Abstract
Commentary 1: Baljit Dheansa
Heyland et al. 1 are to be praised for the slow, systematic approach they have taken to try and answer what is a relatively simple question, but one that is clouded with enormous complexity. Many in the burns community would be keen to know if glutamine supplementation can reduce mortality in major burns and garnering a large number of patient participants is essential to help arrive at an answer. However, the paper also highlights some major issues in research and, specifically, burns research. There has been a lot of previous research which is of potentially doubtful benefit because of small patient numbers or trial design. Much of our research is sadly like this, with a lack of clear trial design, small numbers and often significant bias. The inevitable result of this is either having to ignore such data, or worryingly, such data being used as the basis of new treatment approaches which may, at best, not help patients or, at worst, potentially cause harm.
Burns treatment varies enormously between countries, services and even individual burns surgeons, with many being aware of the significant gaps in our evidence related to these treatments. However, as a specialty, we have failed our patients and our own specialty by not summarising these and then making positive efforts to address them in a systematic manner. Glutamine’s benefit is one of the questions we need to answer, but there are so many more: timing of surgery; effectiveness of antibiotics; diagnosis of infection; methods of skin cover; methods of wound debridement; first aid techniques; types of dressing; scar management; and so on. Although Heyland et al. should be congratulated on getting to this point in what is clearly a long and expensive journey, it is a shame that we, as a burns community, have failed to show such rigour for much simpler and arguably easier to conduct trials in burn care. They are not alone, and many in burns research are trying very hard to do exactly this, but we have a long way to go and we need much more coordination in our approach. Without this, we will be guilty of conducting poor-quality research that engages patients, benefits no-one, uses funds that could be better utilised, and causes confusion or distracts from more robust research.
We desperately need to have a national programme of research that identifies important gaps in our knowledge, prioritises them, helps support trial design and then supports trial recruitment. This approach would mean poor research is unlikely to be funded, so any studies that are undertaken are more likely to benefit patients and that as a specialty we can ensure wide participation. If we are to obtain the best possible evidence, we also need to be mindful of the need for reproducibility and have even higher thresholds for statistical rigour. Having data that can be reproduced in the real world after a trial is essential; we need to ensure that what works in strict research conditions works in the real world. Ongoing audit of new approaches should be part of our practice. We need to be especially cautious of any trials that have been commercially funded. As for statistics, we all know the challenges many have in interpreting them, meaning that often many clinicians may not be fully aware of the limitations of the data presented. It behoves us to insist on much more clarity on statistical analysis, to allow clinicians to make appropriate decisions on the evidence presented. The cost of the RE-ENERGIZE trial is substantial, and it needs to be, to ensure that it is conducted as well as possible. Such funding could potentially have also supported a number of smaller, but equally beneficial, trials instead. How we direct funding in burn research will ultimately allow us to raise our standards, avoid less beneficial research and benefit our patients through more robust evidence-based treatments.
Commentary 2: Ciaran O’Boyle
The RE-ENERGIZE team, from Canada, are to be applauded for their efforts in bringing their idea to trial in a large, well-powered, study looking at glutamine supplementation in burns. 1 Burns is a field of study that has traditionally suffered from a perception by researchers and clinicians alike, of a lack of homogeneity among patients. To an extent, this perception is correct. However, the literal visibility of burn injuries and their visual impact upon observers might persuade researchers that patients are more heterogeneous than they actually are. Hypertension is often thought of as a homogenous entity. However, causes of heterogeneity in this group may be hidden and therefore unappreciated. In burns research, the fear of this heterogeneity has led groups to shy away from testing fundamental hypotheses that might produce answers which save or improve lives. As a result, burns research groups have often been satisfied to produce conspicuously weak evidence and then view that as achievement. It is highly refreshing and encouraging to see a research group approaching a clear question in burn care, with an absence of fear and the inhibition that this creates.
The group has set out their question clearly and has set outcomes that are achievable. Some may argue that the question and any conclusions will be excessively narrow. This view is wrong. The incremental increase in well-founded understanding has marked the broad ascent of medical knowledge for many years. Burn care and burns research has merely lagged behind the rest of the field in this respect. Other research teams in burn care should take heart from this group’s efforts and direct their energies to formulate good specific questions, create logical hypotheses, devise robust methods to test those hypotheses, involve colleagues in other interested groups (over 90 centres involved in the RE-ENERGIZE trial) and, above all, to have the determination to persist with good study plans, in order to push these through to the study phases, so that everyone everywhere can benefit from their findings.