A PROPOSAL TO ESTABLISH A GLOBAL
DIVING AND HYPERBARIC MEDICINE CLINICAL TRIALS NETWORK


DRAFT DOCUMENT MARCH 2017



Executive summary
This document outlines our proposal to set up a global clinical trials network. The aim is to foster meaningful clinical trials in diving and hyperbaric medicine.
Interested parties are invited to consider this proposal and make any response they wish. All comments gratefully received. Participation is of course entirely voluntary.
Following written comments our aim is to discuss the proposal in face-to-face discussions at major international meetings and the intention is to have an organisation in place with a forward plan by the end of calendar 2017.


Introduction
This document outlines a proposal to establish a global research network to support clinical research in the areas of Diving and Hyperbaric Medicine (DHM). Such a research network would be based on a similar model used by many national research networks in other fields.
Our initial proposal is to establish a working party to set the structure, goals, membership and timeline and agenda for the Diving and Hyperbaric Medicine Global Clinical Trials Network (DaHMNet).

The Global Problem for Diving and Hyperbaric Medicine
The two fields present different problems and these will be dealt with separately.

Hyperbaric Medicine
Many practitioners note that our field continues to have a great deal of trouble entering what one might call ‘mainstream medicine’. Despite the best efforts of great pioneers in the field, we simply do not seem any closer to widespread acceptance from either academic institutions or even our professional colleagues. There are very few of us who have not faced significant opposition to any use for oxygen at pressure from insurance companies, national funding bodies, hospital administrations or specialist medical colleagues – despite an increasingly impressive evidence base and an increasing understanding of mechanisms at a molecular level. Many of us are frustrated and some are despondent. Despite considerable expansion in facilities in some countries (notably the USA), the field is under increasing financial constraint and pressure to narrow our base of indications. In others, the development of the field is stalled at a small number of active units with no sign of any plans for expansion into hospitals with a similar patient population.
But that is not the whole story. In parts of the world, HBOT is a well-accepted practice. In places like China and Russia, the ‘accepted’ list of indications is hundreds of diagnoses long and HBOT is widely accepted as an important adjunct in many mainstream medical regimens. To ‘Western’ eyes, many of these indications seem without coherent mechanistic or clinical basis. Increasingly, hyperbaric physicians in these countries are keen to produce high quality evidence to back up their vast clinical experience. This represents a unique opportunity to our field. We have high quality researchers in one part of the global community and very large clinical loads in another. One possibility of the proposed DaHNet is to bring these two groups together.
The problems with Hyperbaric Medicine
Any attempt to improve legitimacy will need to address some or all the elements that conspire to keep us in our current position. Some of those we have identified are:
  • Western pharmaceutical bias: Most of our colleagues as individuals, as well as our systems of medical finance, are based in either surgical or pharmaceutical-based therapeutics. The non-pharmaceutical therapies are largely non-medical – and even sometimes quite ‘alternative’ or discredited: physiotherapy, psychology, massage, chiropractic, acupuncture, homeopathy and naturopathy are some examples. Hyperbaric is often conceptualised as part of this non-medical culture and regarded with suspicion.

  • No hyperbaric included in the medical curriculum: It is very unusual to find any consideration of either diving or hyperbaric medicine in the standard curriculum at medical school. This lack of exposure speaks to HBO as a somewhat illegitimate therapy without scientific basis.

  • A history of famous charlatans in the field: From Orvil Cunningham and his steel ball hotel chamber in Kansas in the 1930s to some colourful contemporary characters promoting hyperbaric oxygen as a panacea for all manner of ills, every media report of another snake-oil salesman drives another wedge between ‘legitimate’ and ‘fringe’ medicine in the eyes of the former.

  • Disproof of high profile indications: From time to time, individual indications have come to the attention of mainstream practitioners based on some promising clinical evidence, only later to be disproven in larger, blinded randomised trials. One such condition is Multiple Sclerosis – case series and an early positive RCT suggested a benefit in both the reduction in symptoms of MS and slowing of disease progression. This (to their credit) drew the attention of neurologists interested in the area and resulted in a series of RCTs, the great majority of which suggested little or no benefit. As the disappointing results of these trials was disseminated, most practitioners who had become interested withdrew that interest. Eventually, the use of HBO to treat MS becomes another piece of evidence that ‘proves’ HBOT has no real medical use.

  • Patchy clinical evidence: Perhaps our greatest single problem is a lack of high-quality clinical evidence that unequivocally supports the use of HBOT. There are some indications where most hyperbaric physicians believe experience and modest levels of evidence make further investigation unnecessary or even unethical. This is a defensible position, but of little use if the mainstream of medicine rejects this justification for practice. For other indications there is a demonstrable lack of good evidence that needs to be addressed. The barriers to doing good clinical research in this area is the subject of another section of this proposal.

  • Loss of prominent pioneers: Many pioneers in the field came to the idea of HBO from the position of being legitimate, well-respected members of their own specialty. Such pioneers could bring some degree of legitimacy with them. As these pioneers have been replaced over the years with others brought up within the field itself, such respect from colleagues in other fields has tended to fall away.

  • Lack of a specialist practitioner model: There is no jurisdiction in the Western world where hyperbaric practitioners have a clear specialist practitioner status. In the USA, for example, many come from other ‘primary’ specialties and later develop a passion for DHM. The native qualifications in DHM are generally not of accepted specialist status or administered by a specialist group from another discipline (e.g. Occupational Medicine).

  • Skepticism about a therapy that does not require medical registration: In many juristictions, HBO can be administered under the direction of anyone – no qualifications are required. For many medical practitioners this is simply confirmation of a worthless treatment.

  • No money in it from industry sponsors: Oxygen is very cheap and chambers only required in small numbers to date. There are no significant sources available to sponsor large and well-constructed trials in the area

Diving Medicine
Diving medicine suffers less from poor perceptions of legitimacy. Most colleagues in the wider medical community seem happy to accept that the prevention and treatment of dysbaric diseases are legitimate (albeit ultra-specialized) medical pursuits. However, this general “acceptance” within the medical community has not translated into strong levels of research effort in areas that would seem fundamentally important. For example, there is only one randomized controlled double blinded trial of any intervention in the management of decompression illness. Indeed, there is a conspicuous lack of high quality evidence for most of our preventative strategies and therapeutic interventions for various diving related medical problems. The particular problems associated with conducting diving medicine research are articulated below.
The problems with Diving Medicine
  • Lack of funding for research: It is extremely difficult to obtain competitive public research funding for studying the complications of a recreational activity whose participants are mainly middle class males with moderate discretionary spending power. Moreover, as with hyperbaric medicine, there is limited benefit to potential industry sponsors and declining numbers of such (potential sponsors). The hey-days of diving medicine research corresponded with a period of heavy use of divers by offshore oil exploration and drilling companies, but this has declined as many underwater construction / inspection activities have been devolved to remote operated vehicles.

  • Distraction of potential researchers by other career activities: It is virtually impossible to build a clinical or science career based solely on diving medicine; particularly on the clinical side. Examples of positions which involve enough clinical diving medicine activity to occupy a physician in full time activity are extremely rare (perhaps non-existent). The vast majority of doctors involved in diving medicine have another clinical specialty. Most who combine diving with hyperbaric medicine would still find that the majority of their work is hyperbaric rather than diving medicine. Some militaries maintain positions in both clinical diving medicine and / or diving science that approximate full time jobs, but the occupants of these jobs often cycle to other assignments periodically.

  • Low and declining numbers of clinical cases for research: There is a very strong signal in the diving medicine literature that numbers of decompression illness cases are declining world-wide; substantially so in some locations. The reason for this has not been definitively established, but it may related, at least in part, to declining diving activity. Add to that the fact that the majority of cases that do occur are relatively mild and potentially spontaneously resolving and you have a milieu in which it is very difficult to perform studies investigating benefit of a therapy for serious cases. This is arguably one of the of the challenges that a clinical trials network is best suited to overcome.

  • Declining numbers of diving medical facilities: The provision of a hyperbaric unit that is able to comprehensively respond to a diving medical emergency 24/7 is very expensive, and as implied above, largely without financial reward. It is not surprising that many hyperbaric units that previously offered treatment to sick divers are now no longer doing so; particularly in the USA. This is resulting in further narrowing of the pool of potential researchers and facilities in which research may take place.

  • Fragmentation of effort resulting in small underpowered studies. Given the milieu described above, it is not surprising that many studies in diving medicine are conducted by groups operating in isolation, involve small numbers of subjects, and are consequently prone to statistical error.

Clinical Trials Networks
Clinical trials networks seek to improve the evidence base of a specific field or diagnostic category by supporting high quality multicentre research, and collaborating with other research groups. Research is often prioritised into efforts most likely to improve the quality and safety of medical practice.
Members of the DaHMNet will include dedicated researchers who are highly skilled in the theory and practice of research methodology and have a record of success in the coordination, conduct and management of large, multicenter, randomised controlled trials. Some will have had considerable success in attracting both industry and national research grants.
CTNs are about accumulating experience and wisdom concerning trialling, as well as empowering younger or inexperienced researchers to learn the ropes while assisting in meaningful research that will change practice. Decision makers in health care are increasingly using high quality scientific evidence to support clinical and health policy choices, however the widespread gaps in evidence-based knowledge suggest systematic flaws exist in the production of scientific evidence, in part because there is no consistent effort to conduct clinical trials designed to meet the needs of clinical decision makers.(1)
Clinical trials for which the hypothesis and study design are developed specifically to answer the questions faced by clinical decision makers are called pragmatic or practical clinical trials (PCTs). The proposed DaHMNet will be specifically designed to generate such questions and set about the best way to answer them. As Tunis et al have outlined, the characteristic features of PCTs are that they:
  • select clinically relevant alternative interventions to compare
  • include a diverse population of study participants
  • recruit participants from heterogeneous practice settings
  • collect data on a broad range of health outcomes of importance to patients (my emphasis).
The supply of PCTs is limited because the major funders of clinical research do not focus on supporting such trials – particularly in DHM as discussed above. The development of good trials in DHM will depend on the development of a cooperative mechanism to establish priorities, marshal resources and prosecute such trials.

The Proposal
Put simply, I am proposing we organise a global CTN. Global CTNs are not common, but currently exist in some fields where national research institutions have found common ground. I believe our unusual circumstances justify this approach. Our field of research is relatively small and national organisations find it difficult to marshal the manpower and know-how to make things happen.


GCTN.png

Figure 1. Possible elements within the proposed CTN

The figure suggests a basis from which we can start to build the structure needed to make progress. I envision a core group, nominated/elected by individual national societies and limited to about 20 individuals. We will attempt to meet at existing ASMs around the world and develop a formal set of aims, mission statements and working structure. I believe that even without significant funding during the initial period, we can make contributions through the development of standardised HBO treatment protocols, sham protocols and ideal research methodologies. The development of widely accepted standards in these areas alone would be a very large step in the right direction.
The figure is very much a draft collection of ideas – all are open to suggestion and debate (including the name!). In this first instance, I am submitting this expression of interest to all major players in the area. I will feed back the responses to all who express an interest in seeing how things go.
Please take the time to forward this to members of your organisations who may have some interest in this proposal. If possible, consider who in your organisation would be the right people to continue communication about this proposal.


What do you need to do?
Please discuss this proposal within your organisation or your organisation’s research committee. Any comments gratefully received m.bennett@unsw.edu.au
I am available at any time to try and answer any questions you may have in relation to this proposal

Mike Bennett
Simon Mitchell

Reference
1. Tunis SR, Stryer DB, Clancy CM. Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy. Jama. 2003 Sep 24;290(12):1624-32.





BACK