Online Psychological Treatment for People With Painful HIV-related Peripheral Neuropathy (OPEN Study): Qualitative Investigation of Treatment Needs
Conditions: HIV, Peripheral Neuropathy
Sponsor: King's College London

 
 
 
 
 
   
 
 
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FULL/LONG TITLE OF THE STUDY 
Online Psychological Treatment for People with Painful HIV-related Peripheral Neuropathy (OPEN 
Study): Qualitative Investigation of Treatment Needs 
 
NCT02972606 
 
SHORT STUDY TITLE / ACRONYM 
OPEN Study: Pain management treatment needs interviews 
PROTOCOL VERSION NUMBER AND DATE 
• 
Protocol version 5.0 24 April 2017 
 
 
• 
This protocol has regard for the HRA guidance and order of content 
 
 

 
 
 
 
 
   
 
 
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RESEARCH REFERENCE NUMBERS 
 
IRAS Number: 
205949 
 
SPONSORS Number: 
Not Applicable 
 
FUNDERS Number: 
PDF-2015-08-059 
 
 

 
 
 
 
 
   
 
 
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SIGNATURE PAGE 
The undersigned confirm that the following protocol has been agreed and accepted and that the Chief 
Investigator agrees to conduct the study in compliance with the approved protocol and will adhere to 
the principles outlined in the Declaration of Helsinki, the Sponsor’s SOPs, and other regulatory 
requirement. 
I agree to ensure that the confidential information contained in this document will not be used for any 
other purpose other than the evaluation or conduct of the investigation without the prior written 
consent of the Sponsor 
I also confirm that I will make the findings of the study publically available through publication or other 
dissemination tools without any unnecessary delay and that an honest accurate and transparent 
account of the study will be given; and that any discrepancies from the study as planned in this 
protocol will be explained. 
 
 
 
 
 
 
 
 
 
 
 
Chief Investigator: 
Signature:  
...................................................................................................... 
 
Date:  
24/04/2017 
Name: (please print): Dr Whitney Scott 
......................................................................................................
 
 
 
 
 
 
 

 
 
 
 
 
   
 
 
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KEY STUDY CONTACTS 
 
Chief Investigator 
Dr Whitney Scott 
020 7188 5421 
whitney.scott@kcl.ac.uk 
Sponsor 
Mr Keith Brennan 
Director of Research Management and Innovation 
King’s College London 
Room 5.23, James Clerk Maxwell Building 
Waterloo Campus 
57 Waterloo Road 
London  SE1 8WA 
Tel: 020 7848 6391 
Email: keith.brennan@kcl.ac.uk 
Joint-sponsor(s)/co-sponsor(s)  
Not applicable. 
Funder(s) 
National Institute for Health Research 
Key Protocol Contributors 
Professor Lance McCracken 
Professor Andrew Rice 
Dr Amanda Williams 
Committees 
Not applicable.  
 
 
 
 

 
 
 
 
 
   
 
 
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STUDY SUMMARY 
Study Title 
Online Psychological Treatment for People with Painful HIV-
related Peripheral Neuropathy (OPEN Study): Qualitative 
Investigation of Treatment Needs 
Internal ref. no. (or short title) 
OPEN Study: Pain management treatment needs interviews 
Study Design 
Qualitative Semi-Structured Interviews 
Study Participants 
Individuals living with HIV and chronic painful peripheral 
sensory neuropathy. 
Planned Size of Sample (if applicable) Approximately 30 participants.  
Follow up duration (if applicable) 
Not applicable. 
Planned Study Period 
November 2016 to August 2017 
Research Question/Aim(s) 
 
To investigate the needs of people with HIV and painful 
sensory neuropathy for a psychological treatment to reduce 
the impact of pain on quality of life. To explore the 
acceptability of an internet-delivered psychological 
intervention and to tailor the content and delivery format of 
the intervention to the identified needs of this group. 
 
 
 
 
 
 
 

 
 
 
 
 
   
 
 
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FUNDING AND SUPPORT IN KIND 
FUNDER(S) 
(Names and contact details of ALL organisations 
providing funding and/or support in kind for this 
study) 
FINANCIAL AND NON FINANCIALSUPPORT 
GIVEN 
National Institute for Health Research 
Financial (salary costs of the CI, and training and 
research costs) 
 
 
 
 
 
 
 
 

 
 
 
 
 
   
 
 
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ROLE OF STUDY SPONSOR AND FUNDER 
 
The lead sponsor, King's College London, will take primary responsibility for ensuring that the design 
of the study meets appropriate standards and that arrangements are in place to ensure appropriate 
conduct and reporting. King's College London also provides cover under its No Fault Compensation 
Insurance, which provides for payment of damages or compensation in respect of any claim made by 
a research subject for bodily injury arising out of participation in a clinical trial or healthy volunteer 
study (with certain restrictions).  
The funder reviewed and approved the study in the process of the Chief Investigator’s fellowship 
application. The Chief investigator must notify the funder of any publication at the time of submission 
or at least 28 days prior to publication. 
 
 
 

 
 
 
 
 
   
 
 
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ROLES AND RESPONSIBILITIES OF STUDY MANAGEMENT COMMITEES/GROUPS & 
INDIVIDUALS 
The study steering group will consist of Dr Whitney Scott, Professor Lance McCracken, Professor 
Andrew Rice, Dr Amanda Williams, and two patient representatives, Paul Clift and Paul Decle. The 
steering group will ensure that the study adheres to the protocol, and meets recruitment, data 
analysis, and dissemination objectives. Dr Whitney Scott will oversee the day-to-day management of 
the study. 
 
Protocol contributors 
Dr Whitney Scott drafted the protocol in collaboration with Professors Lance McCracken and Andrew 
Rice, and Dr Amanda Williams. Two patient representatives (Paul Decle and Paul Clift) provided input 
on the recruitment strategy, questionnaires and interview schedule, and participant information sheet 
and consent form. Another HIV patient organization (UKCAB) provided feedback on patient-facing 
study documents.  
 
KEY WORDS: 
HIV, pain, peripheral neuropathy, psychological treatment, 
qualitative research 
 

 
 
 
 
 
   
 
 
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LIST of CONTENTS 
GENERAL INFORMATION 
Page No. 
TITLE PAGE  
1 
RESEARCH REFERENCE NUMBERS 
 
2 
SIGNATURE PAGE 
3 
KEY STUDY CONTACTS 
 
4 
STUDY SUMMARY  
5 
FUNDING 
 
 
6 
ROLE OF SPONSOR AND FUNDER 
7 
ROLES & RESPONSIBILITIES OF STUDY STEERING GROUPS AND INDIVIDUALS   
8 
LIST of CONTENTS  
9 
STUDY FLOW CHART 
 
10 
SECTION  
1. BACKGROUND 
 
11-12 
2. RATIONALE 
 
11-12 
3. THEORETICAL FRAMEWORK 
12 
4. RESEARCH QUESTION/AIM(S)  
12 
5. STUDY DESIGN/METHODS 
13-14 
6. STUDY SETTING 
15 
7. SAMPLE AND RECRUITMENT 
15-17 
8. ETHICAL AND REGULATORY COMPLIANCE 
17-20 
9. DISSEMINATION  POLICY 
20 
10. REFERENCES 
21-23 
11. APPENDICIES 
N/A 
 
 
 

 
 
 
 
 
   
 
 
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STUDY FLOW CHART 
Table 1. Timeline of Study Activities 
Month 
Nov 
‘16 
Dec 
‘16 
Jan 
‘17 
Feb 
‘17 
Mar 
‘17 
Apr 
‘17 
May 
‘17 
Jun 
‘17 
July 
‘17 
Aug 
‘17 
Sept 
‘17 
Recruitment/ 
screening 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Informed 
consent, 
questionnaire 
and interview 
completion 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Transcribing 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Data Analysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Dissemination  
 
 
 
 
 
 
 
X 
X 
X 
 
 

 
 
 
 
 
   
 
 
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STUDY PROTOCOL 
OPEN Study: Pain management treatment needs interview 
 
1 and 2: BACKGROUND and RATIONALE 
The human immunodeficiency virus (HIV) remains a significant global health concern. An 
estimated 35 million people are infected with HIV worldwide (1, 2); approximately 110,000 infected 
individuals are in the United Kingdom (3). Antiretroviral therapies have significantly improved survival 
rates. At the same time, approximately 6,000 individuals are newly infected with HIV in the UK each 
year (3). Consequently, the prevalence of infected individuals is growing.  
In well-resourced countries, the shift in HIV from a terminal illness to a chronic condition has 
contributed to a greater focus on disease and symptom management (4). Pain in the feet is one of the 
most predominant symptoms associated with HIV infection and treatment. Approximately 40 to 60% 
of people with HIV have peripheral sensory neuropathy (HIV-SN); 50-90% of these experience 
neuropathic pain (5-7).  
Painful HIV-SN is associated with increased disability in daily activities, unemployment, and 
reduced quality of life (8).  Additionally, painful HIV-SN is associated with numerous comorbidities, 
including depression, panic disorder, post-traumatic stress disorder, and substance abuse (9-13). 
Thus, untreated painful HIV-SN may contribute to significant individual, societal, and economic 
burden. 
Presently, there are few options for medically managing painful HIV-SN. A systematic review of 
19 randomized controlled trials (RCTs) of pharmacological treatments for painful HIV-SN indicated 
that efficacy was found only for topical capsacin, smoked cannabis, and subcutaneous nerve growth 
factor; however, only capsaicin is clinically feasible (14). Additional negative RCTs of pregabalin and 
capsaicin have since been published (15, 16). It has been concluded that there is an ‘urgent need’ to 
evaluate novel strategies to manage painful HIV-SN (14).  
Psychological treatments, including Cognitive Behavioural Therapy (CBT), represent a 
potentially viable addition to the treatment of painful HIV-SN. In meta-analyses, CBT is associated 
with improved pain, function, and depression among individuals with chronic pain that is primarily 
musculoskeletal in origin (17). The development of accessible and cost-effective Internet-
administrations of CBT for pain is another promising development in this area (18).  
Within the broad category of CBT, Acceptance and Commitment Therapy (ACT) is a more 
recent treatment technology with growing support for individuals with chronic musculoskeletal pain. 
There are now 11 RCTs and numerous effectiveness studies supporting the efficacy and effectiveness 
of ACT for long-term improvements in pain, function, distress, and healthcare utilization (19, 20). ACT 
is a particularly promising innovation given its explicit theoretical basis—the psychological flexibility 
model. This model provides a unifying framework for targeting processes of change, evaluating 
treatment mechanisms and, ultimately, refining treatment (21). Additionally, the psychological 

 
 
 
 
 
   
 
 
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flexibility model and ACT are transdiagnostic, with applicability and demonstrated efficacy across a 
wide range of health conditions (22-24). Indeed, preliminary findings suggest an association between 
pain acceptance and improved HIV-related pain outcomes (25). 
  
Despite advancements in research on CBT and ACT for musculoskeletal pain conditions, 
comparable research does not exist for individuals with painful HIV-SN. One systematic review of CBT 
for neuropathic pain identified only 3 RCTs (26).  Only one of these RCTs focussed on HIV-related pain; 
this study had an unacceptably high dropout rate of 57% (27). Two additional observational cohort 
studies of group-based CBT for HIV-related pain showed similarly poor adherence (28, 29). There is a 
clear need for improving psychological interventions for individuals with HIV-related pain. Patient 
representatives and clinicians practicing in the area of HIV and pain management have been 
consulted with respect to this issue and have identified the need for better development and 
implementation of psychological treatments for pain in this population. 
 
Improving psychological treatments for painful HIV-SN will likely require greater consideration 
of the psychosocial complexities associated with this condition. For example, HIV is most common 
among gay men, women, ethnic minorities, and intravenous drug users (3, 30). There is recognition of 
important healthcare disparities and under treatment of pain in these groups (31-33). However, the 
unique perspectives and needs of individuals in these groups are not typically incorporated into 
psychologically-based pain management interventions such as CBT/ACT. Moreover, findings from the 
available qualitative literature suggest that social stigma and interpersonal distrust may influence 
treatment engagement among individuals with HIV (34-38). However, research is needed to 
understand how these psychosocial issues can best be addressed within CBT/ACT for pain.   
 
This study will use in-depth interviews to examine the needs of people with painful HIV-SN for 
a psychologically-based pain management treatment that may be delivered over the Internet. 
Interview questions will examine the impact of pain on people’s lives and how they cope with pain, 
and participants’ treatment needs in terms of treatment content and delivery format. Men, women, 
ethnic minorities, and people who use recreational drugs will be purposively sampled to ensure that 
interview responses reflect the views of people most commonly suffering from this condition.  
 
3 
THEORETICAL FRAMEWORK 
Broadly speaking, the study is framed within a biopsychosocial understanding of the experience of 
chronic pain. The purpose of the study is to understand, from the perspective of people living with 
HIV-related painful peripheral neuropathy, people’s needs for and views about a psychological 
approach to pain management delivered over the internet. As such, data collection and analysis will 
follow a grounded theory approach. Following this approach, meanings and themes that emerge from 
the interviews will be used to develop a conceptual understanding of participants’ experiences of pain 
and their views about a new pain management intervention.  
 

 
 
 
 
 
   
 
 
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4 
RESEARCH QUESTION/AIM(S) 
4.1 
Objectives 
 
The purpose of this study is to explore the needs of people with painful HIV-SN for a psychologically-
based treatment for managing chronic pain. 
4.2 
Outcome 
The interview responses will be used to develop and tailor an internet-delivered version of ACT for 
people with painful HIV-SN. Once developed, the new treatment will be tested in a feasibility trial 
(another study). It is hoped that tailoring the online ACT treatment based on the qualitative interview 
responses will increase the acceptability of the treatment and will improve treatment adherence 
rates. 
 
5 
STUDY DESIGN and METHODS of DATA COLLECTION AND DATA ANALYIS 
Participants will complete semi-structured interviews. Prior to the in-depth interview, participants will 
complete a questionnaire package at home to bring to their interview appointment (20-30 minutes to 
complete). The questionnaire package will consist of demographic and medical history questions, and 
symptom and functioning questionnaires. Individual in-depth semi-structured interviews will be 
conducted given the potentially sensitive nature of the questions and to maintain participants’ 
anonymity. Participants will be given the choice to complete the interviews at the Imperial College 
London campus of Chelsea & Westminster Hospital or Guy’s Hospital Campus of King’s College 
London, according to their preference.  
At the beginning of the interview appointment, the interviewer will conduct a 5 minute clinical 
examination to assess of symptoms and signs related to peripheral neuropathy. In the event that 
questionnaires are not completed prior to the interview session, participants will be asked to 
complete the questions at the interview appointment or at home and to mail them back in within 2 
weeks. Participants who have not completed the questionnaires 3 weeks after the interview will 
receive a telephone reminder.  
 
Pre-Interview Questionnaires 
Demographic, Medical History, and Internet Use Questions: Participants will be asked to report on the 
following demographic and medical history questions: age, gender, ethnicity, sexual orientation, 
education, employment status, living situation, date of HIV diagnosis, history of and current 
antiretroviral treatment, duration of foot pain, other chronic pain diagnoses, mental health diagnoses, 
current pain medications, current alcohol and drug use, and frequency of Internet use. 
Pain intensity and interference: The Brief Pain Inventory (BPI) will be used to assess pain intensity and 
the interference of pain with daily functioning in seven domains: general activity, mood, 

 
 
 
 
 
   
 
 
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walkingability, relations with others, sleep and enjoyment of life. The BPI has been shown to be a 
reliable and valid measure for use with people with neuropathic pain conditions, including peripheral 
neuropathy (39). Participants will also be asked to fill in a body map to indicate where they feel pain. 
Neuropathic Pain Interview: The 7-item DN4-i (Douleur Neuropathique 4-interview, English version) 
interview (questionnaire version) will be conducted to identify the probability that the participant has 
neuropathic pain. A score of ≥3 out of 7 reflects a positive diagnosis of neuropathic pain (40) (41). 
Patient Health Questionnaire (PHQ-9): The PHQ-9 (42) is a 10-item measure of the severity of 
depression symptoms based on the DSM-IV diagnostic criteria for depression. Each item is rated on a 
four point scale between 0 (not at all) and 3 (nearly every day). The PHQ-9 has shown reliability and 
validity as a measure of depressive symptoms and is commonly used as an outcome measure in 
studies of patients with chronic pain (42). 
 
Interview Appointment 
Assessment of neuropathy signs and symptoms 
The Clinical HIV-associated Neuropathy Tool screening tool (12) will be administered at the 
beginning of the interview appointment (5 minutes). This 4-item tool comprises two subjective 
symptom questions (self-report of foot pain and foot numbness), and two objective signs on clinical 
examination (loss of vibration sense and loss of ankle reflex). Clinical examination of these signs does 
not require specialist medical training. Based on a previous study using the CHANT, patients are 
considered to have peripheral neuropathy if they are positive for one symptom and one sign in a 
bilateral distribution (43). Previous data indicate that the CHANT has 100% sensitivity and 85% 
specificity for diagnosing HIV-SN in a London-based sample in relation to a more comprehensive 
neurological examination (The Utah Early Neuropathy Score) as the reference standard (43). 
Information from the physical examination of the CHANT will be used to further support the case 
definition of peripheral neuropathy from the telephone screening. However, findings of positive signs 
from the physical examination are not a requirement for study inclusion and all participants will 
proceed to the semi-structured interview. 
Semi-structured interview 
The interview schedule was developed on the basis of previous qualitative studies on 
psychological factors and treatments for pain in general and specifically in people with HIV (44, 45) 
and online CBT for pain management (46), and patient input. Participants will first be asked general 
questions about the impact of pain on their lives and how they currently cope with pain. They will also 
be asked more specific questions about their thoughts about an online psychological treatment for 
managing pain. While an interview schedule has been developed for the study, we expect questions 
to be further developed and revised during the study as data and themes emerge that require further 
probing. 

 
 
 
 
 
   
 
 
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Dr Whitney Scott will conduct the interviews, which are expected to take approximately 1 
hour each. Field notes will be made during/immediately after the interview to record the 
interviewer’s impression of the participant’s responses and the interview process. All interviews will 
be recorded using a dictaphone, transferred to a password-protected computer, and anonymised by 
Dr Whitney Scott. Dr Whitney Scott and a Bachelor’s level (or higher) student or volunteer will 
transcribe the anonymized audio recordings verbatim.  
Thematic analysis will be used to analyse the data following the recommendations of Braun 
and Clark (2006): Each transcript will be read in its entirety several times to establish familiarity. First 
level-descriptive codes will be annotated in the margin of the transcript. Second level codes will be 
used to summarize the most significant/frequent first-level codes; third-level codes will be used to 
identify higher order themes around which lower order themes are integrated. Quotes reflecting 
second-level themes will be extracted to demonstrate second-level themes for the final report (47). 
The NVivo 11.0  software program will be used to assist in data analysis. This process will be initially 
conducted by one coder; two additional coders will code 10% of the transcripts to establish the 
validity of the codes. Validity will also be established through use of the constant comparative 
method whereby the transcripts will repeatedly be reviewed to check that identified 2nd and 3rd level 
themes correspond to the data.  
 
6 
STUDY SETTING 
Participants will primarily be recruited from St Stephen’s Centre at Chelsea and Westminster Hospital 
and affiliated HIV and pain clinics in London. St. Stephen’s Centre is one of the largest HIV centres in 
Europe. Recruiting participants from Chelsea and Westminster Hospital NHS Trust will ensure 
participants recruited into the study are representative of the population of interest.  
  
7 
SAMPLE AND RECRUITMENT 
7.1  
Eligibility Criteria 
7.1.1 Inclusion criteria  
• Adults aged 18 years or older. 
• Living with HIV. 
• A positive screen for peripheral sensory neuropathy, as indicated by: presence of self-reported 
bilateral foot pain and/or numbness in a symmetrical distribution (43). 
 
• Positive screen for symptoms of neuropathic pain in the feet, as indicated by a score of >3 on 
the patient reported outcomes section of the Neuropathic Pain Interview, which has 

 
 
 
 
 
   
 
 
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previously been shown to have greater than 80% sensitivity and specificity for identifying 
people with neuropathic pain conditions (48, 49) 
• Pain in the feet present most days for at least 3 months. 
• Average pain intensity of >4 on a scale from 0 (no pain) to 10 (pain as bad as you can 
imagine)(50). 
• Average interference of pain with daily activities is >4 on scale ranging from 0 (no interference) to 
10 (unable to carry on any activities) (51). 
 
7.1.2 Exclusion criteria  
• Presence of excessive alcohol consumption, hypothyroidism, vitamin B12 deficiency, 
diabetes, exposure to isoniazid or chemotherapy drug treatment, or a known history of a 
neuropathy due to a cause other than HIV or antiretroviral treatment (12, 52) 
• Unable to conduct interview in English. 
• Current diagnosis of dementia or learning disability. 
• Unwilling to provide written informed consent. 
 
7.2  
Sampling 
7.2.1  Size of sample 
Approximately 30 participants will be recruited, with roughly equal representation of men, women, 
ethnic minorities, and people who use recreational drugs. Recruitment will terminate once saturation 
of themes has been achieved. Thus, while an approximate sample size has been estimated on the 
basis of convention in qualitative methods and the range of demographic characteristics being sought 
(53, 54), an exact sample size cannot be determined a priori.  
 
7.2.2  Sampling technique 
Men and women, ethnic minorities, and people who use recreational drugs will be purposively 
sampled through HIV and pain clinics and community organizations and through chain referral 
sampling. Purposive sampling across participants with the range of demographic backgrounds 
identified will ensure that the interview responses are reflective of people with painful HIV-SN who 
might ultimately be referred to and receive the psychologically-based pain management treatment 
being developed.  
 

 
 
 
 
 
   
 
 
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7.3 
 Recruitment 
7.3.1 Sample identification 
Participants will be recruited from St Stephens Centre at Chelsea and Westminster Hospital 
NHS Trust and associated HIV and chronic pain clinics in London (e.g., Kobler Day Care Unit, John 
Hunter Clinic, Dean Street Clinic, and the 10 Hammersmith Broadway Clinic). Consultants at these 
clinics will identify potentially eligible participants in the course of their routine clinical care and will 
ask patients for permission to give their name and contact information to the study coordinator (Dr 
Whitney Scott). For patients who agree to this, the study coordinator will conduct eligibility screening 
either in person at the clinic or over the telephone. We will also post recruitment advertisements in 
the waiting areas of these clinics which will instruct interested patients to contact the study 
coordinator directly to discuss the study and conduct eligibility screening. 
 Patients with HIV and painful peripheral neuropathy that have participated in a previous study 
at Chelsea and Westminster Hospital (the HIV-POGO Study) who have explicitly consented to be re-
contacted for future studies will also be contacted to ask to inform them of the current study. A 
member of the research team from the HIV-POGO study will provide Dr Whitney Scott with the 
contact information of individuals who have previously consented to be contacted for future studies. 
Dr Whitney Scott will then contact these individuals by letter and telephone to provide information 
about the study and conduct eligibility screening.  
Recruitment advertisements will also be sent to local HIV community groups to post in their 
centres and on their websites and social media accounts. Advertisements posted with these groups 
will ask potentially eligible and interested people to contact the study coordinator for further 
information and screening. Recruitment advertisements will likewise be posted on social media 
accounts for the study (e.g., Twitter). Lastly, eligible participants will be asked to give recruitment 
flyers to other potentially eligible individuals from their social network. Chain referral sampling is 
often used in qualitative research to recruit minority and stigmatized groups that are difficult to 
access (55).  
In the recruitment process, potential participants will be informed that they will receive a £20 
voucher and travel expenses up to £15. 
 
7.2.2 Consent 
Following screening, the study coordinator will review the participant information sheet with 
eligible participants either in person or over the telephone to describe the nature and objectives of 
the study and possible risks. Potential participants will be given the opportunity to ask the researcher 
any questions at this time. Potential participants will be given up to 1 month to consider the 
information and to decide whether they want to participant or not. Eligible individuals will be mailed 
a copy of the information sheet along with two copies of the consent form, and the pre-interview 

 
 
 
 
 
   
 
 
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questionnaires. Participants will be asked to bring the completed consent form to their interview 
appointment. The right to refuse to participate without giving a reason will be respected. We will 
emphasize that participants are free to withdraw at any time without consequence. 
8 
ETHICAL AND REGULATORY CONSIDERATIONS 
8.1 
Assessment and management of risk 
Participants’ involvement in the study will contribute to further developments in psychological 
treatments for people with painful HIV-related peripheral neuropathy. Participants will receive a gift 
voucher as compensation for their time. We cannot guarantee any further benefits to participants for 
their involvement in the study. 
Adverse events arising from this observational study are expected to be rare. However, it is 
possible that participants could become distressed in the course of the interview given the potentially 
sensitive nature of the questions. Dr Scott will debrief participants about any distress that comes up in 
the interviews. The interviewer, Dr Whitney Scott, is a registered clinical psychologist and will remain 
sensitive to this issue. All participants will be informed of their right to stop the interview at any time 
and that information will be kept strictly confidential. Participants can request to withdraw parts or all 
of their data.  
We will write a letter to the GP to inform him/her of the participant’s involvement in the 
study. Participants who score 10-14 on the PHQ-9 will be made aware of their score and will be 
recommended to contact their GP if they are concerned about this. Participants who score 15 or 
greater on the PHQ-9 will be informed of this, and will be told that Dr Scott will directly contact their 
GP to discuss this. A similar procedure will be followed if we discover any other symptoms that might 
pose a risk to a participant’s health or well-being during the course of the interview appointment.  
 
8.2  
Research Ethics Committee (REC) review & reports 
NHS REC approval will be obtained prior to beginning the study. Substantial amendments will not be 
implemented prior to REC approval. All correspondence with the REC will be retained. The Chief 
Investigator will submit an annual report as required, and will notify the REC of the end of the study 
and will submit a final report. 
 
8.3  
Peer review 
This study was reviewed by the National Institute for Health Research in the process of reviewing a 
fellowship application that was awarded to Dr Whitney Scott. Two independent, expert reviewers 
reviewed the study as part of this fellowship application.  
 

 
 
 
 
 
   
 
 
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8.4  
Patient & Public Involvement 
Paul Decle and Paul Clift are patient representatives located at St. Stephen’s Centre at Chelsea and 
Westminster Hospital and at King’s College Hospital, respectively. Paul and Paul were consulted about 
the study during the application for funding of a fellowship to undertake a larger project to develop 
and test the feasibility of an online psychologically-based pain management treatment for people 
with painful HIV-SN. Both Paul and Paul were enthusiastic about the potential benefits of the new 
treatment, but identified patient engagement as an important issue. This input solidified the need to 
incorporate a qualitative study of barriers to patient engagement for the proposed online treatment, 
which will feed into further treatment development. 
 
The patient representatives were involved in the design of the research in several ways. Paul Clift 
suggested that a multi-pronged recruitment strategy was the most appropriate to ensure we capture 
the views of the diversity of people with painful HIV-SN. This informed our recruitment strategy. Paul 
Decle did not feel that peer/patient interviewers for the qualitative study were appropriate, and, 
therefore, it was decided that a researcher (Dr Whitney Scott) would conduct the interviews. Paul 
Decle also suggested suitable remuneration (e.g., vouchers) for participants in the interview study. 
Paul and Paul reviewed study documents (e.g., recruitment adverts, information sheet, consent form, 
questionnaires, and interview schedule) and made several suggestions for re-wording, which were 
incorporated into the current version of the documents. UKCAB, which is an advocacy group of people 
living with HIV, also provided feedback on the study documents, which was also incorporated.  
 
Paul and Paul will be consulted to provide input on the themes coded from the transcribed interviews 
to ensure their relevance and appropriateness. Paul and Paul will also review a study report that will 
be given to patients following completion for the study to ensure its comprehensibility and sensitivity.  
 
8.5 
Regulatory Compliance  
The Chief Investigator will ensure that the study is conducted in compliance with the principles of the 
Declaration of Helsinki (1996), and in accordance with all applicable regulatory requirements including 
the Research Governance Framework. The Chief Investigator will ensure that NHS Research and 
Development (R&D) permission has been granted from the relevant site prior to beginning research at 
those sites. The project is eligible for inclusion in the NIHR Clinical Research Network portfolio and 
this will be applied for via the IRAS system. 
8.6  
Protocol compliance  
Any serious breaches from the approved protocol will be documented by the Chief Investigator and 
reported to the Sponsor immediately.  
8.7 
Data protection and patient confidentiality  

 
 
 
 
 
   
 
 
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All investigators will comply with the requirements of the Data Protection Act 1998 with regards to 
the collection, storage, processing and disclosure of personal information.  
For patients recruited from Chelsea and Westminster Hospital (C&W), or participants recruited from 
the community who complete study procedures at C&W, participant identifying information will be 
stored on a secure NHS computer at C&W along with the anonymization log. Paper copies of consent 
forms will be stored in a locked filing cabinet in a locked room at C&W. All participants will be given 
an anonymous study identification number that will be used for screening, questionnaires, audio files 
and transcripts, so no identifiable information will be linked with these data. Anonymous 
questionnaire data will initially be collected on paper case report forms (CRF), which will be stored in 
a locked filing cabinet in a locked room at C&W. Data from paper CRFs will subsequently be entered in 
an electronic database stored on a secure computer.  
Interviews will be recorded using a password protected dictaphone. The audio recording of interviews 
will be uploaded to a secure computer and any interview responses that identify the participant will 
be removed. Audio recordings will be erased from the dictaphone after being transferred to the 
computer. The anonymized audio files and questionnaire database will be transferred to a secure 
King’s College London computer for analysis using an encrypted USB stick.  
The identifying data of participants recruited from community organizations who complete study 
procedures at King’s College London will be stored on a secure King’s College London (KCL) computer 
at Guy’s Hospital. Hard copies of consent forms will be stored in a locked filing cabinet in a secure 
room at KCL. Paper copies of anonymized questionnaires will likewise be stored in a locked filing 
cabinet in a secure room at KCL. The anonymized electronic questionnaire database, audio files and 
transcripts will be stored on a secure KCL computer. All audio files will be destroyed after they have 
been transcribed.  
Only researchers associated with the study (from King’s College London, Imperial College London, and 
University College London), the two patient representatives, and the study sponsor (King’s College 
London) will have access to the data for the purpose of carrying out the research as described and 
monitoring the quality of the research. Dr Whitney Scott will be the custodian of the data. Data will be 
securely kept for 10 years following completion of the study. 
8.8 
Indemnity 
King’s College London will serve as the sponsor for the study and will provide indemnity for any harm 
to participants arising from the research.  
 
8.9 
Amendments  

 
 
 
 
 
   
 
 
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The Chief Investigator will decide whether amendments are substantial or non-substantial. For all 
amendments, Dr Whitney Scott will notify the study sponsor, NHS REC, and the Research and 
Development teams at all study sites. Substantial amendments will be submitted via IRAS to the lead 
CRN. No amendment will be implemented prior to approval from sponsor, REC, and R&D. A study 
document list will be used to track the most recent versions of the protocol and other study documents.  
 
8.10 
Access to the final study dataset 
Dr Whitney Scott, Professors Lance McCracken and Andrew Rice, Dr Amanda Williams, Paul Clift and 
Paul Decle will have access to the final anonymized study dataset. A Bachelor’s-level (or higher) 
student (not yet identified) may also have access to the anonymous dataset as part of his/her thesis 
project. Only Dr Whitney Scott will have access to the anonymization log that contains participant 
identifiable information. 
 
9 
DISSEMINIATION POLICY 
9.1  
Dissemination policy 
King’s College London will own the data arising from the study. The study protocol will be made 
publicly available through registration with clinicaltrials.gov prior to commencing study recruitment. 
Following completion of the study and data analysis, the study will be written up for submission for 
conference presentations and publication in peer-reviewed journals; published journal articles which 
will be made available through open-access where possible. NIHR will be acknowledged as the funder 
of the study in all publications. NIHR will be notified at the time of submission of any publication (oral 
or written) or 28 days prior to the intended publication date, whichever is earlier (according to the 
funding agreement). Anonymized data will also be presented community dissemination events (e.g., 
at meetings of relevant patient groups). A newsletter drafted in collaboration with Paul Clift and Paul 
Decle will be sent to participants to notify them of the study results and posted on the study website. 
A study newsletter will also be sent to clinicians working in the area of HIV and chronic pain. 
 
9.2  
Authorship eligibility guidelines and any intended use of professional writers 
All listed contributors to this protocol are expected to gain authorship on any publication arising from 
this study. The following criteria will determine eligibility for authorship as per the International 
Committee of Medical Journal Editors: ‘Substantial contributions to the study conception or design of the 
work, or data acquisition, analysis, or interpretation; contributing to the manuscript draft and revisions, 
and approving the final draft; and, agreement to be accountable for all aspects of the work.’ 

 
 
 
 
 
   
 
 
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10 
REFERENCES 
 
1. 
WHO. Global Health Observatory, People living with HIV/AIDS 2014 [cited 2014 November]. 
Available from: http://www.who.int/gho/hiv/en/. 
2. 
UNAIDS. World AIDS Day 2014 - Fact sheet 2014. Available from: 
http://www.unaids.org/en/WAD2014factsheet. 
3. 
NAT. People living with HIV in the UK 2014 [November 2014]. Available from: 
http://www.nat.org.uk/HIV-Facts/Statistics/Latest-UK-statistics/People-with-HIV-in-UK.aspx. 
4. 
Mahungu TW, Rodger AJ, Johnson MA. HIV as a chronic disease. Clin Med (Northfield Il). 
2009;9(2):125-8. 
5. 
Kamerman PR, Wadley AL, Cherry CL. HIV-associated sensory neuropathy: risk factors and 
genetics. Current pain and headache reports. 2012;16(3):226-36. 
6. 
Cherry CL, Kamerman PR, Bennett DL, Rice AS. HIV-associated sensory neuropathy: still a 
problem in the post-stavudine era? Future Virol. 2012;7(9):849-54. 
7. 
Cherry CL, Wadley AL, Kamerman PR. Painful HIV-associated sensory neuropathy. Pain 
management. 2012;2(6):543-52. 
8. 
Ellis RJ, Rosario D, Clifford DB, McArthur JC, Simpson D, Alexander T, et al. Continued high 
prevalence and adverse clinical impact of human immunodeficiency virus–associated sensory 
neuropathy in the era of combination antiretroviral therapy: the CHARTER Study. Arch Neurol. 
2010;67(5):552-8. 
9. 
Tsao JC, Dobalian A, Naliboff BD. Panic disorder and pain in a national sample of persons 
living with HIV. Pain. 2004;109(1):172-80. 
10. 
Tsao JC, Soto T. Pain in persons living with HIV and comorbid psychological and substance 
use disorders. The Clinical journal of pain. 2009;25(4):307. 
11. 
Tsao JC, Stein JA, Ostrow D, Stall RD, Plankey MW. The mediating role of pain in substance 
use and depressive symptoms among Multicenter AIDS Cohort Study (MACS) participants. Pain. 
2011;152(12):2757-64. 
12. 
Phillips TJ, Brown M, Ramirez JD, Perkins J, Woldeamanuel YW, Williams ACdC, et al. 
Sensory, psychological, and metabolic dysfunction in HIV-associated peripheral neuropathy: a cross-
sectional deep profiling study. Pain. 2014;155(9):1846-60. 
13. 
Merlin JS, Cen L, Praestgaard A, Turner M, Obando A, Alpert C, et al. Pain and physical and 
psychological symptoms in ambulatory HIV patients in the current treatment era. J Pain Symptom 
Manage. 2012;43(3):638-45. 
14. 
Phillips TJ, Cherry CL, Cox S, Marshall SJ, Rice AS. Pharmacological treatment of painful HIV-
associated sensory neuropathy: a systematic review and meta-analysis of randomised controlled 
trials. PLoS One. 2010;5(12):e14433. 
15. 
Clifford DB, Simpson DM, Brown S, Moyle G, Brew BJ, Conway B, et al. A randomized, 
double-blind, controlled study of NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful 
HIV-associated distal sensory polyneuropathy. JAIDS Journal of Acquired Immune Deficiency 
Syndromes. 2012;59(2):126-33. 
16. 
Simpson DM, Rice AS, Emir B, Landen J, Semel D, Chew ML, et al. A randomized, double-
blind, placebo-controlled trial and open-label extension study to evaluate the efficacy and safety of 
pregabalin in the treatment of neuropathic pain associated with human immunodeficiency virus 
neuropathy. Pain. 2014;155(10):1943–54. 

 
 
 
 
 
   
 
 
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OPEN Study: Pain management treatment needs interviews 23 
 
            
 
 
                                        
17. 
Williams A, Eccleston C, Morley S. Psychological therapies for the management of chronic 
pain (excluding headache) in adults. Cochrane Database Syst Rev. 2012;11. 
18. 
Eccleston C, Fisher E, Craig L, Duggan GB, Rosser BA, Keogh E. Psychological therapies 
(Internet-delivered) for the management of chronic pain in adults. The Cochrane Library. 2014(2). 
19. 
Veehof M, Oskam M, Schreurs K, Bohlmeijer E. Acceptance-based interventions for the 
treatment of chronic pain: A systematic review and meta-analysis. Pain. 2011;152(3):533-42. 
20. 
Hann KE, McCracken LM. A systematic review of randomized controlled trials of Acceptance 
and Commitment Therapy for adults with chronic pain: Outcome domains, design quality, and efficacy. 
J Contextual Behav Sci. 2014;3(4):217–27. 
21. 
McCracken LM, Morley S. The psychological flexibility model: A basis for integration and 
progress in psychological approaches to chronic pain management. J Pain. 2014;15(3):221-34. 
22. 
Powers MB, Zum Vörde Sive Vörding MB, Emmelkamp PM. Acceptance and commitment 
therapy: A meta-analytic review. Psychother Psychosom. 2009;78(2):73-80. 
23. 
Öst L-G. The efficacy of Acceptance and Commitment Therapy: An updated systematic review 
and meta-analysis. Behav Res Ther. 2014. 
24. 
Hayes SC, Pistorello J, Levin ME. Acceptance and commitment therapy as a unified model of 
behavior change. Couns Psychol. 2012;40(7):976-1002. 
25. 
Huggins JL, Bonn-Miller MO, Oser ML, Sorrell JT, Trafton JA. Pain anxiety, acceptance, and 
outcomes among individuals with HIV and chronic pain: A preliminary investigation. Behav Res Ther. 
2012;50(1):72-8. 
26. 
Wetering EJ, Lemmens KM, Nieboer AP, Huijsman R. Cognitive and behavioral interventions 
for the management of chronic neuropathic pain in adults–a systematic review. Eur J Pain. 
2010;14(7):670-81. 
27. 
Evans S, Fishman B, Spielman L, Haley A. Randomized trial of cognitive behavior therapy 
versus supportive psychotherapy for HIV-related peripheral neuropathic pain. Psychosomatics. 
2003;44(1):44-50. 
28. 
Cucciare MA, Sorrell JT, Trafton JA. Predicting response to cognitive-behavioral therapy in a 
sample of HIV-positive patients with chronic pain. J Behav Med. 2009;32(4):340-8. 
29. 
Trafton JA, Sorrell JT, Holodniy M, Pierson H, Link P, Combs A, et al. Outcomes associated 
with a cognitive-behavioral chronic pain management program implemented in three public HIV 
primary care clinics. The journal of behavioral health services & research. 2012;39(2):158-73. 
30. 
Miaskowski C, Penko JM, Guzman D, Mattson JE, Bangsberg DR, Kushel MB. Occurrence 
and characteristics of chronic pain in a community-based cohort of indigent adults living with HIV 
infection. J Pain. 2011;12(9):1004-16. 
31. 
Breitbart W, Rosenfeld BD, Passik SD, McDonald MV, Thaler H, Portenoy RK. The 
undertreatment of pain in ambulatory AIDS patients. Pain. 1996;65(2):243-9. 
32. 
Green CR, Anderson KO, Baker TA, Campbell LC, Decker S, Fillingim RB, et al. The unequal 
burden of pain: confronting racial and ethnic disparities in pain. Pain Med. 2003;4(3):277-94. 
33. 
Sullivan LW, Eagel BA. Leveling the playing field: recognizing and rectifying disparities in 
management of pain. Pain Med. 2005;6(1):5-10. 
34. 
Golin C, Isasi F, Bontempi JB, Eng E. Secret pills: HIV-positive patients' experiences taking 
antiretroviral therapy in North Carolina. AIDS Educ Prev. 2002;14(4):318-29. 
35. 
Ware NC, Wyatt MA, Tugenberg T. Social relationships, stigma and adherence to antiretroviral 
therapy for HIV/AIDS. AIDS Care. 2006;18(8):904-10. 
36. 
Miles MS, Isler MR, Banks BB, Sengupta S, Corbie-Smith G. Silent endurance and profound 
loneliness: Socioemotional suffering in African Americans living with HIV in the rural south. Qual 
Health Res. 2011;21(4):489-501. 

 
 
 
 
 
   
 
 
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37. 
Teti M, Bowleg L, Lloyd L. ‘Pain on Top of Pain, Hurtness on Top of Hurtness’: Social 
Discrimination, Psychological Well-Being, and Sexual Risk Among Women Living With HIV/AIDS. 
International Journal of Sexual Health. 2010;22(4):205-18. 
38. 
Zukoski AP, Thorburn S. Experiences of stigma and discrimination among adults living with 
HIV in a low HIV-prevalence context: a qualitative analysis. AIDS Patient Care STDS. 2009;23(4):267-
76. 
39. 
Zelman DC, Gore M, Dukes E, Tai K-S, Brandenburg N. Validation of a modified version of the 
brief pain inventory for painful diabetic peripheral neuropathy. J Pain Symptom Manage. 
2005;29(4):401-10. 
40. 
Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, et al. Comparison of pain 
syndromes associated with nervous or somatic lesions and development of a new neuropathic pain 
diagnostic questionnaire (DN4). Pain. 2005;114(1-2):29-36. 
41. 
Bouhassira D, Lanteri-Minet M, Attal N, Laurent B, Touboul C. Prevalence of chronic pain with 
neuropathic characteristics in the general population. Pain. 2008;136(3):380-7. 
42. 
Kroenke K, Spitzer RL, Williams JB. The PHQ‐9. J Gen Intern Med. 2001;16(9):606-13. 
43. 
Woldeamanuel Y, Kamerman P, Veliotes D, Phillips T, Asboe D, Boffito M, et al. Development, 
Validation, and Field-testing of an Instrument for Clinical Assessment of 
HIV-associated Neuropathy and Neuropathic Pain in Resource-restricted and Large 
Population Study Settings. PLoS One. Submitted. 
44. 
Merlin JS, Walcott M, Ritchie C, Herbey I, Kertesz SG, Chamot E, et al. ‘Two pains together’: 
Patient perspectives on psychological aspects of chronic pain while living with HIV. PloS one. 
2014;9(11):e111765. 
45. 
Taylor B, Carswell K, de C Williams AC. The interaction of persistent pain and post-traumatic 
re-experiencing: a qualitative study in torture survivors. J Pain Symptom Manage. 2013;46(4):546-55. 
46. 
Stinson JN, Toomey PC, Stevens BJ, Kagan S, Duffy CM, Huber A, et al. Asking the experts: 
Exploring the self‐management needs of adolescents with arthritis. Arthritis Care Res. 2008;59(1):65-
72. 
47. 
Braun V, Clarke V. Using thematic analysis in psychology. Qualitative research in psychology. 
2006;3(2):77-101. 
48. 
Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, et al. Comparison of pain 
syndromes associated with nervous or somatic lesions and development of a new neuropathic pain 
diagnostic questionnaire (DN4). Pain. 2005;114(1):29-36. 
49. 
Bouhassira D, Lantéri-Minet M, Attal N, Laurent B, Touboul C. Prevalence of chronic pain with 
neuropathic characteristics in the general population. Pain. 2008;136(3):380-7. 
50. 
Zelman DC, Dukes E, Brandenburg N, Bostrom A, Gore M. Identification of cut-points for mild, 
moderate and severe pain due to diabetic peripheral neuropathy. Pain. 2005;115(1):29-36. 
51. 
Von Korff M, Ormel J, Keefe FJ, Dworkin SF. Grading the severity of chronic pain. Pain. 
1992;50(2):133-49. 
52. 
Cherry CL, Wesselingh SL, Lal L, McArthur JC. Evaluation of a clinical screening tool for HIV-
associated sensory neuropathies. Neurology. 2005;65(11):1778-81. 
53. 
Francis JJ, Johnston M, Robertson C, Glidewell L, Entwistle V, Eccles MP, et al. What is an 
adequate sample size? Operationalising data saturation for theory-based interview studies. 
Psychology and Health. 2010;25(10):1229-45. 
54. 
Guest G, Bunce A, Johnson L. How many interviews are enough? An experiment with data 
saturation and variability. Field methods. 2006;18(1):59-82. 

 
 
 
 
 
   
 
 
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55. 
Penrod J, Preston DB, Cain RE, Starks MT. A discussion of chain referral as a method of 
sampling hard-to-reach populations. J Transcult Nurs. 2003;14(2):100-7.