Clinical Trial Registration(a regulatory hinderance or a help?)

Welcome! Another blog appears at last …

One of the dental trials I am currently working on is being carried out in several countries (we are in the process of getting it off the ground here in the UK). The trial is a comparison of different treatments for decay in children’s teeth and their outcomes.
I've been challenged by a couple of my fellow researchers to justify one of the particular aspects of trial beaurocracy - Clinical Trial Registration - that I have suggested is important. Although widespread in medical trials (especially for trials of medicinal products), it's really not really the norm yet to register dental trials.
Often, the bureaucracy associated with setting up and running clinical trials (although necessary) is often seen as a hindrance, especially as it’s a bit of a ‘one size fits all’. So no allowance is made for trials comparing two ‘standard’ non-dangerous treatments as opposed to those testing a ‘new’ treatment with unknown and potentially damaging side effects.
However, rather than being a hindrance, Trial Registration is actually one of the things that is a help. It's an international move that has been encouraged from a number of fronts. The idea behind obligatory registration of all clinical trials (drugs, devices, surgical procedures, dental treatments etc etc) is to create a publicly available database of trials being carried out. But really - why bother? Well, I'm going to have a stab at that justification to my co-researchers now...

Publishing

Many biomedical, and a very few dental, journals do require a trial registration number for manuscript publication in line with the International Committee of Medical Journal Editors 'Uniform Requirements for Manuscripts Submitted to Biomedical Journals'. So after completing your trial you could find that you can’t publish your findings in certain journals without a prospectively registered trial number. In dentistry/ oral health, these journals include BMC Oral Health and Journal of Dental Research (I know from personal experience that both these journals insist on a trial registration number being submitted before a research article on a trial will be accepted for peer review). The British Dental Journal is registered on the ICMJE website as following the Uniform Requirements, but there is no evidence of it in their author guidelines and unfortunately, clinical trial registration numbers are not visible in the published RCTs I looked at. There are other journals who state that they are signed up, through the Uniform Requirements, to these high standards of publication that we should be (as researchers) not only striving to reach but driving upwards. However, despite this signing up process, it seems that some journals are poor at ensuring that such things as CONSORT is adhered to for RCTs, conflicts of interest are disclosed and overlapping publications are clarified. I think we have some obligation as researchers and the users of the journals to help make these things a standard part of our manuscripts.

Future proofing

As we all know, trials take an absolute age to set up, carry out well, follow up and then publish the findings of.  Standards in publication in dental journals are improving (reporting guidelines such as CONSORT are slowly becoming more widely used).  Should journals that we might be expecting to publish in, have a change in editorship or policy, and the Uniform Requirements for Manuscripts Submitted to Biomedical Journals be adhered to, it would be wise to be prepared.

Transparency

Registering your trial makes it more visible and means that if someone else wants to do the same trial or a similar trial to you, when they check on the standard clinical trial databases before starting theirs (or when their funding body do), they will see what you are doing and may request to join forces, improving the generalisability of the trial.  Alternatively, they may decide their work is unnecessary (and thus avoid patients being pointlessly entered into a trial that you are going to find the answer to anyway!).  The other advantage of visibility is that if someone is going to do a similar type of trial, they will be aware of your expertise and can contact you to help avoid the pitfalls you will no doubt have encountered, find out what worked well in terms of outcome measures, patient preferences etc and maybe use similar tools to enable comparisons between trials (something that is currently pretty poor in Dentistry).

Overlapping publications

When the trial registration number is attached to the end of every manuscript associated with that trial, it means that readers will always know the data (whether it's different datasets or similar datasets at different times), all came from the same trial.  It also makes life much easier for those of us undertaking systematic reviews.

And last but should really be first – Patients

One of the (perhaps future) benefits of trials being registered on a publically accessible database is that patients can see the kind of research being carried out in Oral Health and Dentistry.  This helps raise awareness of what is available to them or at least, what we are testing to try to improve treatments.  This can only help the informed dialogue all clinicians should be having with patients/ public about treatment options.

If you are peer reviewing a paper for a journal then and it’s a prospective clinical trial, check to see if it’s been registered anywhere, and if it has, check that the authors have stuck to their original stated aim.  Also, if the journal you are reviewing for is registered with the ICMJE, as being signed up to the Uniform Requirements, check that they are encouraging authors to adhere to these standards.  Although it will take time, this will help to improve the quality of the trials in dentistry and therefore ultimately the care we provide for our patients.

 

There are a number of different trials registries which are acceptable to the ICMJE including: www.anzctr.org.au, www.clinicaltrials.gov, www.ISRCTN.org, www.umin.ac.jp/ctr/index/htm, www.trialregister.nl, https://eudract.ema.europa.eu/ and although some have a cost attached, others don’t.

Evidence based dentistry or exclusive based dentistry?

Hello, and welcome!

I'm planning to blog here about dentistry, evidence, research, teaching, patient care and other stuff.  Hopefully it will be of interest to someone and if not, maybe just by getting some of this stuff down on e-paper it will be (at the very least) fun to feel like I'm sharing some of the amusing stuff and maybe it will stop me feeling so narked about some of it!

Please forgive any inaccuracies (and let me know about them), they are unintentional...

Let's just start with last week - well last week was a funny old week.

Evidence-wise, it began with a Sunday Times article on the Hall Technique (and mentioning the FiCTION Trial ) being picked up by several other papers (Daily Mail Deccan Herald and Topnewshealth).  The numerous inaccuracies were despite my best efforts to send information that was short, to the point (uninflammatory!) and accurate.  This is something we apparently just have to live with; there is no way of seeing these articles before they are actually out in the public domain.

But what does it matter?

Well, I think it does.

Take the Hall Technique (since I know it well!), and yes, since you ask, I probably am biased as I have researched it but I try to present the evidence with (as Ben Goldacre would put it) sunlight on it,  we are asking dentists to consider changing their practice and seal in decay.

Here are 2 perspectives:

The general public's point of view.  A look at the comments at the end of the Mail online article linked to above, shows the limited understanding people have of what is actually going on in their mouth when we're 'doing' dentistry.  Here's just one of these comments:

"Sealing in bacteria is a recipe for a health disaster! We already have root canal work doing the same thing - infection sealed in seeps bacteria into your blood stream and will attack the heart in particular! A decaying tooth is decaying because of bacteria - there is huge amounts of research indicating just how dangerous that can be!"

Yes, it's anecdote and I've picked it out particularly, but it is difficult for us to imagine we can suddenly jump into full blown Evidence Based Dentistry and expect our patients to have a deep and considered understanding of why we might consider changing our practice, especially with something we've been doing for a long, long time (I think it's around 150 years that we've been getting decay out of teeth one way or another before plugging the hole with something).

Taking the evidence into practice idea further and some of the barriers (this time from the profession's perspective) - I was given, today, a copy of an editorial from the American Association of Paediatric Dentistry by the CEO of the AAPD called "What Distinguishes the United States".  It follows on from a joint meeting in September between the AAPD  and the Royal College of Surgeons in Edinburgh.  By all accounts the meeting was a great success and there was much sharing of ideas.  But Dr John Rutkauskas says

"Yes, we know that bad British and Scottish teeth is a good joke, but it is not an unfounded stereotype"

(Just a cheap jibe and of no real consequence).  What is interesting is that he dismisses the idea of sealing caries into teeth saying:

"Can we imagine informing our parents that we are placing a crown over an untreated, decayed tooth...".

 In the AAPD society's journal a systematic review of partial caries removal in primary teeth expresses this perspective well, with the text:

"Since the maintenance of carious tissue beneath restorations after partial removal of demineralized dentin is still seen with caution and skepticism by most professionals, the objective of the present review was to discuss the rationale for the use of this technique as an alternative for the control of dentinal caries in primary teeth."

(Ribeiro CCC et al. Pediatr Dent 2012;34:39-41).  Ribeiro's conclusion will come as no surprise to cariologists and falls in line with a growing number of systematic reviews, all pointing in the same direction:

"The favorable outcomes of partial caries removal in a single session support the indication of this modality as a definitive alternative restorative treatment for the primary dentition."

As healthcare providers, we have a duty to see beyond our prejudices and consider the evidence and its relationship to our patients wishes (and in the case of children their ability to cope with different treatments).  So when 39% of children with Early Childhood Caries, who have had a general anaesthetic to have their dental treatment carried out, require further treatment within a year, (Pediatr Dent 2012;33(7):510-514), perhaps those authors' conclusions

"The R rate (39%) observed is consistent with earlier reports.  Novel approaches are needed to improve relapse prevention".

should resonate more strongly than they are likely to, if history is anything to go by...

PS I promise I will not blog about the Hall Technique incessantly!!!!