Synthesising the entire body of systematic review evidence for a pain relieving treatment. How hard can it be?

In a previous blog, I discussed challenges faced when trying to evaluate whether treatments relieve pain. I described a review published in the journal Medicina where I critiqued factors influencing long-standing uncertainty about the effectiveness of transcutaneous electrical nerve stimulation (TENS) for relieving pain. This week our team published a follow-up paper that synthesised the entire body of systematic review and meta-analysis evidence on the effectiveness of TENS. We were the first team in history to attempt this mammoth task and I congratulate our long-suffering team members who saw the project through to completion: Dr Carole Paley, Dr Gareth Jones and Dr Priscilla Wittkopf.

How hard was it?

The project was funded by a grant from GlaxoSmithKline and has taken us two years to complete. During that time there has been a global pandemic, two members of our team have switched jobs and the majority of the project had to be conducted ‘remotely’. I liken the experience of synthesising the entire body of evidence to deep diving into a swimming pool and losing sight of the water’s surface. We found ourselves drowning in data, disorientated by Excel and Endnote databases, and entirely detached from the outside world. At times we were worried that we could not hold our breath any longer and wanted to ‘throw in the towel’. Somehow, we saw the project through to the end, and our reward is a 100-page published report citing 358 references that we hope will be used to anchor researchers in the field. Success in research is all about tenacity!

What did we find?

Our comprehensive appraisal involved a structured literature search; screening of over 600 abstracts and full reports against eligibility criteria and extracting, managing and analysing data from 169 reviews. A tally of authors’ conclusions suggested benefits from TENS in 69/169 reviews, no benefit from TENS in 13/169 reviews and inconclusive evidence in 87/169 reviews. There were 49 meta-analyses, but we judged only three of these to have sufficient data to be confident in their findings; TENS reduced chronic musculoskeletal pain and labour pain, and TENS lowered analgesic consumption post-surgery.

What do the findings mean?

We concluded that TENS should be considered as a treatment option, but the evidence was suggestive rather than compelling. Logic and reason dictated that we would get a more confident answer by synthesising the entire body of randomised controlled clinical trial evidence. The quantity of this evidence dwarfs our appraisal of systematic reviews.

What do we do next?

Our team laughs in the face of pain associated with large complex evidence syntheses, so we’re up for the challenge. Research projects are much like running marathons. At the end, you say you’ll never do another one. Yet, before you know it, you’re on the starting line asking yourself why you have committed to doing it again? We formally named this next project the ‘Meta-TENS study’ although colloquially we have been calling it the ‘Mega-TENS study’. We hope it will be a landmark study and have been working diligently on the data analysis for two years. We have submitted a report of our findings for publication and have been asked to make some revisions. We have just submitted the revised report and are holding our breath for a decision. Watch this space for the outcome, irrespective of whether it is positive or negative.