Thread by @graham_boniface

A thread about our new paper…

A systematic review exploring the evidence reported to underpin exercise dose in clinical trials of rheumatoid arthritis

academic.oup.com/rheumatology/a…

#exercise #rheumatoidarthritis #clinicaltrials
@RheumJnl @thecsp
1/

In the UK exercise is recommended by NICE alongside pharmaceutical interventions for the management of RA. Strengthening exercise is commonly used to counter the cachectic effects (muscle wasting) due to the disease. As with most things, dose is likely to matter 2/

Clinicians are encouraged to be evidence-based. RCTs are seen as one form of evidence that may be used to support clinical practice. However, have you ever wondered how researchers underpin the dose they prescribe in their trials? So did we, so we systematically looked... 3/

Drugs trials commonly employ pilot studies as an essential step to safeguard participants and to optimise dose/ potential for efficacy. The MRC framework for developing for complex interventions recommends piloting for addressing key uncertainties: LIKE DOSE! 4/

Using strengthening exercise in RA as a test case to explore how dose is underpinned in trials, we set about answering the following objectives: 5/

1/Determine what proportion of published RCTs evaluating strength-based exercise interventions in RA report using phase-I/II trials for setting dose parameters.
2/ Determine what type and level of evidence is used to underpin dose parameters. 6/

3/Explore the quality, consistency and applicability of the evidence used to underpin dose parameters.
4/Narratively explore if a relationship exists between risk of bias for RCTs evaluating strength-based interventions in RA and the level of evidence underpinning dose. 7/

We did all the important systematic review stuff. But being different, we searched the included RCTs underpinning evidence used to support dose. We then investigated the quality, consistency and applicability of that evidence. 8/

We searched 6 databases going back to the year 2000. 4382 records were identified and 32 RCTs were included for review. Only 4 (12.5%) RCTs reported piloting their intervention. None reported using dose-escalation methodology, commonly used in early drug trials. 9/

Only 12 (37.5%) RCTs cited any underpinning evidence to support dose of strengthening exercise. When investigated, the quality of that evidence using the OCEBM Levels of Evidence tool varied. 10/

We explored whether the RCT used the same dose as described/recommended by the underpinning evidence. Often the dose used was quite different to that recommended. We also found many parameters not supported by any evidence. 11/

We assessed how applicable the underpinning evidence was in relation to RA, gender and age. More than 50% of the time, the underpinning evidence used wasn’t really applicable. 12/

We explored whether we could identify if a relationship existed between the RoB for the twelve RCTs and the judged quality (level of evidence) of the underpinning evidence. 13/

Whilst too few studies for statistical analysis, RCTs with high/unclear RoB had underpinning evidence rated as unclear or incorrect (e.g. not relevant to strengthening exercise or the reported evidence was cited incorrectly). 14/

This is the first systematic review that we are aware of to explore in detail the underpinning evidence used by healthcare researchers to justify the prescribed dose of strengthening exercise used in clinical trials of RA. 15/

The lack of formal piloting highlighted by this review suggests that current practice in the field of RCTs using exercise-based interventions in RA rarely aligns with the MRC framework for the development and evaluation of complex interventions 16/

The evidence that is used to justify dose parameters (when used) is often not very appropriate or does not support the reported dose parameters. 17/

So what are the implications? We already know we need to improve not only the standard of reporting related to exercise interventions thanks to fantastic work led by @Tammy_Hoffman , but also the evidence they use to justify their decisions about what dose to prescribe. 18/

Funders and peer reviewers should take a careful and critical approach when considering how exercise dose has been formulated. 19/

Pilot testing using dose escalation methodology may help answer uncertainties about what dose works best. The implications of this would necessitate funders considering more funding and time to support researchers in generating the preliminary data before the definitive RCT. 20/

Our findings offer an opportunity for positive change. Improving practice in development maximises the potential for exercise interventions to deliver benefit. 21/

Addressing these weaknesses may contribute to better quality research being conducted and reducing research waste in exercise interventions 22/
THAT’S ALL FOLKS!

PS. We totally poached the idea of this tweet thread from @marinuswinters ‘ great example.

https://twitter.com/MarinusWinters/status/1270946274599206912?s=20

Great ideas catch on! Thanks Marinus,