Discussion
We have developed a first international consensus statement on the management of endometriosis through rigorous methodology. An obvious finding in the quest for a consensus statement is that unanimity from a range of experts in any statement is difficult to attain. In our survey that followed the consensus meeting, none of the statements made achieved 100% agreement without the expression of a caveat about either the statement or the strength of the statement, and only 7 of our 69 consensus statements were associated with a 0% disagreement rate from the survey respondents. However, in the case of only two statements, we were unable to achieve a majority consensus.
The strength of this consensus statement is that it is truly international, with a breadth of representation from six continents across medical, surgical and fertility organizations, including a voice for the women themselves via 16 involved endometriosis organizations. There are potential weaknesses in a consensus process such as this. Some of our statements are not strongly based on research evidence and were termed GPPs; however, such statements could still be associated with a strong consensus amongst the group of experts. We will inevitably have overlooked some interventions that could be relevant, in spite of the methodology and feedback from all participants. It is therefore intended that this consensus will be updated regularly in response to feedback and, hopefully, increasing evidence in our field.
Unsurprisingly, there are similarities in our consensus statements with existing guidelines for managing endometriosis, but also the kind of differences that might be expected from the coalescence of an eclectic group of experts from many different standpoints. One of the real values to the participants in such an exercise is the opportunity to recognize a completely new perspective and interpretation of existing evidence; this can be applied in any multidisciplinary setting, where specialists in medical, surgical and fertility treatment join forces with women affected by endometriosis. In some cases, the strength of our statements (and in some cases, even the GRADE score) or the content of statements themselves conflict with those in other guidelines. We endeavoured to make strong statements (i) where the evidence was moderate or strong, in other words derived from reliable and reproducible RCTs (and even in some cases where the evidence was insufficient or negative where such evidence was deemed strong) or (ii) where the risk or expense of an intervention strongly justifies its non-use in the context of marginal or insufficient evidence or (iii) where there was enormous potential for benefit from a simple, low-invasive, low-cost intervention, to overcome a substantial burden of suffering, even in the face of only weak or absent research evidence (as in the case of our GPPs).
It must be emphasized that our process differed from that of guideline development. There is no general consensus on the most appropriate methodology for consensus statements and so we have adopted the methodology for the GRADE system of grading the quality of evidence (Guyatt et al., 2008) (now felt to be the most relevant method of grading evidence and recommendations in guidelines) and adapted this to our consensus process. The turbulence that is present in the normal clinical environment is reflected by the fact that there is much lack of consensus amongst experts surrounding all aspects of the management of endometriosis. This also reflects the fact that the reality of the clinical situation at an individual level is far more complex than the idealized situation in an RCT. It must also be acknowledged that a consensus statement from international experts would almost certainly be subtly different with a different group of experts, although it is hoped that our broad sample of individuals was representative of the spectrum of viewpoints of all the members of all the organizations and societies represented.
Key issues that we have few answers for are management of the adolescent who has, or might have, endometriosis (more research is required and focus needs to be applied to management algorithms for young women and adolescents) as well as intervention strategies in the younger age group designed to prevent endometriosis; lifestyle and dietary interventions (where research evidence is largely absent); standardization of long-term strategies for prevention of recurrent endometriosis; clarification of management strategies, both surgical and medical, for women with deep endometriosis; development of standards of experience and expertise required for surgeons undertaking advanced laparoscopic endometriosis surgery; standardization of centres/networks of expertise with regard to definition, accreditation and longevity; development of models of care in low-resource settings and understanding endometriosis and its potential treatment after menopause. We have not addressed the important issue of diagnosis and classification of endometriosis, which would benefit from a similar international consensus approach. Individualization of every woman's care is an important factor in long-term management. Furthermore, it is possible that a subpopulation of women with endometriosis (depending on age, impact of symptoms, severity of disease, current or future fertility wishes, lifestyle factors, previous treatments and possibly disease markers) will benefit from some form of medical treatment to alter the course of this condition longer term (Vercellini et al., 2011); the challenge is to identify these subpopulations and long-term management strategies. Further assessment of emerging therapies is also a key factor and this has been much neglected in recent times. It is of concern that, although many pre-clinical studies have shown positive results, very few have progressed to become phase II/III clinical trials, let alone proved to be effective (Guo et al., 2009). In 2009, of 15 registered clinical trials in endometriosis, listed as completed, only three had been published, whilst the remaining 12 (80%) were unpublished (Guo et al., 2009). More systematic and coordinated research effort and funding is required at an international level, so that any breakthrough treatment does not remain elusive, nor any research effort is ignored in order for others to continue to build upon results, be these positive or negative.