Participants, interventions and outcomes

Primary care settings in two localities: London and the Midlands.

The population of interest are adults living with chronic migraine or chronic tension type headache, with or without medication overuse. Part of the challenge in interpreting the findings of research in people living with chronic headaches is the often poor reporting of participants’ phenotypic characteristics, meaning it is not possible to draw conclusions for specific chronic headache types.^{13 20} For this trial, it is important that we are able to define our participants’ headache type, or types, accurately and exclude those with non-eligible headache types. We, therefore, developed and validated a logic model for use in a telephone interview by a nurse (non-headache expert) that would allow us to identify and classify people meeting our entry criteria while also excluding people with secondary headaches, other than medication overuse and other causes of primary headaches (table 1).²¹

Inclusion and exclusion criteria

Able and willing to comply with the study procedures and provide written informed consent.

Aged ≥18 years (no upper limit).

Living with chronic headache; defined as headache on 15 or more days per month for at least the preceding 3 months.

The nurse telephone classification interview confirms headache type to be chronic migraine, or chronic tension type headache, with or without medication overuse headache.

Fluent in written and spoken English.

Unable to attend the group sessions.

No access to a telephone (for classification interview).

Has an underlying serious psychological disorder with ongoing symptoms that preclude or significantly interfere with participation in the group intervention.

Previous entry or randomisation in the present trial.

Currently participating in another clinical trial of headache treatments or unregistered medicinal product or less than 90 days have passed since completing participation in such a trial.

Pregnancy is not an exclusion criterion. However, any pregnant women randomised to the active intervention will be advised to speak to their GP with regards to medication, and the CHESS intervention nurses will not discuss this with them during the consultation for safety reasons.

Our previous experience is that the challenges of running non-English language group interventions for chronic painful disorders are too great to do successfully within an RCT.²² Furthermore, the main outcomes are not validated in those languages other than English, which are relevant to a UK context. For these reasons, we are excluding people who are not fluent in written and spoken English.

In this pragmatic trial, our entry criteria reflect the point in the care pathway where our intervention will be offered. Specifically, general practitioners will refer people they identify with chronic headaches into the service. Thus, there is not the pre randomisation run-in one might expect in a more explanatory drug trial, and we base assessment of the presence of chronic headache on a single telephone assessment and include a mixture of headache types.

The intervention consists of a group education and self-management programme, an 8-week headache paper diary, a one-to-one nurse-led consultation and follow-up telephone calls, where necessary, for up to 8 weeks. We have described its development in detail elsewhere.²³ We summarise it briefly here.

The programme is run over 2 days in a 2-week period for around 10 participants per group (target 6–12 participants) and is facilitated by two intervention trained healthcare professionals, at least one of whom is a nurse (the second facilitator could be a nurse or other registered allied health professional such as psychologist, physiotherapist, chiropractor and occupational therapist). We originally planned to run sessions using a nurse and a lay facilitator living with chronic headaches. However, in our feasibility study, we found it difficult to recruit people living with chronic headaches to act as facilitators and of those that were recruited several found it difficult to commit to facilitation of courses because of the unpredictability of their condition. The intervention builds on a previously developed and tested educational and cognitive behavioural self-management intervention for people with chronic musculoskeletal pain.²⁴

The aim of the course is to encourage and enable those with chronic headaches to recognise unhelpful thought patterns and behaviours that contribute to their headache burden and to do something about them. The course provides participants with an overall toolbox of strategies that could help in the management of their headaches. These strategies include psychological techniques to change perceptions and feelings about living with chronic headaches as well as more practical strategies around lifestyle factors and medication. The group intervention is delivered using a range of methods including: group discussions, ideas generation, sharing narratives and experiences, problem solving, role play and taster activity sessions. The programme includes a range of behaviour change techniques including: barrier identification, general encouragement, instruction from the group facilitators, provision of feedback and allowing opportunities for social comparison in the group. We also include an educational video (available on disc and online) following feedback from our PPI group on the importance of having something to show family and friends about their ‘invisible’ disorder.

The sessions take place on weekdays and, where possible, during school hours to accommodate those with child care responsibilities. Sessions are held in easily accessible community venues and GP practices.

Participants in the intervention arm are asked to complete a paper headache diary for a period of up to 8 weeks prior to the 2-day programme. A one-to-one, individually tailored nurse-led consultation follows the 2-day programme. During this session, the nurse classifies the participant’s headache type, discuss medication and lifestyle factors and explore participants’ goals. This discussion is backed up by written information (for patient and GP), consistent with NICE guidance, to support shared informed decision making between the patient and their GP, about medication choices.²⁵ All participants will be offered telephone follow-up for up to 8 weeks. The frequency of these follow-up calls will be individually negotiated and agreed with participants during the one-to-one consultation. Full details of the intervention content have been published elsewhere.²³

Previous studies of this nature have reported that a usual care control arm was not an incentive to join the study.¹⁵ We know from experience that patients enjoy the relaxation part of pain self-management programmes.¹⁷ Therefore, as an incentive to participate, the control group receive standard usual care plus a relaxation CD and instructions for use over the duration of the study, up until final follow-up at 12 months. Participants are free to continue using the relaxation CD thereafter should they wish.

As all participants in the trial have a headache classification interview prior to randomisation, we feed back the results of that classification interview to control participants, and their GPs, together with advice on headache management. In this way, we ensure all participants receive best usual care.

The relaxation CD or downloadable MPG file (from the CHESS website) consists of a 17 min relaxation audio script that starts by focusing on the breath before talking the participant through progressive relaxation of muscles. The participants in the control group choose when, where and how often they do the relaxation but are advised to try it two to three times a week or as often as they feel appropriate over the course of the study.

All group sessions have two facilitators: one of whom must be a registered nurse, while the other facilitator is any allied healthcare professional, registered with a regulatory body, with an interest in this patient population and condition. Facilitators were recruited via advertisements in allied healthcare profession organisations and trained over a 2-day period to deliver the self-management intervention. Nurses received a further day of training to cover the one-to-one consultations. The training course covers the content of the intervention, facilitation skills, managing groups and trial procedures. Those undergoing the training were assessed using a learning assessment form at the end of the training course to check their knowledge and understanding. Those evaluated to be competent were asked to deliver the intervention. Those who either struggled with some elements of the content or expressed any concerns about delivering the intervention were provided with additional one to one support by the trainers.

Quality assurance of the intervention is important to ensure that the trial intervention is delivered consistently and in accordance with the trial protocol and manuals. As part of the intervention development, we have produced two very detailed manuals: the first that covers the 2 days of group sessions and the second that details the process for the one to one consultations. All facilitators have been appropriately trained on the delivery of the intervention in accordance with the manuals. They have been instructed to use the manuals to guide them through delivery of the intervention.

To assure the quality of the course delivery, we will aim to observe each facilitator. We will observe each facilitator early in their facilitation to allow any difficulties or challenges to be addressed. Subsequently, they will be observed midway through. Observations will be by session, and the number of sessions observed will depend on the ability of the observer to capture the required information.

The observations will be conducted by members of the CHESS team who have knowledge of the intervention and its delivery. Observers will complete an observation form that will address facilitator skills and adherence to content delivery. Feedback will be provided on the day where possible. If this is not possible, the observer will arrange to contact the facilitator by phone. The study team will discuss any difficulties with the facilitator to minimise impact on the rest of the course and to help with the delivery of future courses. For any facilitators struggling, the central research team will monitor their personal reflections for the remaining duration of the course and follow-up with phone calls if required.

Our primary outcomes is headache-related quality of life assessed at the primary endpoint, 12 months after randomisation. For sample size determination, we have specified the Headache Impact Test (HIT-6), a six-item patient-reported outcome measure (PROM), as our measure of the primary outcome.²⁶ The HIT-6 provides a short overall assessment of headache impact – with items assessing fatigue, pain, social functioning, emotional well-being and cognition. Prior to selecting our outcome measures, we did a systematic review of PROMs for headaches.²⁷ Only for the HIT-6 did we find acceptable evidence supporting its use for our target population who may not have been given a headache diagnosis prior to study entry.

Another measure, shortlisted in the review, was the 14-item Migraine-Specific Quality of Life Questionnaire (MSQ v2.1) assesses the role restrictions, limitations and emotional impact of migraine.²⁷ The MSQv2.1 has acceptable evidence of psychometric properties following completion in a migraine population.^27–30

To inform our selection of outcome measures, we undertook interviews (n=14) with people with chronic headache. Our participants described greater perceived relevance of the MSQ (v2.1) compared with the HIT-6. With permission from GSK, the copyright holders, we modified the MSQ (v2.1), changing the focus from ‘migraine’ to ‘headache’; the modified measure was renamed as the ‘Chronic Headache Quality of Life Questionnaire’ (CHQLQ v1.0). In our ongoing work, we are assessing the performance of this modified instrument. In the event its performance is superior to the HIT-6, we will consider changing the primary outcome.

Both the HIT-6 and the CHQLQ v1.0 will be collected via postal questionnaire at baseline, 4, 8 and 12 months post randomisation.

The following secondary outcome measures are being collected:

Headache days: our main outcome describing headaches days will be headaches days in the preceding month reported at baseline and follow-up postal questionnaires. We will also estimate total headaches days over the whole study period from patient-reported data collected via a smartphone app.

Headache impact: we will assess headache impact based on their typical duration and severity reported in baseline and follow-up questionnaires.

Composite headache outcome: we will produce a composite headache outcome of headache days × severity × duration using data from the smartphone app and questionnaires.

Generic health-related quality of life: we have included two standard measures of health-related quality of life—the (SF-12 V2) Short Form Survery 12 Version 2 and (EQ-5D-5L) EuroQol five dimension scale.^31–33 There is limited, but acceptable, evidence supporting the use of the SF-12 V2 to assess overall quality of life in a headache population.²⁷ There is no such evidence for the EQ-5D-5L.²⁷ We will, therefore, use EQ-5D-5L primarily for our health economic analyses.³²

Emotional well-being: Hospital Anxiety and Depression Scale (HADs) – psychological distress is extremely common in people living with chronic pain. HADs has been used in many previous studies of chronic pain, including the COPERS (Coping with persistent Pain, Effectiveness Research into Self-management) study where we identified positive effects on both anxiety and depression in a chronic pain population.^{22 34}

Self-efficacy: Pain Self-Efficacy Questionnaire (PSEQ) – self-efficacy is an important mediator for how self-management interventions may improve patient outcomes. It is important, therefore, to measure change in self-efficacy as part of understanding the causal pathway for any change and informing our process evaluation.³⁵ We have previously reviewed measures of self-efficacy and concluded that PSEQ is the most appropriate choice for studies of this nature; although all current measures have limitations.³⁶

Social activity: Social Integration Subscale (SIS) of the Health Education Impact Questionnaire (heiQ) – chronic headache can result in a disrupted lifestyle and a reduced quality of life both during and between attacks; the impact of chronic headache on an individual’s ability to commit to social plans is an important aspect of quality of life. Successful treatment should seek to improve both overall quality of life, as well as an individual’s quality of life during the attack, including their ability to integrate in society. A well-developed, condition-specific measure should seek to capture these distinctions. The five-item SIS is one of eight domains contained within the heiQ, a measure of the impact of patient education programmes in chronic conditions.³⁷

Bodily pain: chronic headache commonly coexists with other chronic painful disorders such as low back pain.^38–41 The CHESS intervention might affect the troublesomeness of other bodily pains. We will collect these data using a previously validated Troublesomeness Grid.⁴²

At baseline we also collect data on age, gender, ethnic group, age at leaving full-time education and current work status.

We will collect follow-up data at 4, 8 and 12 months after randomisation by postal questionnaire survey. A £5 high street voucher is enclosed as a token of our appreciation at each initial time point. We will send out two postal follow-up reminders. In the event that no response is obtained, we will aim to collect our primary clinical outcome data by telephone. This includes the HIT-6 and EQ-5D-5L.

The smartphone data will be collected weekly for 6 months from initial eligibility and then monthly until 12 months after randomisation. A paper version of the app will be available to those who do not use a smartphone.

If there are missing data (for our key clinical outcomes), this will be followed up with the participant who completed the form, as soon as possible by a member of the team over the phone. We will phone the participant and enter the correct information onto the form; this will be initialled and dated.

Figure 1 shows the recruitment flow, and table 2 shows the study timelines.

This shows the recruitment flow chart.*Genetal practitioner; National Migraine Center; Definite Chronic Migraine; Probable Chronic Migraine; Tension Type He adache; Medication Overuse He adache. DMC, definite chronic migraine; GP, general practitioner; MOH, medication overuse headache; PCM, probable chronic migraine; TTH, tension type headache.

Schedule of enrolment, interventions and assessments

CHQLQ, Chronic Headache Quality of Life Questionnaire; EQ-5D-5L, EuroQoL; HADs, Hospital Anxiety and Depression Scale; HeiQ, Health Education Impact Questionnaire; HIT-6, Headache Impact Test; PO, Primary outcome; PSEQ, Pain Self-Efficacy Questionnaire; SF12, Short Form 12-item Health Survey.

For the purposes of our sample size calculation, the primary clinical outcome is the difference in mean HIT-6 score at 12 months post randomisation between the self-management group programme and the usual care relaxation therapy (control arm). The HIT-6 outcome measure is a continuous scale with higher values indicating more severe impact on daily life. From our systematic reviews, we anticipate a worthwhile difference to be 2.0, that is, mean outcome in the control arm is 2.0 units higher than for the intervention.^{27 43} In our feasibility study (n=114), the SD of the HIT-6 score at baseline was 6.87.⁴⁴

Participants are randomised to either the self-management group or usual care and relaxation therapy. In this design, there may be a clustering effect in the self-management group and not in the control arm, which needs to be allowed for in the sample size calculation. Based on similar trials, we assume that the intraclass correlation coefficient is 0.01.²² The anticipated average size of the self-management programme is 10.

The minimum sample size required was estimated using Moerbeek and Wong’s method to account for grouping in one arm.⁴⁵ To detect a between-group difference of 2.0 with SD of 6.9 (a standardised mean difference of 0.29) and assuming that the ratio of the total variance in the self-management group to the relaxation therapy is 1 at the two-sided 5% significance level and at least 90% power, the sample size required is 523 participants (253 in the relaxation group and 270 in the self-management group).

In the feasibility study, the overwhelming majority of those recruited, approximately 95%, chronic migraine; just 5% had chronic tension type headache. We want to be able to draw definite conclusions on the specific subgroup of chronic migraine. Therefore, we will base our sample size and primary clinical outcome on the population with chronic migraine. Therefore, based on 95% of our sampled population with chronic migraine and accounting for a 20% loss to follow-up as above, the sample size we would require is 689 with 333 to the relaxation arm and 356 to the self-management programme.

In the feasibility study, we recruited around 1/1000 of practice population to take part⁴⁴; we therefore anticipate we need to recruit from around 100 general practices with a combined list size of around 700 000.

In consultation with the Data Monitoring and Ethics Committee (DMEC), we will review the sample size around halfway through recruitment to ensure we have recruited sufficient participants with chronic migraine and revise our estimates using within trial data on the variance of our primary outcome at baseline. This review will be based on the headache classification and actual baseline SD of our sampled population. We might also need to recruit some additional participants to ensure that the final group sessions at each site are adequately populated.

Participants are identified and invited into the study in two ways. First, practices run electronic searches on their databases to identify people who have consulted with headaches or have been prescribed migraine specific drugs (eg, triptans and pizotifen) in the preceding 2 years. Practices then screen the lists for those it would be inappropriate to approach (eg, poorly controlled serious mental illness, terminal illness or known secondary causes of headache such as primary or secondary brain tumours) and send approach letters to the remainder.

People can self-refer to the trial. Participating general practices, the principal pharmacies used by their patients, are supplied with a study poster for display in patient areas inviting people to contact the study team if they have headaches and are interested in participating. Information about the trial is made available on the poster (in general practices and pharmacies) and websites (https://warwick.ac.uk/fac/med/research/ctu/trials/other/chess/ and https://warwick.ac.uk/fac/med/research/ctu/trials/chess. People who find about the trial through the internet or following media exposure, and can travel to sessions, can also self-refer to the trial.

Using both approaches will allow people receiving GP treatment for chronic headaches who are not coded in the GP system as having headaches, and those who are self-medicating their headaches, the opportunity to join the study. We anticipate that we will primarily recruit people registered with participating practices; however, we will not restrict recruitment to those registered with participating practices.

In addition to these two main recruitment strategies, a study press release was submitted in January 2018, which was picked up by various media outlets and generated further interest in the study from potential participants.

The study coordinating team contact people expressing an interest in the study and check that they are eligible, explain the study and obtain participant’s verbal consent to start completing an electronic headache symptom severity, duration and frequency diary (or paper version where there is no access to the internet). The electronic diary is completed weekly for the first 6 months and subsequently monthly until the end of follow-up at 12 months. The electronic diary is used to identify any early effects of rebound headache in those with MOH. At this time participants are sent a baseline questionnaire and consent form to return in a freepost envelope.

Following receipt of baseline questionnaire and consent form, participants are contacted by phone for a nurse headache classification interview. People whose headache is confirmed to meet our entry criteria are then eligible for randomisation. If the nurse has a concern that the potential participant may have another headache type, there is a second interview with a doctor skilled in the management of headache disorders from the National Migraine Centre (http://www.nationalmigrainecentre.org.uk/). This is to ensure no one is inappropriately excluded and that people with a headache type needing more specific treatment are directed towards appropriate treatment. For example, 2/108 people in our feasibility study had cluster headaches.⁴⁴ In such cases, we write to the GP and the participant with details on the excluded headache type and explain that they no longer fit the inclusion criteria for the CHESS trial.