31 August 2012

Pathfinder vs Researchers: Disagreement Over Use of Misoprostol for Postpartum Hemmorhage

When women experience postpartum hemmorhage (PPH) the drug Oxytocin is the first line choice to reduce or stop bleeding. It is an important drug because PPH was responsible for 1/4 of the 358,000 maternal deaths that occurred in 2008.
In resourced strapped areas, a new oral drug called Misoprostol provides help to mothers who experience PPH. While Oxytocin is the preferred choice, there are many cases where women give birth outside of a hospital or the hospital itself is unable to carry the drug.

Misoprostol is so important that the WHO Expert Committee on the Selection and Use of Essential Medicines added it to the Essential Medicines list for use when Oxytocin is not available. They wrote in 2010,
For PPH prevention, WHO recommends that “in the absence of active management of the third stage of labour, a uterotonic drug (oxytocin or misoprostol) should be offered by a health worker trained in its use for prevention of PPH. For misoprostol, this recommendation places a high value on the potential benefits  of avoiding PPH and ease of administration of an oral drug in settings where other care is not available, but notes there is only one study. The only trial relevant to this recommendation used 600 μg of misoprostol.6 The efficacy of lower doses has not been evaluated. There is still uncertainty about the lowest effective dose and optimal route of administration.”
A recent paper raises some questions about the evidence that supports the use of Misoprostol. The abstract says:
This article describes and critically appraises clinical trials assessing misoprostol effectiveness in preventing primary postpartum haemorrhage (PPH) in home and community settings in low- and middle-income countries. Of 172 identified studies of misoprostol use in labour only six fulfilled the inclusion criteria. All trials used 600μg misoprostol in the intervention arm; three assessed misoprostol alongside components of active management of the third-stage labour (AMTSL), two used expectant management of labour and one allowed birth attendants to choose management practice. The three AMTSL studies showed no significant differences in PPH incidence or referral to higher centres and only one study showed significant decrease in severe PPH using misoprostol. One expectant management study and the choice of management by birth attendants study found significant decreases in PPH incidence with misoprostol. All studies showed significantly increased risk of shivering with misoprostol. Studies were biased by use of alternative uterotonics in the control arm, confounding management practices, and subjective assessment and, with one exception, exclusion of high-risk women. PPH incidence fell in both the control and intervention groups in both the landmark papers that informed the World Health Organization (WHO) decision to admit misoprostol to the Essential Medicines List. This suggests factors other than misoprostol use are crucial. Current evidence does not support misoprostol use in home and community settings in low- and middle-income countries for PPH prevention. WHO should rethink its recent decision to include misoprostol on the Essential Medicines List.
Pathfinder International disagrees with the assessment by the study's authors. Pathfinder questions the methodology of the authors of the study by saying that little information is provided as to how they analyzed the various studies. They outline other points of disagreement writing,
[T]he paper criticizes one study that used visual estimation of blood loss (VEBL), suggesting that blood loss
could have been underestimated. This is a valid critique of VEBL, as it is known to underestimate blood loss. However, there is no reason to suspect that VEBL was applied differently in the two study groups, so under-estimation is equally likely in both the intervention and control groups and would not differentially affect the findings. In other words, there is no reason to think that the differences the original study reported are the result of VEBL.

Finally, the authors criticize a number of the studies that they reviewed for having had extensive exclusion criteria. We, however, believe that the criteria used in the original studies are completely reasonable. For example, it would not be possible to include in a study people who refuse to participate or, in this case, women who did not have access to the intervention or control because either the drugs or the person to administer them was not available at the delivery. No study can include potential participants who do not have access to the study intervention.
Pathfinder recommends that no changes be made to current guidelines. They admit that the use of Misoprostol is not an end, but a way to address present health constraints in resource-deprived settings.