Planeación del proyecto y reconocimiento del componente estadístico

The study design chosen for the WEST headache trial was a two group parallel RCT. A within group design such as a cohort study following patients with CTTH and taking measurements before and after treatment was an option to evaluate sauna bathing in patients with CTTH. Three studies of sauna bathing for chronic pain (Matsumoto, et al., 2011; Matsushita, et al., 2008; Oosterveld, et al., 2009) employed a cohort study design. Each participant serves as his or her own control with the time period before treatment compared to the time period after the treatment for measures such as headache intensity, duration and other parameters (Grady, Cummings, & Hulley, 2001).

A pilot study was not performed prior to the clinical trial in this PhD project however pre study testing was performed. The PI had experience of the effects of repeated sauna bathing on several patients with chronic pain over at least 12 months prior to this PhD study and found that eight weeks of regular attendance was sufficient to reduce pain intensity.

Therefore the dose of the intervention was ascertained. The diary was developed and tested on clinic patients prior to the RCT to test these for readability and any difficulties

participants may face when filling in the headache diary. The validated questionnaires were also filled in by patients in the clinic to ensure these were easy to understand and fill in. Staff at the Southern Cross Specialist Centre was also trained to administer the

questionnaire prior to the RCT starting.

The options to perform an observational study such as a cohort study were considered. The cohort study would have been simpler to perform and could have served as a pilot study on which to base a future RCT with information gained to compute sample size, recruitment trends and a chance to trial questionnaires and procedures. The cohort study would not have given the PI experience on aspects of RCTs such as randomisation and statistical analysis comparing two groups. The major disadvantages of within group designs is the lack of concurrent controls and improvements may be due to regression to the mean (participants

their baseline symptoms) or perhaps seasonal trends (if winter was the worst period for TTH then if the study started in winter there would be an improvement as the weather improved) (Grady, et al., 2001).

The randomisation procedure of this RCT was based on computer generated random numbers. Randomisation of matched pairs may have been an option to ensure matching of characteristics such as age, sex and headache severity between the two groups. This design may reduce confounding variables on the outcome measures, however to match pairs the clinical trial could not get underway until enough participants enrolled to begin the

matching process. Due to time constraints a classic randomisation was adopted rather than matched pairs.

Researchers are often interested in measurements of outcome before and after the intervention to substantiate or negate the effect of an intervention, which means pre and post testing is required. Two commonly used study designs are cross over and parallel control (Hopewell, et al., 2010). A parallel group trial is when two or more groups are followed simultaneously. In a cross over design participants have the study intervention followed by the control treatment, or the control intervention followed by the study

intervention. There is a washout period in between the two interventions to account for any residual effects of the first intervention. This approach increases statistical power and reduces the numbers of participants required, however disadvantages include carryover effect and increased length of time for the trial to be performed. The carryover effect is the residual effect of the intervention on the outcome after it has been stopped and a washout period can be introduced to eliminate the carryover effect. A cross over design has been used in six RCTs for CTTH (section 3.7) (Bendtsen & Jensen, 2000, 2004; Fogelholm & Murros, 1992; Langemark & Olesen, 1994; Lindelof & Bendtsen, 2009; Shukla, et al., 1996). The carryover effect and washout period of sauna bathing are unknown and a parallel group design was selected over a cross over design for this PhD study.

whether they were allocated to the intervention or control group, which is consistent with trials of non pharmaceutical intervention trials of CTTH (section 3.7). The information sheet for the trial (Appendix 5) states there are two treatment groups of which one will attend the sauna, however no mention is made whether this is the intervention group or control group and several participants commented that they thought the sauna group was the control or inactive treatment group. None of the nonpharmaceutical trials reviewed in section 3.7 (Holroyd, et al., 2001; Kiran, et al., 2005; Soderberg, et al., 2006; Wang, et al., 2007) were double blind with both treatment provider and participant blind to treatment allocation.

While an RCT on sauna bathing for CTTH may address whether this intervention may be a worthwhile intervention to relieve pain and other headache parameters, the design chosen is unable to prove the Adrenaline Model of Headache Causation or provide a direct link between SNS tone and the presence or severity of CTTH. Thus far research has shown that repeated sauna bathing reduces SNS activity in patients with an elevated SNS tone (e.g. congestive heart failure) (Kihara, et al., 2004; Miyamoto, et al., 2005). Research in the form of one RCT (Masuda, Koga, et al., 2005) and two cohort studies (Matsumoto, et al., 2011; Matsushita, et al., 2008) has also shown that regular sauna bathing has the potential to be a useful intervention for chronic pain. The PI’s principal aim in carrying out an RCT was to test whether regular sauna bathing, a self directed non invasive therapy, may offer pain relief for patients suffering from chronic pain. Unfortunately if headache intensity reduces from regular sauna bathing, the mechanism by which sauna bathing is acting will be unproven. There are no measures of SNS activity in the trial design. Discussions were held with supervisors on measuring serum noradrenaline and other parameters of SNS activity. The drawbacks of taking serum samples of SNS markers were increased costs (no budget was available for personnel to take bloods or for the required assays) and subjecting participants to blood tests (that may have made participation in this RCT less attractive). If this RCT showed positive results, then funding agencies may be more likely to provide funding in future studies to allow measurements such as noradrenaline levels and HRV before and after the intervention period. It would be interesting to see whether pain reduced

be addressed in the future.

The WEST headache trial was to include a baseline observation period of four weeks followed by an intervention period of eight weeks. The timeline is shown in Figure 6.1. Several trials looking at the prevention of CTTH had a four week baseline diary and eight weeks of treatment (Bendtsen, et al., 2007; Bettucci, et al., 2006; Padberg, et al., 2004; Ribeiro, 2000; Schmitt, et al., 2001). This timeframe was deemed as adequate to identify a treatment effect of sauna bathing as identified from anecdotal evidence with test subjects with CTTH who underwent sauna bathing prior to the WEST headache trial (Chapter 2).

Once participants contacted the Southern Cross Hospital or the PI, they were screened by the PI in a telephone interview to ensure they met the inclusion criteria and no exclusion criteria were present. A detailed analysis of the type of headache the potential participants experienced was discussed, to ensure other headache disorders such as migraine or cluster headache were excluded. Participants were then advised about the study and if they were interested in participating were sent an information sheet (Appendix 5) and a four week headache diary (Appendix 6) to record headache intensity (NPRS) and headache duration (hours/day). Participants were asked to make their initial appointment once they completed their four week headache diary. Once they completed their baseline diary they attended the initial consultation with the PI.

Prior to the initial consultation a questionnaire (Appendix 7) was filled in to obtain baseline data including demographic information, medication usage, sleep disturbance score

(Vernon, Brandenburg, Alvir, Griesing, & Revicki, 2008), BDI (Beck, Steer, & Carbin, 1988 ) and HDI (Jacobsen, Ramadan, Aggarwal, & Newman, 1994). The questionnaire was administered by a nurse at the Southern Cross Specialist Centre. Participants were also given a consent form to read.

The initial consultation was approximately 45 minutes duration. Participants were given an explanation of the trial and questions about the trial were answered. A consent form was

was checked to ensure they met the CTTH criteria of 15 headaches per month. A clinical history and examination were performed to exclude any obvious secondary cause of headache and confirm the headache conformed to the International Headache Society definition of CTTH. The Adrenaline Model of Headache Causation was explained to all participants with a handout given to them for future reference (Appendix 9) and how to perform soft tissue massage also with a handout (Appendix 10). The intervention group was given cards that allowed complementary attendance at the Wellington City Council swimming pool saunas and advised to attend three times a week for 20 minutes.

Participants were given an eight week daily headache diary to record headache intensity and duration. All participants were phoned two weeks into their treatment to ensure there were no difficulties with their treatment or adverse effects. After the eight week headache diary participants attended the final consultation. Prior to the final consultation the study questionnaire including BDI, HDI and sleep disturbance scores were administered by the nurse. At the final consultation participants were questioned about difficulties in

completing the treatment assigned and compliance.

Both groups received the same education outlining the Adrenaline Model of Headache Causation with handout (Appendix 9) and training for soft tissue massage with a handout (Appendix 10). The number of appointments, time spent at appointments, data collected and consultation were the same for all participants in the study. The only difference was the instruction to attend the sauna for the intervention group (Appendix 11).