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Centre for Evidence-
Based Medicine

Completed Systematic Reviews Worksheet for Evidence-Based Neonatal Medicine

Citation

Fowlie PW. Prophylactic intravenous indomethacin in very low birth weight infants (Cochrane Review). In: The Cochrane Library, 1997. Oxford: Update Software.

Are the results of this systematic review (systematic review) of therapy valid?

  1. Is it a systematic review of randomised trials of the treatment you're interested in?
    Yes.
  2. Does it include a methods section that describes finding and including all the relevant trials?
    Yes.
  3. Does it include a methods section that describes assessing their individual validity?
    Yes.
  4. Were the results consistent from study to study?
    All trials suggest that prophylactic indomethacin is associated with short-term benefits, namely reduction of Patent Ductus Arteriosus (PDA) and severe Intraventricular Hemorrhage (IVH grade 3 and 4). Whether or not this results in improved survival without disability has not been sufficiently evaluated.

Are the valid results of this systematic review important?

Translating odds ratios to NNTs. The numbers in the body of the table are the NNTs for the corresponding odds ratios at that particular patient's expected event rate (PEER).
Odds Ratios
0.9 0.85 0.8 0.75 0.7 0.65 0.6 0.55 0.5
Patient's Expected Event Rate (PEER) 0.05 2091 139 104 83 69 59 52 46 412
0.10 110 73 54 43 36 31 27 24 21
0.20 61 40 30 24 20 17 14 13 11
0.30 46 30 22 18 14 12 10 9 8
0.40 40 26 19 15 12 10 9 8 7
0.503 38 25 18 14 11 9 8 7 6
0.70 44 28 20 16 13 10 9 7 6
0.90 1014 64 46 34 27 22 18 15 125
  1. The relative risk reduction (RRR) here is 10%
  2. The RRR here is 49%
  3. For any OR, NNT is lowest when PEER = .50
  4. The RRR here is 1%
  5. The RRR here is 9%

For all IVH:
Control Event Rate (CER) = 221/614 = 0.3599
Experimental Event Rate (EER) = 161/598 = 0.2692
OR = 0.61
NNT is approximately 10.

For IVH Grade 3 and 4:
Control Event Rate (CER) = 80/599 = 0.1336
Experimental Event Rate (EER) = 46/577 = 0.0797
OR= 0.55
NNT is approximately 18

For symptomatic PDA:
Control Event Rate (CER) = 135/410 = 0.3293
Experimental Event Rate (EER) = 46/403 = 0.1141
OR = 0.29
NNT is approximately 5.

Can you apply this valid, important evidence from a systematic review in caring for your patient?

Do these results apply to your patient?

  1. Is your patient so different from those in the systematic review that its results can't help you?
    No

How great would the potential benefit of therapy actually be for your individual patient?

  1. Method I:
    In the table on page 1, find the intersection of the closest odds ratio from the overview and the CER that is closest to your patient's expected event rate if they received the control treatment (PEER):
    See above approximate NNTs.
  2. Method II:
    To calculate the NNT for any OR and PEER:
    NNT = (1-(PEERx(1-OR))/((1-PEER)xPEERx(1-OR))

Are your patient's values and preferences satisfied by the regimen and its consequences?

  1. Do your patient and you have a clear assessment of their values and preferences?
    Yes.
  2. Are they met by this regimen and its consequences?
    Yes.

Should you believe apparent qualitative differences in the efficacy of therapy in some subgroups of patients?

Not applicable; there have been no subgroup analyses.

Additional Notes

Despite the evidence of short-term benefits, indomethacin prophylaxis is not widely used in many countries, due to concerns about drug safety (e.g. the risk of necrotizing enterocolitis and gastro-intestinal perforations) and the lack of convincing data on long-term outcomes after indomethacin prophylaxis in this high-risk population.

Therefore, an international placebo-controlled trial was launched in 1996, to determine whether the prophylactic administration of low-dose indomethacin to infants weighing 500-999 grams at birth improves survival without neurosensory impairment to a corrected age of 18 months. This trial is funded by the Medical Research Council of Canada, and co-sponsored by the National Institute of Child Health and Human Development. Twelve-hundred and two infants have been enrolled between 1996 and 1998 in Canada, the US, Australia, New Zealand and Hong Kong. Follow-up will be completed early in the year 2000. For further information, please contact Barbara Schmidt.

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