There is a great deal of speculation concerning the endof the world in December 2012, coinciding with theend of the Mesoamerican Long Count calendar (the

“Maya calendar”). Such an event would undoubtedly affectpopulation survival and, thus, survival outcomes in clinicaltrials. Here, we discuss how the outcomes of clinical trialsmay be affected by the extinction of all mankind and recom-mend appropriate changes to their conduct. In addition, weuse computer modelling to show the effect of the apocalypseon a sample clinical trial.

Mostly true backgroundWith the imminent completion of the Maya calendar, many“experts” suspect the end of the world will occur on Dec. 21,2012.1,2 This impending apocalypse highlights the need torapidly resolve many major issues in research methods. Beingbased in an academic institution and fully respectful and com-pliant with all issues concerning Good Clinical Practice guide-lines, we have been told that a tenet of human research is thatall clinical trials must report and disseminate statistical resultsin a timely manner for the bene!t of patients and the wider sci-enti!c community.3 Given the anticipated effect of the apoca-lypse, hence known as Mayan Doomsday (MaD), on survivaloutcome measures, research methods must be adjusted for theexpedited analysis of all clinical research currently in pro gress.We recognize that reviewers, editors and even readers of thisarticle may !nd the premise of our commentary rather fantasti-cal. However, we defend the importance of our opinion byquoting the great medical forefather Louis Pasteur:

Where observation is concerned, fortune favours only the preparedmind.

Stuff we didUsing computer modelling (described elsewhere ad nau-seum, ad in!nitum), we have generated Kaplan–Meiercurves for the overall population to compare normal lifeexpectancy from standard actuary tables (control group) withpopulation survival after MaD (obliteration group). Thesemethods were then hypothetically applied to a standard clini-cal trial design.

Stuff we found outThe difference in survival between the control and oblitera-tion groups is shown in Figure 1. For the control group, deathoccurs at a predictable and fairly uniform rate. However,MaD leads to a statistically signi!cant, and clinically rele-vant, difference in survival between the control and oblitera-tion groups (we’re pretty sure that, were it calculated, pwould de!nitely be something really signi!cant, and cer-tainly less than 0.05). Oddly, despite censoring for majorknown sources of bias (e.g., astronauts currently aboard theinternational space station, as well as zombies, the undead,the Grateful Dead, Dungeons and Dragons players, men whohave read Fifty Shades of Grey and other similar beings likely

Unsubstantiated Theory

The Mayan Doomsday’s effect on survival outcomesin clinical trials

Paul Wheatley-Price MBChB MD, Brian Hutton MSc PhD, Mark Clemons MBBS MD

© 2012 Canadian Medical Association or its licensors CMAJ, December 11, 2012, 184(18) 2021

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to be unaffected by the apocalypse), the obliteration groupdoes not fall to 0. We have dubbed this slow rise in the oblit-eration curve the “zombie repopulation.”

Additional modelling was done to assess the effects ofMaD on a sample clinical trial comparing the ef!cacy of 2 !c-tional, although completely plausible, drugs: Toxico and Hor-ribilum. As can be seen in Figure 2A, compared with patientsreceiving Horribilum, those receiving Toxico had longermedian overall survival. When the effect of MaD is added tothe model (Figure 2B), no difference in survival can be seenbetween the 2 drugs. Furthermore, any adverse events wouldnot be able to be recorded owing to “the mother of all adverseevents,” and any statistical signi!cance between study armswould be lost.

Chit chatIf we have been thinking clearly, then it is apparent that theend of the world will have catastrophic effects on statisticalanalyses of survival outcomes. We therefore recommend thatall clinical trials should stop immediately, as MaD will negateall potential trial results.

However, are trials such as those between our two !ctionaldrugs entirely redundant in the event of MaD? It is possiblethat some useful scienti!c data could be salvaged. Late effectsof these drugs could potentially be studied during the zombierepopulation, assuming that the original consent forms wouldstill be considered valid (surely folks on the ethics board willhave survived). Unfortunately, this work may be pragmaticallychallenging, as we suspect that most members of researchteams may themselves be obliterated. (Due to sheer misfor-tune, all of the authors of this paper missed the biannual“Defense Against Zombies” seminar held in our institution.)

The possibility of a zombie repopulation is an unexpected!nding in the event of MaD. Before MaD, the walking deadwere most commonly relegated to young adult novels andcable specialty channels and were not observable with stan-dard scienti!c techniques. Their putative existence does, how-

ever, bring a new dimension to the recent opening of multiplesurvivorship centres — although, if the new world populationis predominantly immortal, we have concerns for the capacityof such programs. However, we would never allow such prac-tical considerations to impair the scienti!c process.

ConclusionMaD is bad.

References1. 2012 phenomenon. Wikipedia. Available: http://en.wikipedia.org/wiki/2012_phe-

nomenon (accessed 2012 Sept. 18). 2. MacDonald GJ. Does Maya calendar predict 2012 apocalypse? McLean (VA):

USA Today; 2007. Available: http://usatoday30.usatoday.com/tech/science/2007-03-27-maya-2012_n.htm (accessed 2012 Sept. 18).

3. Vijayananthan A, Nawawi O. The importance of good clinical practice guidelinesand its role in clinical trials. Biomed Imaging Interv J 2008;4:e5.

Correspondence to: Paul Wheatley-Price, pwheatleyprice@toh.on.ca

Af!liations: Paul Wheatley-Price and Mark Clemons are from the Departmentof Medicine, Division of Medical Oncology. Brian Hutton is with the OttawaHealth Research Institute Methods Centre, University of Ottawa, Ottawa, Ont.

CMAJ 2012. DOI:10.1503/cmaj.121616

2022 CMAJ, December 11, 2012, 184(18)

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Figure 2: Kaplan–Meier curves comparing overall survival amongpatients receiving Toxico or Horribilum. (A) Results without theimpact of Mayan doomsay. (B) Results with the impact of Mayandoomsday.

Zombie repopulation

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Figure 1: Survival curves for the overall population with andwithout the occurrence of Mayan doomsday. MaD = Mayandoomsday. Note heretofore unforeseen postapocalyptic zombierepopulation.