Wednesday, October 12, 2016

Why Prescribe Rivaroxaban?

First things first: I have no conflicts of interest regarding the content of this blog entry; I'm merely sharing my best interpretation of the published literature as I'm aware of it.

Rivaroxaban (Xarelto) has become the most widely used oral anticoagulant in America. Choosing one NOAC to primarily use is a good idea because one can become familiar with its dosing requirements and drug interactions and prescribe it well. This is especially true for primary care practitioners who are faced with a constant barage of new medications with which to become familiar.

But why choose Rivaroxaban?

There were three pivotal trials comparing warfarin to each of the three non-vitamin-K-dependent oral anticoagulants (NOACs) currently available in Canada: RE-LY for dabigatran, ARISTOTLE for apixaban, and ROCKET-AF for rivaroxaban. Each of those trials established the superiority of its respective NOAC over warfarin in either effectiveness (reducing stroke and systemic embolism) and/or safety (reducing major bleeding) except for one. That's right: In ROCKET-AF, rivaroxaban was merely "non-inferior" to warfarin.

It is difficult to compare the outcomes across these trials because the populations were all different, but consider this: ROCKET-AF included the highest risk patients with the highest rates of the primary outcome (stroke and systemic embolism),  placing it in the best possible position to demonstrate statistical superiority in efficacy if it was present, yet it didn't. Not only that, warfarin-treated patients in ROCKET-AF had the lowest mean time in the therapeutic range (55% in ROCKET-AF vs approximately 62-64% in the others). That means that rivaroxaban was tested against warfarin performing at its worst among these three pivotal trials, and it still couldn't come out ahead even though the others did.*

While a head-to-head comparison of the NOACs will probably never be performed (the number of patients needed to do such a trial would be truly enormous), there is mounting observational community based data that permits head-to-head comparisons of just how these drugs are actually performing in the "real world". Three such studies (available here, here, and here) have been published so far, and compared to dabigatran and apixaban, rivaroxaban has repeatedly been associated with higher rates of major bleeding and/or stroke & systemic embolism (SSE). One must be careful in interpreting these studies because the assignment to each drug is not randomized. Investigators use propensity scores to match patients for covariates that influence treatment assignment, but it is unlikely that all relevant covariates are able to be accounted for.  Accordingly, such information is to be considered hypothesis generating. Nevertheless, if one is to find one NOAC to prefer among the others, this data is enough to bolster the suspicion, based upon the pivotal trial results I described above, that rivaroxaban may not perform as well as its competitors.

There exists a ready and plausible explanation for the possible under-performance of rivaroxaban: its once-a-day (OD) dosing schedule. The half lives of rivaroxaban, apixaban and dabigatran are all around 12 hours, yet rivaroxaban is the only one available in Canada that has been tested in a once-daily (OD) dosing regimen. This has undoubtedly proven to be a marketing boon for Bayer, but only because most doctors over-estimate the compliance and adherence benefits of OD dosing versus twice-a-day dosing, which are small (please read the paper that Bayer researchers cite supporting their decision to use OD dosing). And besides, adherence among apixaban users is probably similar to adherence among rivaroxaban users.

What most prescribers aren't aware of when a drug with a half life of 12 hours is dosed OD are the consequences of missed doses and extra doses, which are subtherapeutic drug levels for prolonged periods of time (the equivalent of missing three consecutive BID doses of a competitor drug) or very high peak drug concentrations. I urge you to click on the link in the last sentence to view the paper, free-on-line, and study figures 1 & 2. It is well recognized that the safety and effectiveness of anticoagulants are closely related to the time spent in the therapeutic window, and so it may well be that by dosing rivaroxaban once-a-day, resulting in high peak concentrations, low trough concentrations, and markedly exaggerated swings when doses are accidentally missed or doubled, patients are actually being placed at unnecessary risk. And so it may well be that the consequences of the kinds of minor deviations from perfect compliance that most patients are prone to from time to time are greater for patients on rivaroxaban than its BID-dosed competitors.

I share this information with my patients so that they understand that I'm choosing to prescribe apixaban twice-a-day based on good evidence that it's both safer and more effective than warfarin. I explain to them that the twice-a-day dosing keeps them in the therapeutic window more effectively when the odd dose is missed or the odd extra one is taken. Pragmatically speaking, many patients with atrial fibrillation are already on other treatments that require them to take pills at least twice a day, so fitting apixaban into their medication schedule doesn't add to their frequency of pill-taking. Another pragmatic advantage of apixaban is that it is the least renally excreted NOAC currently available, so dose reductions are rarely required, and changes in renal function are less likely to cause bleeding. That also makes peri-procedural management of apixaban straight forward and easy to remember. Of course, if a patient refuses to consider anything other than a once-a day pill, then I prescribe rivaroxaban, and I'm careful to make sure that they know that they must take it with the largest meal of their day for proper absorption (a feature of rivaroxaban that complicates its implementation that is often overlooked by prescribers, in my experience).

Perhaps you disagree? If you do, please chime in in the comments section below. If I should be prescribing rivaroxaban more often, or apixaban less often, I'd certainly like to know.

*As if that wasn't enough, the warfarin assigned patients used a device to monitor their INRs at home, and Bayer and Johnson & Johnson (the makers of rivaroxaban) were aware that there were problems with this device underestimating the INR, potentially leading to more bleeding in patients on warfarin, yet they kept that information from the FDA.

Friday, August 12, 2016

Why I'll keep on flossing, thank-you.

You should floss your teeth everyday.

Knowing how much importance I place on evidence, and given the recent media hype spawned by a story by the Associated Press about the paucity of good quality evidence supporting that recommendation, you might be tempted to call me a hypocrite.

But you’d be wrong.

If you’ve been reading this blog, you’d also know that I fully recognize that we most often have to make decisions in the absence of complete or even good information (see here). And besides, as nice as it would be, we don’t need the highest quality evidence - multiple, consistent, well-conducted randomized controlled trials (RCTs) -  to provide a reasonable answer to every question.

So what is the state of the evidence regarding daily flossing? You could find that out for yourself – no media craze required – at the Cochrane Collaboration (which I’ve written about before here) who wrote:
"Twelve trials were included in this review which reported data on two outcomes (dental plaque and gum disease). Trials were of poor quality and conclusions must be viewed as unreliable. The review showed that people who brush and floss regularly have less gum bleeding compared to toothbrushing alone. There was weak, very unreliable evidence of a possible small reduction in plaque. There was no information on other measurements such as tooth decay because the trials were not long enough and detecting early stage decay between teeth is difficult."
And here's what they concluded:
"There is some evidence from twelve studies that flossing in addition to toothbrushing reduces gingivitis compared to toothbrushing alone. There is weak, very unreliable evidence from 10 studies that flossing plus toothbrushing may be associated with a small reduction in plaque at 1 and 3 months. No studies reported the effectiveness of flossing plus toothbrushing for preventing dental caries."
It should be no surprise that there are no randomized trials reporting a reduction in cavities (dental carries) among flossers compared to non-flossers. Such a study would require that large numbers of subjects be randomized and followed for years (since it takes years for carries to develop). Large, long-term studies are costly and labor intensive, and that's why they haven't been done. Who's going to pay millions of dollars to do those studies? Are you willing to cough up some money for the cause?

Perhaps the industry that profits from the manufacture of dental floss should cover the costs, but why would they when the available evidence is enough to reasonably conclude that regular flossing prevents gum disease, which is really enough to recommend it? Even if that's all that it does, you should be flossing. Never mind that there isn't evidence showing that it prevents cavities.

This is an especially important question among people like me with valvular heart disease (VHD). Gum bleeding that permits oral microbes access to the bloodstream is an important cause of infectious endocarditis: a life threatening infection on heart valve tissue. Among the most common causative microbes are oral bacteria that get into the bloodstream by way of gum injury and micro bleeding that occurs throughout regular daily life (1,2).

When I was diagnosed with VHD about 4 years ago, I started flossing every day. Prior to that, I was like Margaret Wente (whose inflammatory piece in the Globe and Mail sparked my desire to write this post), which is to say that I only flossed a day or two before seeing my dentist, and when I did, my gums always bled. But since flossing daily, my gums hardly ever bleed, and haven’t bled at all at my last 2 dental visits. I’m living proof that flossing prevents gingivitis and there is plenty of other anecdotal evidence like mine to add to the already existent and reasonably good higher-quality evidence that it does.

Another widely reported anecdote that I can speak to: despite brushing twice a day, that string used to have quite a smell when I was finished, but after a few weeks in the habit, the foul scent was gone. Preventing bad breath is another terrific reason to floss your teeth daily, don't you think?

Now, one caveat: all of my comments refer to regular (ie. daily) flossing. Intermittently flossing and stopping will likely lead to more gum bleeding because the gingivitis that causes the underlying bleeding just returns in between flossing stints. That could actually be harmful, since everybody is at risk of endocarditis (though not as at high a risk as people with VHD). But other than that, the potential risk of daily flossing is almost certainly astronomically low.

Just as we don’t need a RCT of parachutes for jumping out of airplanes, we also don’t need anymore RCTs of flossing. As tempting as it may be - because I know how unpopular the idea of regular flossing is to most people - you should not mistake an absence of evidence (or a paucity of evidence, in this case) for evidence of absence. I'm sufficiently convinced that daily flossing is having a positive impact on my oral hygiene, and perhaps even to my overall health, and you should be too.

The stakes may not be as high for you as for me, and you may reasonably decide that a reduction in gingivitis is not worth daily flossing for you, which would be fine because you'd be making a decision based upon a reasonable and well-informed interpretation of the evidence. But please, do not make the mistake that Margaret Wente and others in the media have made, which is to conclude, because it's the conclusion that they like and/or that they think their readers will like, that we should all stop flossing because there is evidence that it doesn't do any good.

That would not be fine at all.

1. Lockhart PB, Brennan MT, Sasser HC, Fox PC, Paster BJ, Bahrani-Mougeot FK. Bacteremia associated with toothbrushing and dental extraction. Circulation 2008;117:3118–3125

2. Veloso TR, Amiguet M, Rousson V, Giddey M, Vouillamoz J, Moreillon P, Entenza JM. Induction of experimental endocarditis by continuous low-grade bacteremia mimicking spontaneous bacteremia in humans. Infect Immun2011;79:2006–2011.

Sunday, February 21, 2016

Post-Op, Part 2

My post-op left ventricular indices are:

Left ventricular diastolic dimension: 57 mm
Left ventricular systolic dimension: 46 mm
Left ventricular ejection fraction: 48%

I'm very encouraged by the dramatic reduction in the diastolic dimension, immediately into the normal range. Normal for me is another matter, but my LV can't shrink overnight. This reduction must purely result from having a competent valve; that is, from no longer having at least half of my enormous stroke volume rushing back into my LV. 

As Dr. Chris Simpson predicted over in the discussion at Facebook, the initial effect is seen mostly in the diastolic dimension. My systolic dimension actually increased a little bit. Accordingly, my EF dropped from 60 to 48%*, but I'm not in the least bit worried that this might represent any significant irreversible contractile dysfunction, and like Dr. Simpson, I also think that it has no known prognostic significance. 

Loading conditions are everything here, and my LV has suddenly been dramatically under-filled.

My aortic regurgitation had been significant for more than 5 years, probably more than 10, prior to operation. It's going to take years for my LV to remodel, and the available data is clear: given my LV size, if pre-op LVEF was normal, it's normal during follow up (excluding a peri-operative myocardial infarction or some other catastrophe).

As my LV physically shrinks (LV mass declines), I'm sure that my ejection fraction, which is close to normal now, will once again end up in the normal range. My read of the literature suggests that most of the changes happen in the first six months, but my surgeon told me to expect continued remodelling over 2-3 years.

It will never be the heart that I would have had without aortic regurgitation, but the available follow up data strongly suggests that it should be a heart that will last me a long time into the future without any specific anticipated problems.

Here's an interesting question for my medical colleagues: if you were me, and you knew that your post-op EF was 0.48, would you take any medication for LV dysfunction to try to help my LV remodel over time?  A beta blocker, perhaps? An ACE-I? Both? None?

*measured several times using different methods and matching visual estimates as well.

Saturday, February 20, 2016


When I was first diagnosed with severe aortic regurgitation, there was a great deal of disagreement about what to do. A significant majority of cardiologists and surgeons I saw recommended surgery within 6 months, while a small minority suggested that I could safely wait several years, perhaps even ten (or more), before requiring my valve operation.

As I wrote before, the advantage to early operation is that it minimizes the chances of waiting too long. At a certain point, as the left ventricle undergoes chronic volume overloading, irreversible contractile dysfunction develops, and I certainly didn't want to be left with a weak heart after surgery that would last the rest of my days. Not only that, we know that if one operates too late, survival is reduced.

The advantages to waiting are numerous. Firstly, it delays an event that has a mortality of about 1%. Secondly, it delays the onset of life with a mechanical valve, meaning that it delays the risks of valve clot and stroke, infection, as well as the risks of anticoagulation with warfarin. Thirdly, as soon as a valve is put in, a clock starts ticking until it will need to be replaced, too. The later one can operate, the higher the chances are that only one operation will be needed.

So whom to listen to among the disagreement was one of the early conundrums I faced after diagnosis. I decided to go with the available data which coincided with the opinion of the cardiologist most experienced in timing such operations, both indicating that I should not undergo surgery at that time but rather delay delay it as long as possible, possibly for years.

Well, after three years of following my heart size and function closely with serial ultrasound and MRI examinations, my ventricle showed clear signs of increasing in size just a little bit too much, and the opinions of all involved aligned: it was time to operate. Now we get a chance to see if my initial choice of waiting was a mistake, or not.

Three years ago, when I was diagnosed, the relevant parameters were as follows:
Left ventricular diastolic dimension: 63 mm
Left ventricular systolic dimension: 42 mm
Left ventricular ejection fraction: 54%

Pre-operatively, those parameters were:
Left ventricular diastolic dimension: 67-70 mm
Left ventricular systolic dimension: 44 mm
Left ventricular ejection fraction: 60%

What do you think those parameters are on my post-op echo? If my LV remains large and my function (ejection fraction) drops dramatically, then I probably made a mistake (though, to be fair, we must give my heart some time to remodel and get used to the new conditions of a fully competent mechanical valve). On the other hand, if my left ventricle has shrunk, and my function remains good, then we can only expect improvement over time, and I probably made the right choice to wait and enjoy three years without the burdens of a mechanical valve. (And they were three very good years.)

Chime in below with your predictions. In a few days, I'll reveal what the numbers actually are.

Sunday, January 31, 2016

Common sense is too common

The snow has finally stopped falling and you're pleased to be inside, driveway all shovelled neatly (first one on the block!), the aroma of a fresh pot of coffee permeating your home. Too bad for you that the squeezing sensation in the centre of your chest that kind of niggled while you were outside has just returned, but this time with a vengeance. Your wife calls 911 because the worried look on your face is actually worse than hers. What's the first thing paramedics will do when they arrive and learn that you're having chest pain? What's the first thing you probably want them to do?

Before even giving you an aspirin to chew, they'll probably strap on nasal prongs and give you some oxygen. After all, if you're having a heart attack, the problem is that the supply of blood, and therefore of good ol' oxygen, to your heart muscle is being choked off by a blood clot in a heart artery.

What could go wrong by giving a supplement of a natural substance that all our cells need to survive and of which those cells are being deprived?

Lots, apparently. Just click here to see the results of a clinical trial that randomly assigned 638 patients with chest pain to receive supplemental oxygen or not. Four hundred and forty one of them turned out to be having heart attacks and during followup, compared to those who just breathed ambient air, those who got the oxygen had larger heart attacks, more recurrent heart attacks, and more cardiac arrhythmias.

Traditional Chinese Medicine Store
Now just think, if oxygen turns out to be bad for you in the midst of a heart attack - a natural and "common sense" treatment given a basic understanding of the situation - what other supplements that are natural and appeal to common sense might be bad for you, too?

Supplement Store
The available data make a strong enough case to stop routinely providing supplemental oxygen to patients having chest pain and heart attacks. A time honoured treatment should no longer be employed. There is a long list of medical therapies established by common sense that are no longer offered because they've been shown in clinical trials to be ineffective or harmful (and it's an amazing list that you really should click on and see so here's another chance if you missed it before).

Tell me this: when was the last time that a supplement, herbal, or homeopathic treatment was tested by those practitioners in a clinical trial and pulled from the shelves?

Homeopathy Store
Another timely example of the failure of common sense is screening for cancer. If you have a test that can detect cancer, applying it to populations should reduce premature deaths. Simple, right? But the situation for screening is much more complicated than it seems and, in fact, screening the general population for cancer, including breast, lung, colon and prostate cancer, is probably a huge waste of time, effort, worry, and money (with the possible exception of pap smears for cervical cancer). Not only that, it probably causes more harm than good, and it's a practice that should stop. The same is true for the annual physical examination, which is going the way of the Dodo. Why? Because skeptical people put these common sense notions to the real test of randomized trials and the results weren't what common sense had predicted.

Common sense tells us that because something seems like it should work, it does work, but it's time to get humble, to became skeptical of common sense. It's time to admit that many things are far more complicated than they seem. I know that may make some people feel small and insignificant, but that's really not necessary. Evidence makes us powerful. Experts aren't necessarily smarter than you. Real experts just know the evidence better than others. By learning how to find and assess the evidence, you can become powerful, too. An easy way to get to the best understanding of the available health-related evidence is to use Cochrane, a global non-profit, non-governmental organization that you can read all about at Wikipedia here. Search your health query and Cochrane is your friend.

Voltaire said that common sense is not common. On the other hand, it seems far too common to me. In everything from philanthropy to economics, from politics to education, and beyond, what we need is less common sense, and more high quality evidence.

Saturday, December 26, 2015

Skepsis in 2015: An Index

The cliché has proven to be true once again: time flies when you're having fun. I can barely believe that this blog is now almost two years old, during which time it has received over 16,000 views from all over the world.

Given how poorly my predictions for post topics went last year, I won't be making any this year with one exception. Valve surgery in early February means fewer posts while I'm recovering and whatever I do get around to writing about will probably be more personal in nature, describing my peri-operative experiences.  I do still plan to continue to criticize theism and to provide some personal insights into medicine and cardiology. I also plan to participate in the Calgary Run for Water again on June 11, 2016, aiming for a personal best in the 10k with my new valve, whatever it turns out to be.

I hope that you'll continue to stay tuned and make some time in your busy lives to consider my posts. While they are often written for the personal benefit of refining and organizing my own thoughts, and to leave a trail that my children can one day follow to know how I tended to think about at least some topics, I nevertheless do try to write them for the benefit of others as well.

I hope that 2016 brings you good health and a wealth of experiences that will make you as happy and fulfilled as I have so far been in my life. In the meantime, here's how Skepsis went down in 2015:

In the wake of loads of bullshit that I was hearing by the regressive left after the Charlie Hebdo massacre, I thought that it was important to remember that What people believe really does matter.

I included less content by other writers this year than last, but two pieces that I thought perfectly expressed my own thoughts were by Gordon Gibson on Charlie Hebdo and a short video by Robert Lindsay on the critical importance of secularism.

Apologists for religiously motivated evil are often quick to suggest that science can also motivate evil behaviour, but I argued - decisively, I believe - that this tu quoque is incoherent in Did Joseph Mengele act "in the name of" science?. Thanks to an astute reader, I learned that much turns on the ambiguity of the phrase "in the name of", and so I clarified my argument without using it in a follow up post. I'm rather proud of these two posts: Later in the year, a very intelligent Facebook friend, doctor, and writer, admitted that they caused him to change his mind about this subject and that he would refrain from spreading this fallacious meme anymore.

I continued my critique of anti-vaxxers by identifying one key question that they should have to answer. 2015 saw legal support for vaccine exemptions face major challenges in North America. The amazing Dr. Paul Offit wrote a great piece on religious exemptions: What would Jesus do about measles?

In February, I shared the work of my friend in Edmonton, Alexander Delorme, who wrote about the Chapel Hill murders. The perpetrator has since been charged and will undergo a death penalty trial. Very little has publicly been clarified about his motivations, but the notion that atheism could have contributed is as incoherent as the notion that science motivated the Nazis. I suspect that his trial will show that, too.

In Should we accept revelation?, I argued that religious epistemology should be rejected because it is irrational. This spawned a 5-part series of posts on the epistemic impact of peer disagreement. I think that these are the most important posts I wrote this year.

In What if you could travel back in time? I challenged our fascination with youth. Most middle aged and older people who've considerd this thought experiment conclude that this is the best time to be alive.

The killing of Cecil the lion had me asking a question that nobody was, and everybody should have been: What trophy hunting is forcing my to ask.

This was the year that my left ventricle showed significant but subtle signs of enlargement leading me to pull the trigger and decide to have aortic valve surgery. In Decisions, decisions, I weighed the options before me and made a difficult, tentative choice.

My last two posts of the year challenged an idea that is commonplace among non-believers, namely, that believers have the burden of proof. But given what most non-believers do believe, this idea is a deepity, and it's just plain false. Thanks to my invitation by Justin Scheiber (of Reasonable Doubts fame) to act as a contributor to the Facebook page for Real Atheology, these were among the most viewed posts of 2015.

Friday, November 27, 2015

Atheism, Theism, And the Burden of Proof

I'm going to say something that should be uncontroversial among people who take pride in being rational: one's beliefs must conform with reasons for belief. Quite simply, this means that rationality itself places a burden of proof on everyone to have reasons for their beliefs. But a strange (and frankly, embarrassing) thing happens to many atheists when they enter into a dispute about the existence of God. Suddenly, atheists who would normally agree with what I wrote above, claim that the burden of proof lies squarely and only with theists. Apparently, according to these atheists, as soon as their belief is in question, the burden is entirely on the other side.

How do these folks support the claim that the theist has the sole burden? Their argument goes something like this:

Premise 1: The burden of proof is always on the claimant
Premise 2: Theists are making the claim that God does or probably does exist
Premise 3: Atheists merely lack belief in God's existence and, as such, are making no claim about it.
Conclusion 1: following from (1) & (2), theists have the burden of proof regarding the existence of God.
Conclusion 2: following from (1) & (3), atheists have no such burden.

This would be a valid and sound argument, and a very dandy one for atheists, except for one problem: the claim that atheists just lack belief in the existence of God is often misleading. It fails to accurately describe what most atheists usually think about the probability of God's existence, namely, that it's unlikely. Here's the rub: these atheists think that God probably doesn't exist, and that's a claim about the existence of God. It therefore follows from Premise 1 that they do indeed, have a burden of proof.

So who has no burden?
The only person with no burden regarding a claim is the person who hasn't had enough of a chance to think about the truth or falsehood of the claim and formulate a belief either way. If you haven't had a chance to really think about whether taking in Syrian refugees right now is a good idea, you could say that you "don't believe" that taking them in is a good idea, just as you could say that you "don't believe" that not taking them in is a good idea. You really don't know what to think. When in the psychological state of not knowing what to think about a claim, you really have no burden because you really are making no claim. Please notice that this position poses no challenge to a claim.

The atheists I'm addressing in this post often make the preposterous announcement that they lack belief in God the way a baby or a dog does. While it's true that babies and dogs haven't thought about the probability of God's existence, and therefore make no claim and assume no burden, I can hardly see why atheists would want to bring agents that lack the cognitive abilities to even weigh in on the matter into the fold. I encourage folks who talk like this to think carefully about claiming that they are like opinion-less infants.

There are only 2 ways to challenge a belief
As an atheist, in order to say that you don't believe in God and have that mean anything, you really have to have thought about it and decided that ascent to the claim would be intellectually wrong. You can fail to accept a claim by reaching one of two conclusions:

1. It's probably false. Believing that a claim is more likely to be false than true is a very good reason to not believe the claim. Arguing that a claim is false is known as making a de facto objection. The idea is that there is a fact of the matter regarding the claim and that fact is that it's false, or at least more likely to be false than true.

2. It's unjustified, or irrational. This is a different sort of objection that has nothing whatsoever to do with the veracity of the claim. Rather the objection is that, whether it's true or false, it's unjustified or irrational to believe. This is what's known as a de jure objection.

Here's an example. Say that I produce a lunch box and tell you that there is a hockey puck in it. You could rightly ask why I believe that. Did I look in it and see a puck? Did a reliable source tell me that there is a puck in it? Did I X-ray it and find a puck? If I answer in the negative to all of these sorts of queries, you would rightly question why I claimed that a puck is in the box in the first place. The objection here is that while there could be anything in the box including a puck, the reasons for believing that there is a puck in the box fail to justify that belief, ie. it's irrational.

So atheists have to decide what type of objection to theistic belief they have, and then they have a burden to defend that position. If an atheist thinks that the probability of God's existence is roughly 50/50, they can still advance the damning de jure objection that theistic belief is irrational, and I have absolutely no problem with that, even though most people (myself included) would probably call such a person an agnostic, rather than an atheist. But what atheists shouldn't do is believe in and make de facto objections to theism and then, when challenged, shift the burden of proof onto theists by retreating to a de jure objection, or even worse, to the preposterous position of claiming to have no belief whatsoever regarding the question of God's existence, like a newborn baby. To anybody looking upon this debate with fair eyes, these two moves look lame and shifty because they are.

The guys and gals who behave in the way I am spotlighting are very real and very strongly committed to their fallacious position. In it's defence, you'll hear them say things like:

"The burden of proof is always on the one making a positive claim."
Since the claim that God probably doesn't exist is a negative claim, they are relieved of their burden, or so they assert. But a little reflection reveals that this just isn't true. Imagine that I say that you should take an umbrella to work tomorrow because it's probably going to rain (a positive claim) and you say that you shouldn't because it probably isn't (a negative claim). Am I really the only one among us who has to have a reason for my particular belief? Would you automatically be rational despite having no reasons whatsoever for believing that it probably won't rain? That's nonsense. And besides, negative claims can always be rephrased as positive claims and it's absurd to think that merely rephrasing the same idea suddenly imposes a burden to support it. Here, watch:

Me: "It's not going to be a dry day tomorrow (negative claim), so you better bring your umbrella"

You: "Oh yes it is (positive claim). I'll leave my umbrella at home, thank-you."

By just rephrasing the claim, your negative claim is now a positive claim. Are we really supposed to believe that this rephrasing has suddenly switched the burden from me onto you?

So much for Modified Premise 1. You've got a claim (positive or negative)? You've got a burden.

"But You Can't Prove a Negative!"
One can prove a negative by finding a logical inconsistency in it. For example, I can prove that married bachelors don't exist because they can't. The logical problem of evil represents an attempt to prove that God doesn't exist because of the logical inconsistency posed by an omnipotent and morally perfect God in the face of evil and suffering in the world. Whether this logical argument is successful is another matter, but you get the idea.

One can also argue a negative evidentially. When evidence of a certain kind is expected given a particular claim, the absence of that evidence makes the claim less likely to be true. In other words, sometimes, absence of evidence really is evidence of absence.

For instance, if, whenever you bake a cake, the kitchen smells of baking, then it's reasonable to conclude that you probably didn't bake a cake whenever the kitchen lacks the scent of baking. There are several excellent evidential arguments against the existence of God (I explain a particularly powerful one here) and I encourage atheists to use them.

"No, you're wrong, and Russell's Teapot settles it"
In 1952, Bertrand Russell, a Nobel prize winner and influential philosopher of the 20th century, wrote a paper entitled “Is there a God?” wherein he outlined why he doesn’t believe. Included in the paper is this famous quote:
"Many orthodox people speak as though it were the business of skeptics to disprove received dogmas rather than of dogmatists to prove them. This is, of course, a mistake. If I were to suggest that between the Earth and Mars there is a china teapot revolving about the sun in an elliptical orbit, nobody would be able to disprove my assertion provided I were careful to add that the teapot is too small to be revealed even by our most powerful telescopes. But if I were to go on to say that, since my assertion cannot be disproved, it is intolerable presumption on the part of human reason to doubt it, I should rightly be thought to be talking nonsense. If, however, the existence of such a teapot were affirmed in ancient books, taught as the sacred truth every Sunday, and instilled into the minds of children at school, hesitation to believe in its existence would become a mark of eccentricity and entitle the doubter to the attentions of the psychiatrist in an enlightened age or of the Inquisitor in an earlier time."
Don't you just love that picture? That's the look I envision on his face when he reminds theists in that quote that it is not enough that theistic belief is widespread and that they therefore have a burden of proof. That's not in dispute. What is in dispute is whether the notion that theism is probably false also has a burden, and nowhere does Russell suggest that it does not.

Russell's teapot is meant to prevent theists from employing the fallacy of "shifting the burden of proof" onto atheists, and that is all. Ironically, atheists who think that God probably doesn't exist and then claim that the burden is entirely on theists to argue that he does are as guilty of shifting the burden of proof as the theists that Russell was scolding. A case of the teapot being as black as the kettle, perhaps?

"But ... The Legal Burden of Proof!"
It is true that in criminal cases, the one charging another with breaking the law (ie. the state) has the burden of proof. The defendant has no burden to prove that she is innocent because she is presumed to be (which doesn't mean that she is, of course). At a minimum, all that the defence must do is show that the prosecution's evidence is weak and therefore raise a reasonable doubt about the accused's guilt. Things are this way to prevent the state from abusing its power. Can you imagine if the state could accuse somebody of a crime and punish them unless they could prove themselves innocent? No person would be free of the threat of that kind of tyranny.

It is noteworthy that the verdict in a criminal case is either 'guilty' or 'not guilty'. Courts never reach a verdict of 'innocent' beyond a reasonable doubt and it would be disingenious for the defence to claim that the defendant was innocent if all they argued was that she was not guilty. Why? Because they would not have met their burden for *that* claim. OJ Simpson was found not guilty, but that clearly didn't mean that he was innocent. Similarly, atheists who believe and claim that theism is probably false are disingenuous if all they do is argue that theistic belief is unjustified or that they lack belief the way a baby does. Why? Because they aren't meeting their burden for the claim that theism is probably false, which is what they really believe.

Outside a criminal court, in discussions about the existence of God, or who would make a good President, or whether the minimum wage should be raised, etc. the burden of proof that matters is the "Philosophical Burden of Proof" and it applies equally to both sides of a claim for we don't presume that a claim is true or false. Accordingly, both sides can be guilty of shifting their burden fallaciously when they try to avoid it.

So there is a reason that criminal courts have an asymmetric burden of proof, but they nevertheless do not reach conclusions beyond what is successfully argued for. If atheists want to avoid their burden of arguing that theism is probably false, they too should not reach or hold conclusions beyond what they are prepared to argue for.

"Extraordinary Claims Require Extraordinary Evidence"
This quote from Carl Sagan is true, to be sure,  but it's also a word game that atheists who want to avoid their burden of proof like to use and it's really quite easy for the theist to dismiss. All the theist must do is ask what makes God's existence an 'extraordinary' claim.

The answer can’t simply be that the evidence and arguments in support of God's existence are insufficient. That only permits one to say that belief in God is unjustified, and while the atheists I'm addressing in this post do think that belief in God's existence is unjustified, they also believe much more than that. They also believe that God's existence is unlikely, and that's a claim that they have to be prepared to back up. You see, saying that a claim is extraordinary is just a dramatic way of saying that it's probably false. The low probability of it being true is what makes the claim that it nevertheless is true, extraordinary. Switching in the word "extraordinary" for "unlikely" doesn't magically make the burden of showing God's existence to be unlikely disappear. And so, when the atheist explains why they think that God's existence is "extraordinary", they will then be addressing the burden of that claim.

"I Don't Have a Burden Because I'm Not Trying to Change Anybody's Mind"
There are 2 responses to this. The first is that if you are involved in a discussion about who has the burden of proof, you are necessarily talking about situations where at least two people disagree and are trying to convince the other of their error. The second is that you have a burden to yourself, in order for your beliefs to be rational, to make sure that they are justified.

"I'm Not Making a Claim to Knowledge"
Here's some important news for anybody tempted to use this canard: if your reasoning is evidence-based, you are always dealing with probabilistic beliefs. Whether you know it or not, when you update your beliefs based on new evidence, you're employing Bayesian reasoning, and the result of Bayesian reasoning is always probabilistic. The difference between a hunch, a belief, and knowledge is just a matter of the probability you assign to the truth of the claim. Your evidence-based reasoning doesn't suddenly acquire a burden of proof when the probability you assign to the truth of a claim reaches whatever threshold you have for calling it knowledge. If you have a hunch, you have a burden. If you have a weak belief, you have a burden. If you have a strong belief, you have a burden. If you think that you "know" something, you have a burden. These burdens are not all equally heavy, to be sure, but they are all very real and shouldn't ever be ignored.

"If I Have To Disprove God, then I Have to Disprove Everything"
This is an obvious non-sequitur. It just doesn't follow from the fact that you must have reasons for your beliefs that you're obliged to anticipate every potential claim and disprove it. You just have to have reasons to support what you've come to believe.

"Prove that unicorns that ride rainbows and fart glitter don't exist"
This was an actual response that I received when I merely suggested that atheists who think that theism is probably false carry a burden of proof. This challenge seems to be a combination of "You can't prove a negative" and "If I have to disprove God, then I have to disprove everything" rolled into one. I suspect that the reasoning was that if one isn't capable of meeting this burden, then it's completely unfair to tell any atheists that they have a burden, too. Here was my response:
"Unicorns are large horse-like animals. Humans have pretty much searched all of the possible habitats for large horse-like animals and reliable evidence of the existence of unicorns, including unicorn remains, unaltered photographs, caged unicorns, etc. have never been produced. Since we could very reasonably expect to find such evidence of the existence of unicorns if they actually existed, the fact that we have not is very powerful evidence against the existence of unicorns. Since we have very powerful evidence against the existence of unicorns, we also have very powerful evidence against the existence of unicorns that ride rainbows and fart glitter. The existence of those specific unicorns, with no evidence in the tree of life of any other animals with such capabilities nor any reason why those capabilities would've evolved, is astronomically unlikely. Furthermore, the notion of  a material being riding a rainbow seems incoherent. The extremely low probability of the existence of such unicorns constitutes what I would consider to be proof that they don't exist. As an epistemic fallibilist, I always leave room for the possibility of being wrong, but the matter has been established to my satisfaction: unicorns that ride rainbows and fart glitter don't exist."
There are some folks who claim to be agnostic about God the same way that they are agnostic about unicorns. I hope it's clear that we don't have to be agnostic about unicorns.

A Way Forward
Because the term 'atheist' is vague and fails to identify whether one has de jure or de facto objections to theism of varying strengths, I propose that people just state what they believe regarding the particular God(s) in question, and how strongly they believe it. In his book, The God Delusion, Richard Dawkins rightfully acknowledged that our beliefs are held with varying degrees of confidence and provided a seven-point scale of belief (more on that here). Notice that the only real "default position", which isn't a position at all, but rather, is the psychological state that exists when someone hasn't yet formulated a belief, isn't even on the scale. Once one forms an opinion about the existence of particular God(s), then atheists and theists alike should figure out where on the scale they sit, and then defend that position. An atheist who's only prepared to claim that theism is unjustified should probably identify as a 4 on that scale. Such atheists really don't have a burden to prove that theism is more likely false than true because they're what most people would call agnostic and are therefore making no such claim. If an atheist identifies between 4.1 and 7, then they have a burden to explain why they think that theism is more likely to be false than true, just as a theist who identifies as a 1-3.9 has the opposite burden. There is no special burden of proof that one side has that the other doesn't, and perpetuating this lie creates a toxic situation where both sides try to shift their burden onto the other. I never want to see my fellow atheists trying to shift their burden onto theists by advancing the lie that they're opinion-less infants, or that their only burden is to reject the evidence and arguments in favour of theism. If you think that God's existence is more likely false than true, you obviously have to do all of that plus more. My request is one that no good atheist should ever resist, for all I'm asking is that you defend what you really believe.

If you want to become familiar with arguments, including evidential arguments, against theism, I suggest following Justin Schieber at Real Atheology, and on Twitter and Facebook.