We undertook RheumAFooT as an exploratory phase II trial of podiatry care for patients with RA. Important information was gathered to inform the design and implementation of a definitive RCT. By controlling for potentially significant confounders on the main outcome, particularly pharmacological management and co-morbidity, we encountered recruitment problems. The pragmatic design revealed important problems for, (1) defining the start of treatment, (2) variation in delivery of treatment and (3) use of other medical and allied health services. However, involving a patient focus group beneficially facilitated the design and implementation of the trial especially with regards to incorporating a non-intervention arm. Acknowledging the limitations of an exploratory trial, the findings suggest that podiatry-led foot care as a complex intervention maintains but does not improve foot related impairment or disability in patients with stable controlled disease. However, no treatment leads to a small deterioration in foot health related to impairment but not disability.
There were two main challenges to recruitment in this study-stable drug management and co-morbid disease. As with all rehabilitation strategies in RA, non-pharmacological interventions are adjunct to drug management. With such powerful effects on symptoms and disease activity such combinations pose a challenge for outcome evaluation, especially for a disease with natural variation in its presentation over months and years. On reflection, the criteria set here for no change in either drug type or dosage was too stringent. Moreover, choice of medication or dosage may be changed for reasons other than controlling the disease process-tolerance and side-effects for example. Additionally, the study was based in an outpatient clinic attached to an academic unit and as such close monitoring of patients may have led to more frequent intervention. For a definitive trial it would be important to gauge the level of drug monitoring and intervention in other secondary and primary care settings to help set more pragmatic exclusion rules. Alternatively the interaction with between pharmacological and non-pharmacological treatments and changes in disease severity could be handled by statistical analyses or minimised between groups although these are difficult to anticipate. How this problem is handled in other non-pharmacological trials in RA is not well documented.
Co-morbid disease excluded one fifth of patients approached for this study, the main reasons being diabetes mellitus and peripheral vascular disease. However, exclusion was not based on diagnosis alone and was limited to those who were at risk from developing foot-related complications, primarily infection and foot ulceration. In reality most of these patients were excluded as they were in receipt of foot care or assessment/advice in other specialist clinics such as the hospital diabetic foot clinic. Exclusion by co-morbid disease requires more precise definition in future trials and should look beyond diagnosis and towards related complications and secondary treatment.
We found that over one-third of patients refused to participate in the trial. Our main concern was the use of a non-intervention arm. However, additional visits to clinic (as raised in the patient focus group), lack of perceived understanding of role and the benefit/risks of podiatry care were the three most common reasons for refusal. Indeed only one patient declined following allocation to the non-intervention group to seek care and this was matched by one patient in the intervention arm who did not want additional hospital visits. Organisations such as the Arthritis Research Campaign provide leaflets specifically detailing foot problems and their treatment but availability in outpatient clinics and uptake is not known. These findings indicate that in a definitive trial, like any new or novel treatment, the potential benefits and hazards of podiatry-led foot care must be fully explained during the recruitment of patients before they make an informed choice. Throughout the trial we were encouraged that loss to follow up was comparable between groups with no strong evidence of resentful demoralisation (deliberate withdrawal of patients in the control group who perceive differential benefit for the intervention group).
The findings suggest that a non-treatment parallel arm can also be used in a definitive trial. However, other approaches such as a patient preference design or unequal randomisation, e.g., 2:1 in favour of receiving the intervention, could improve recruitment . Alternatives, such as a minimal or sham intervention arm, for example using an information leaflet or sham insole, could also be considered. However, sham procedures are not suitable within pragmatic trials as they do not model usual practice. Furthermore, sham physical agents mimicking interventions such as scalpel debridement and foot orthotics may have physiological effects that are therapeutic . Indeed, we have encountered this problem in a previous trial and do not favour this approach .
In this exploratory trial the groups were well balanced at baseline for all but one demographic or disease variable indicating that the automated randomisation worked and was feasible for this type of study. In a definitive trial, we suggest the use of minimisation – where patients are allocated to a particular treatment depending on the characteristics of those participants already enrolled. Minimisation ensures excellent balance across important prognostic factors and is recommended for small trials . Factors to minimise imbalance should include age, gender, disease duration, and disease severity.
Significant variation in the type and frequency of podiatry interventions was not an unexpected finding for an exploratory trial with a pragmatic design. However, this approach revealed important factors about the delivery of podiatry care. For example, the definition of the start of treatment was imprecise since patients frequently received an initial assessment consultation and then further appointments during the work up to a physical intervention such as customised orthoses. Notwithstanding the potential non-specific benefits from these consultations, the main physical treatment was often started some months later from baseline assessment. In the present study we also underestimated the 'gatekeeper' role of podiatrist as the rates of referral to other experts was much higher than expected. The extent to which these findings represents local practice or are generalisable to secondary care provision in the UK is unclear. However, with a lack of care pathways and published clinical guidelines further modelling, as suggested in the preclinical and phase I stages of the MRC framework, is required in other centres to define more precisely the constituent parts of podiatry care as well as the extent of other medical, allied health, surgical and self-care involvement. This potential lack of standardisation represents a significant challenge should a definitive trial remain pragmatic and expanded to multi-centre design.
The LFIS provides us with a well-validated patient-focused outcome for use in this type of trial . In an exploratory analysis we detected no change in foot-related impairment and disability and slight deterioration in impairment in the intervention and no interventions groups respectively. This was observed against a backdrop of stable, well-controlled disease. The study was not adequately powered for this outcome but the data generated here and in other pilot studies in our unit will beneficially inform a robust sample size calculation for a definitive trial. For example, based on (previously unreported) data from 141 cases for the primary outcome of LFISIF, a minimally clinically important difference would be 3 points with a standard deviation of 5 points. For a two treatment parallel-design RCT of podiatry-led foot care versus no foot care, 85 per group would be required to detect a difference between the groups of 3 point, based on 90% power and 1% significance level. According to figures from this pilot, a 20% loss to follow-up would be expected so a total sample size of 102 per arm would be required.
Embedded within in a definitive trial should be a qualitative study appraising patient's perceptions and beliefs about their foot care experiences. Efficacy and side-effects are important factors in the evolving experience of RA patients treated pharmacologically, for example with DMARD therapy . Our focus group work revealed low expectation and lack of outcome may have been influenced by poor understanding of the role of podiatry; prior experience from home or over-the-counter remedies such as insoles, foot spas and creams; the inconvenience of additional hospital visits; and lack of benefit gained over the 12 month treatment period. Referring to the MRC framework, the findings from RheumAFooT suggest that further phase I modelling is required as well as refinement to the design of a definitive trial.