Should We Poo Poo Miralax

1
Should We Poo Poo Miralax?

• Journal Club 10/16/06
• Cynthia DAlessandri M.D.
• Department of Pediatrics
• Yale University
• School of Medicine

2
Clinical Case

• 6 y.o. male with 2 month history of intermittent
  constipation, who presents with 1 week history of
  fecal incontinence.
• 1-2 BMs weekly
• Previously continent
• Not on any medications
• Exam reveals large hard stool in vault

3
Clinical Question

• In school age children with fecal
• incontinence secondary to
• constipation, is Miralax as effective
• as Milk of Magnesia (MOM) for
• treating constipation?

4
Search Key Words

• Polyethylene Glycol, Milk of Magnesia,
  constipation, fecal incontinence
• Limits EBM, English, all children (1-18 yrs)
• Article Loening-Baucke V. Pashankar DS. A
  randomized, prospective, comparison study of
  polyethylene glycol 3350 without electrolytes and
  milk of magnesia for children with constipation
  and fecal incontinence. Journal Article.
  Randomized Controlled Trial Pediatrics.
  118(2)528-35, 2006 Aug.

5
Methods

• From Aug 2001 to Sept 2004 children with fecal
  incontinence and constipation
• 79 children assigned randomly to either Miralax
  or Milk of Magnesia
• Inclusion criteria
• 4 18 years old
• Functional constipation 8 weeks
• At least 2 other criteria 1 episode
  of fecal incont wkly, lg stool in rectum, stools
  which obstruct toilet, witholding behavior

6
Methods

• Follow up at 1, 3, 6, 12 months
• Phone call at 9 months
• Labs at 3, 6, 12 months
• Only 2 authors recruited all the children

7
Is My Study Valid?

• Randomization, Concealed randomization - YES All
  patients were randomized by drawing a sealed
  envelope
• Blinded - NO This study was not blinded due to
  difference in the administration of the 2
  therapies studied
• Complete follow up- ?? 4 patients (2 from each
  group) were lost to follow up, giving knowledge
  of the status of 95 of patients.
• All patients lost to follow up or discontinued
  from study were assumed to be not improved- this
  can negatively affect outcomes

8
Is My Study Valid?
Loening-Baucke, V. et al. Pediatrics
2006118528-535
FIGURE 1 Trial profile
9
Is My Study Valid?

• Patients analyzed in original groups- YES all
  patients were analyzed in their groups on
  intention to treat basis
• Similarity of groups- YES there was no
  significant statistical difference between the
  two groups
• This study is VALID depending on the clinical
  situation/outcome of interest

10
Results

• Compare MOM with PEG in terms of improvement and
  recovery at 12 months
• RRR the proportional reduction in rates of bad
  outcomes between experimental and control
  participants in a trial

11
Results

• Compare MOM with PEG in terms of improvement and
  recovery at 12 months
• ARR the absolute difference in rates of bad
  outcomes between experimental and control
  participants in a trial

12
Results

• Compare MOM with PEG in terms of improvement and
  recovery at 12 months
• NNT the number of patients who need to be
  treated to achieve one additional favorable
  outcome

13
Results

• Compare MOM with PEG in terms of improvement and
  recovery at 12 months
• How precise was the estimation of effect?

14
Results

• How precise was the estimation of effect?
• 95 Confidence interval on ARR
• These both cross zero NO DIFFERENCE
• 95 Confidence interval on NNT
• Unable to apply since the results are negative

15
Results

• Unfortunately the results are invalid based on
  the CI for NNT
• The risk reduction was also proven to be null- no
  statistically significant difference between the
  2 medications

16
Results

• The biggest flaw in results due to incongruent
  loss in pts from MOM group compared with the PEG
  group
• The loss of pts in MOM group made the study
  invalid due to loss of power (N)

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HUH????

• GOAL
• to show that one treatment is better than
  another
• or
• to prove that one treatment is indistinguishable
  from another
• You are not trying to prove that one treatment
  makes a statistically significant difference in
  the outcome
• You are trying to prove that two treatments are
  essentially equivalent, that any difference is of
  no practical consequence
•  

18
Assessment of Utility

• Can I use this to guide me clinically?
• No the study itself is invalid
• PEG more expensive than MOM however our
  population has state insurance which will cover
  all of PEG and possibly not OTC MOM

19
Assessment of Utility

• Treatment benefits far outweigh the risks
• Only 1 child out of 39 experienced allergic
  reaction and this reaction was not life
  threatening
• Incidence of allergy unknown- very rare
• All labs were essentially benign

20
Assessment of Utility

• Many clinically important outcomes were
  considered
• Improvement and recovery from symptoms were
  monitored and analyzed
• Secondary outcomes were also measured including
  the patients acceptance and compliance, which is
  key in our population

21
Break It Down C-Dawg

• Very valid study methods
• Lack of Importance
• Very invalid study results due to higher drop out
  rate in MOM group results skewed
• 95 compliance in PEG vs. 65 in MOM
• Did MOM get gypped?

22
References

• Yale Pediatric Residency ProgramEvidence-Based
  Medicine (EBM) Journal Club Website
• Special thanks to Dr. Ada Fenick