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Tuesday, May 30, 2017

Clustering of Drugs by Side Effect Profile

Others (here, herehere + others) have clustered medications based on side effect profiles. Everyone has done it a little differently.

In this post, I perform a similar type of clustering using slightly different methods (details forthcoming). I'm not providing m̶u̶c̶h̶ any of the methodological details in this post, but I just wanted to show a pretty plot with nice clusters.

Drugs were clustered using t-SNE (here and here), which is a method that is remarkably good at taking high-dimensional data (in this case, thousands of different side effects) and clustering it into 2-dimensions while maintaining much of the "nearest neighbor" information that was present at high dimensions.

You can see the 2-D "cluster plot" (after t-SNE transformation) below.

  • Hover over the data points to see drug names.
  • I colored the data points by running k-means on the 2-D data (very quick and dirty and probably not the best approach).
  • Still, you can see pretty good functional clustering. For example: 
    • the dark green points on the left edge of the plot are almost all related to cholesterol and lipid pharmacotherapy. If you zoom in, you will also find daptomycin (an anti-bacterial), but it clusters there b/c it is associated with reports of myopathy and rhabdomyolysis (adverse events that are somewhat characteristic of the "statins").
    • red and blue points on the left edge are primarily involved w/ Type 2 diabetes.

Friday, March 17, 2017

Trump submitting adverse event reports?

Found this "classic" adverse event report submitted to the FDA in 1994. 76 year old male patient taking Sinemet and Xanax with a report of the following issues:

  • asthenia
  • coordination abnormal
  • dysphagia
  • med error

The kicker is in the comments section: 'Pharmacist "jokingly" told patient to take the medication with Vaseline, [which] the patient did.'

  • First, I'm not sure why jokingly is in quotes. Was the reporter quoting the pharmacist, in which case the quotation marks emphasize a literal and sincere description of the communication between pharmacist and patient? Or are the quotation marks meant in the ironic-2017-Sean-Spicer-fake-news sense, in which case the pharmacist comes across as malevolent? Tough call.

  • Second, the report labels the Sinemet as the suspect medication! I'm going to go out on a limb and speculate that the Vaseline itself was causing the dysphagia, but don't quote me on that.

Saturday, February 25, 2017

I'm trying to make a dictionary of drugs named in FAERS and their active ingredient(s).

Let's see how many ways we can abbreviate, misspell name a drug that contains paracetamol/acetaminophen:
  1. acamol
  2. aceminophen
  3. acetam
  4. acetametamin
  5. acetamilnophen
  6. acetamin
  7. acetaminaphine
  8. acetamino
  9. acetaminofen
  10. acetaminohen
  11. acetaminop
  12. acetaminopehn
  13. acetaminopen
  14. acetaminoph
  15. acetaminopham
  16. acetaminophe
  17. acetaminophen
  18. acetaminophen0
  19. acetaminophin
  20. acetaminophn
  21. acetaminphen
  22. acetamiophen
  23. acetamonophen
  24. aceteminophen
  25. acetminophen
  26. acetomeniphen
  27. acetominopehn
  28. acetominophen
  29. actigrip
  30. actyaminphen
  31. adetaminophen
  32. algisedal
  33. algotropyl
  34. alpiny
  35. alvedon
  36. alvedone
  37. amidrine
  38. anhiba
  39. antalvic
  40. apap
  41. aplexil
  42. aracetamol
  43. atasol
  44. butal cf acetamn
  45. calonal
  46. calpol
  47. car panadol
  48. claradol
  49. cocodamol
  50. codamol
  51. codoliprane
  52. coltalin
  53. combiflam
  54. comtrex
  55. dafagan
  56. dafalgan
  57. daflagan
  58. defalgan
  59. depalgos
  60. depon
  61. dexamol
  62. dextr neo citran
  63. di antalvic
  64. dolipran
  65. doliprane
  66. dristan
  67. efferalgan
  68. endocet
  69. esgic
  70. excedrin
  71. excedrin migraine
  72. exedrin
  73. exedrin asa
  74. fervex
  75. feverall
  76. fioricet
  77. frenadol
  78. grippostad
  79. hycet
  80. hydroc/apap
  81. hydroco apap
  82. hydroco/acetaminophen
  83. hydroco/apap
  84. hydrocod/acetam
  85. hydroodone/apap
  86. ixprim
  87. kolibri
  88. lamaline
  89. liq tyelnol
  90. loratab
  91. lorcet
  92. lortab
  93. mapap
  94. maxidone
  95. maxiumum midol pms
  96. midol
  97. midol pms
  98. midrin
  99. migrazone
  100. miradol
  101. mission supac
  102. neo citran
  103. neocibalena
  104. norco
  105. ofirmev
  106. osteo panadol
  107. oxy/apap
  108. oxycod/apap
  109. pactiv
  110. panadeine
  111. panadol
  112. panodil
  113. parace
  114. paracematol
  115. paracemtamol
  116. paracet
  117. paraceta
  118. paracetam
  119. paracetamil
  120. paracetamo
  121. paracetamol
  122. paracetamol0
  123. paracetamolo
  124. paracetmol
  125. paracetmol aporex
  126. paracetramol
  127. paractol
  128. parad
  129. paralgin
  130. paralyoc
  131. paramol
  132. percocet
  133. perfalan
  134. perfalgan
  135. pro dafagan
  136. prontalgine
  137. proparacetamol
  138. pyrinazin
  139. roxicet
  140. saridon
  141. sinex
  142. sinutab
  143. tachidol
  144. tachipirina
  145. traiminic
  146. tramcet
  147. trimanic
  148. tyelnol
  149. tyenol
  150. tylenol
  151. tylenolpm
  152. tylonal
  153. ultracet
  154. ultraset
  155. xartemis
  156. xolox
  157. zapain
  158. zydone

                                                                                                                                                                                                                                                                                                                          Thursday, January 19, 2017

                                                                                                                                                                                                                                                                                                                          Friday, January 13, 2017

                                                                                                                                                                                                                                                                                                                          FDA MAUDE, Patient Outcomes and "8."

                                                                                                                                                                                                                                                                                                                          The FDA's MAUDE database contains reports on malfunction of medical devices. You can run more comprehensive searches here.

                                                                                                                                                                                                                                                                                                                          There's a lot of information buried in the MAUDE database, including the outcomes of patients who were on the receiving end of a malfunctioning device.

                                                                                                                                                                                                                                                                                                                          Specifically, the MAUDE database uses a 1-letter code to list the following possible outcomes:
                                                                                                                                                                                                                                                                                                                          • Congenital Anomaly (C)
                                                                                                                                                                                                                                                                                                                          • Death (D)
                                                                                                                                                                                                                                                                                                                          • Disability (S)
                                                                                                                                                                                                                                                                                                                          • Hospitalization (H)
                                                                                                                                                                                                                                                                                                                          • Life Threatening (L)
                                                                                                                                                                                                                                                                                                                          • Other (O)
                                                                                                                                                                                                                                                                                                                          • Required Intervention (R)
                                                                                                                                                                                                                                                                                                                          • plus a few others that are not particularly interesting.
                                                                                                                                                                                                                                                                                                                          Lately, the FDA has stopped listing patient outcomes and have replaced them with the following cryptic message: 8.  That's right, the digit 8 and a period. I have no idea what that means, but there has been no patient outcome information (other than "8.") in the MAUDE database for ALL of 2016.

                                                                                                                                                                                                                                                                                                                          Let's take a look at the rise of "8." (see blue line below).  If we go back to 2012 and 2013, we can see that only 1 - 5% of MAUDE reports had an outcome of "8."

                                                                                                                                                                                                                                                                                                                          Things start to change in the spring of 2015, when "8." begins an exponential march upward.

                                                                                                                                                                                                                                                                                                                          By October 2015, 100% of the MAUDE reports show an outcome of "8." and it hasn't relinquished its stranglehold since.

                                                                                                                                                                                                                                                                                                                          I have no idea what "8." means. 

                                                                                                                                                                                                                                                                                                                          • Is it a database error? 
                                                                                                                                                                                                                                                                                                                          • Does it mean that the FDA has stopped releasing this information?
                                                                                                                                                                                                                                                                                                                          • Something else entirely?

                                                                                                                                                                                                                                                                                                                          If anyone knows what "8." means, please let me know!!!

                                                                                                                                                                                                                                                                                                                          Here's some additional weirdness.

                                                                                                                                                                                                                                                                                                                          The graph shown above only goes back to late 2012.
                                                                                                                                                                                                                                                                                                                          You can go all the way back to 1991 and plot MAUDE outcome data.
                                                                                                                                                                                                                                                                                                                          What you see are periodic spikes of "8." (see blue line in chart below).

                                                                                                                                                                                                                                                                                                                          Again, I have no idea why "8." would take up 30+% of the patient outcomes in September of 2004, but it's there.

                                                                                                                                                                                                                                                                                                                          We need more of this.

                                                                                                                                                                                                                                                                                                                          And then there's MAUDE

                                                                                                                                                                                                                                                                                                                          FDAble also provides clients with adverse event and malfunction information for medical devices using the FDA's MAUDE database. MAUDE is an acronym for Manufacturer and User Facility Device Experience Database. I think we can all agree that this is a horrible name, unless you are a fan of Bea Arthur

                                                                                                                                                                                                                                                                                                                          The MAUDE database is weird in so many ways (more about that in a future post), but one of its remarkably nice features is that it provides a free-form narrative describing the problem associated with each report. In contrast to MAUDE, the FDA does not provide the narratives for FAERS data (unless you file a FOIA request and are willing to wait about 1 month).

                                                                                                                                                                                                                                                                                                                          From the looks of it, the FDA currently receives about 80-90 thousand MAUDE reports per month (which is roughly the same magnitude as the number of FAERS reports received per month as well). You can also see that MAUDE recently celebrated its 300th month anniversary (starting in December of 1991).

                                                                                                                                                                                                                                                                                                                          The FDA started including manufacturer reports in August of 1996, which explains the giant leap in the # of reports at that time.