriate in making 
this decision. 
 
STATEMENT OF CONFIDENTIALITY  
Individual participant medical information obtained as a result of this study are considered 
confidential and disclosure to third parties is prohibited with the exceptions noted above. 
Participant confidentiality will be further ensured by utilising identification code numbers to 
correspond to treatment data in the computer files. 
 
Such medical information may be given to the participant’s medical team and all appropriate 
medical personnel responsible for the participant’s welfare.  
 
If information is disclosed during the study that could pose a risk of harm to the participant or 
others, the researcher will discuss this with the CI and where appropriate report accordingly. 
 
Data generated as a result of this trial will be available for inspection on request by the 
participating physicians, the University of Nottingham representatives, the REC, local R&D 
Departments and the regulatory authorities. 
 
 
PUBLICATION AND DISSEMINATION POLICY 
Results from this study will be written up for publication in leading academic journals in the 
field (e.g., Brain, Behaviour and Immunity) in the year following study completion. No 
participants will be identified in these publications.  
 
 
USER AND PUBLIC INVOLVEMENT 
This study has benefited from input from patient and public involvement (Adults aged 65-85) 
whose input was sought for the purpose of the proposed study, including intervention content 
and participant documentation. We would like to thank those who participated for their advice 
and input. 
 
STUDY FINANCES 
 
Funding source  
This research is funded by the National Institute for Health Research - School for Primary 
Care Research (NIHR SPCR) 
 
Participant stipends and payments 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
Participants will receive up to £20 (£10 per non-standard visit to GP surgery) in inconvenience 
payments for participation in the study, travel and parking costs. Additionally, those participants 
who take part in the post-trial focus groups will receive a further £20 inconvenience payment. 
 
 
 

 
 
 
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Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
SIGNATURE PAGES 
 
Signatories to Protocol: 
 
Chief Investigator: (name)_____Kieran Ayling_____________________________ 
 
 
Signature:__________________________________ 
 
 
Date: ___________ 
 
 
 
 
Co- investigator: 
(name) _______Kavita Vedhara_______________________ 
 
 
Signature:__________________________________ 
 
 
Date: ___________ 
 
 
 
Trial Statistician:  (name)_____Grazziela Figueredo__________ 
 
 
Signature:__________________________________ 
 
 
Date: ___________ 
 
 
 
 
 
 
 

 
 
 
Page 27 of 27 
 
Mood and Influenza Vaccine Response: A Feasibility Trial Protocol Final 1.1 21/08/17 
 
This protocol is confidential and the property of the University of Nottingham. No part of it may be 
transmitted, reproduced, published, or used by others persons without prior written authorisation 
from the University of Nottingham 
REFERENCES 
 
1  
Global Public Health Achievements Team CDC. Ten Great Public Health 
Achievements-Worldwide, 2001-2010 (Reprinted from MMWR vol 60, pg 814-818, 
2011). JAMA 2011;306:484–7. 
2  
Andre F, Booy R, Bock H, et al. Vaccination greatly reduces disease, disability, death 
and inequity worldwide. Bull World Health Organ 2008;86:140–6. 
3  
Jefferson T, Rivetti D, Rivetti  a., et al. Efficacy and effectiveness of influenza vaccines 
in elderly people: A systematic review. Lancet 2005;366:1165–74. doi:10.1016/S0140-
6736(05)67339-4 
4  
Calder PC, Jackson A. Undernutrition, infection and immune function. Nutr Res Rev 
2000;13:3–29. doi:10.1079/095442200108728981 
5  
Simpson R, Spielmann G. Exercise and Immunosenescence. In: Bosch J, Phillips A, 
Lord J, eds. Immunosenescence. New York: : Springer Science 2013. 159–78. 
6  
Segerstrom S, Miller G. Psychological Stress and the Human Immune System: A 
Meta-Analytic Study of 30 Years of Inquiry. Psychol Bull 2004;130:601–30. 
doi:10.1037/0033-2909.130.4.601 
7  
Pressman S, Cohen S. Does Positive Affect Influence Health? Psychol Bull 
2005;131:925–71. doi:10.1037/0033-2909.131.6.925 
8  
Bryant P, Trinder J, Curtis N. Sick and tired: Does sleep have a vital role in the 
immune system? Nat Rev Immunol 2004;4:457–67. doi:10.1038/nri1369 
9  
Uchino B. Social Support and Health: A Review of Physiological Processes Potentially 
Underlying Links to Disease Outcomes. J Behav Med 2006;29:377–87. 
doi:10.1007/s10865-006-9056-5 
10  
Coudeville L, Bailleux F, Riche B, et al. Relationship between haemagglutination-
inhibiting antibody titres and clinical protection against influenza: development and 
application of a bayesian random-effects model. BMC Med Res Methodol 2010;10:18. 
doi:10.1186/1471-2288-10-18 
11  
Thompson E. Development and Validation of an Internationally Reliable Short-Form of 
the Positive and Negative Affect Schedule (PANAS). J Cross Cult Psychol 
2007;38:227–42. doi:10.1177/0022022106297301 
12  
Watson D, Clark LA, Tellegen A. Development and validation of brief measures of 
positive and negative affect: the PANAS scales. J Pers Soc Psychol 1988;54:1063–
70. doi:10.1037/0022-3514.54.6.1063 
13  
Betella A, Verschure PF. The affective slider: a digital self-assessment scale for the 
measurement of human emotions. PloS one. 2016 Feb 5;11(2):e0148037. 
14  
Nock MK, Wedig MM, Holmberg EB, et al. The Emotion Reactivity Scale: 
Development, Evaluation, and Relation to Self-Injurious Thoughts and Behaviors. 
Behav Ther 2008;39:107–16. doi:10.1016/j.beth.2007.05.005 
15  
Glaser B. The Constant Comparative Method of Qualitative Analysis. Soc Probl 
1965;12:436–45. 
16 
Radosevich D, Pruitt M. Twelve-item health status questionnaire: HSQ-12 version 2.0. 
Health Outcomes Institute. 1995. 
17 
Scheier MF, Carver CS, Bridges MW. Distinguishing optimism from neuroticism (and 
trait anxiety, self-mastery, and self-esteem): a reevaluation of the Life Orientation Test. 
Journal of personality and social psychology. 1994 Dec;67(6):1063.