Michael C. Klein Centre Community Child Health Research

1. Edmonton May 7th 2011 Throwing the Mother Out with the Bathwater—Misuse of randomized controlled trials Michael C. Klein Centre Community Child Health Research BC Research Institute for Children’s and Women’s Health Emeritus Professor of Family Practice and Pediatrics University of British Columbia

2. Variation surfaces Vancouver CQI 1993

3. Epidural Cxion

4. A natural experiment at nearby community hospital • In early 1990s Community Hospital had Cxion rate of about 8%, while Women’s about 20% • Created matched cohort of healthy women • Odds of having a Cxion at the tertiary care centre vs community 3.4 (CI 2.1—5.4) • Why? • More advanced cervical dilation on arrival • Use of epidural analgesia—largest effect: Epidural rate of 15.4% community, 67.2% tertiary Janssen P, Klein MC. Differences in Institutional Cesarean Delivery Rates: The role of pain management. J Fam Pract 2001; 50(3):217-223

5. A natural experiment at nearby community hospital • Differences between the hospitals: • Increased ambulation at the community (12% vs 5%) • Fewer numbers of caregivers for each woman at community • More oxytocin augmentation at community (32.3 vs 24.9%) • Less offering of epidural at community (qualitative) 16.7% vs 42.3% • Strong Head of OB at community who worked collaboratively with strong nursing and FP leadership, and together developed a coherent philosophy of care

6. A natural experiment at nearby community hospital • But when controlled for epidural, the Cxion rate at the two hospital was the same, about 12% • In other words, women with an epidural in each facility had a similarly high Cxion rate and women not receiving an epidural had a similarly low Cxion rate • Only real difference was: community hospital used epidural less often, and in so doing had a low Cxion rate • When Head of OB retired and nursing leadership also changed, the epidural and Cxion rate at the community hospital rapidly reached usual levels for BC • Nevertheless can’t say it is causal—only an hypothesis Janssen P, Klein MC. Differences in Institutional Cesarean Delivery Rates: The role of pain management. J Fam Pract 2001; 50(3):217-223

7. Meanwhile Departmental CQI evolved into research • We studied natural variation in relation to physician epidural rates • Maternal outcomes • Newborn outcomes • The physician rather than the woman as the unit of analysis

8. Nulliparous Maternal Outcomes by Epidural Cohorts

9. Epidural study

10. Were the physicians who were in each epidural cohort practicing differently? • Not only did they use epidurals less often, but • Used epidurals later • Spent more time with their patients in hospital--even though their patients spent less time in hospital • Indeed they practiced differently—more intimacy and engagement

11. But not the fault of the anesthesia establishment at BC Women’s or likely elsewhere. Anesthesia provides an excellent service. They help us resolve many problems It is we who ask for help!!!!!!!!! At least at BC Women’s, there is no evidence that anesthetists are scavenging for business There is evidence from rural family practice (Stuart Iglesias) that epidurals can be introduced and associated with lowering of Cxion rate But that study requires contextual or environmental analysis

12. The Tyranny of Meta-analysis And the misuse of Randomized Controlled Trials

13. Collateral damage or Blowby—think Iraq • Or throwing the mother (and at times the baby) out with the bathwater.

14. Cochrane Meta-analysis of Effect of Epidural Analgesia • Comparing Epidural to Narcotics • Previously meta-analyses showed a 10% increase in Cxion rate with epidural analgesia • Current Cochrane does not—why not? Is Cochrane wrong? • It is not the fault of the RCT as a methodology!! • It is the inclusion in the meta-analysis of studies that ought not to be there—or the studies need to be grouped or stratified according to their settings or approaches so one can know if the results apply to one’s own setting

15. Central Concepts in Applicability of EBM • Look at both the left and the right side of the equation • What about the “inadvertent” consequences of the approach or procedure addressed by the trial (right side) or what youare interested in compared to the left side?? or big picture

16. Length 1st Stage 4.3 hour increase with epidural

17. Length 1st stage 23.8 minutes with epidural

18. Length2nd stage 61 minutes increase with epidural

19. Length 2nd stage 61 minutes with epidural

20. OxytocinAugmentation 38% 52%

21. Oxytocin augmentation 43% 39%

22. Malposition 15% 7%

23. Malposition 17.8% 12.8%

24. Instrumentation 27% 16%

25. Instrumental delivery 19.3% 14.2%

26. Perineal trauma

29. Maternal hypotension

30. Maternal urinary retention

31. Fever 24% 6%

32. Fever 21.4% 5.9%

33. All studies: mixed parity, various concentrations of agents both study arms and mostly IM narcotic Cesarean 12-13% 10-14% 5% both arms 10.1% 7.8% Sharma: Dallas Parkland 12% base Cxion rate, low dose oxy augmentation, Randomization @4-5cms. Clark: Louisville, 70%>4 cms, high dose oxy, Loughan: London UK Randomization 3-4cms, Sharma!!!!

34. Cesarean section 10.9% 10.2%

35. 11% 7% Klein Sensitivity Analysis: retaining only those studies that randomized early at < 4-5 cms

37. Wong CA, Scavone BM, Peaceman AM, McCarthy RJ, Sullivan JT, Diaz NT, et al. The risk of cesarean delivery with neuraxial analgesia given early versus late in labor. N Engl J Med 2005;352: 655-65 • Authors and NEJM editorialist claimed that early epidurals do not increase the rate of caesarean deliveries. • The study was not of early epidural analgesia, and the oxytocin augmentation rate of 75% at first analgesia makes for lack of generalisability. • The claim that women need not worry that early epidurals will lead to increased caesareans is false.

38. This trial was about two methods of helping women with pain in early labour. • In the “epidural arm”, an epidural catheter was placed. On first request for analgesia, women received intrathecal fentanyl, and in the narcotic arm, hydromorphone. • On second request, almost two thirds of women in both arms were in active labour, 4 cm or more dilated. • In the intrathecal "epidural" arm, they received low dose epidurals; in the narcotic arm, hydromophone.

39. This trial, as others that have contributed to the Cochrane meta-analysis showed no increase in caesareans in the presence of epidural analgesia, but does not acknowledge that most women were in active labour at time of second request or when they actually got an epidural-- when most will do well. • Wong et al, like Sharma et al, the other major contributors to the Cochrane meta-analysis showing no difference, have shown only that when women's pain in the latent phase is managed with intrathecal, narcotic, or other pharmacological or non-pharmacological means, an epidural in the active phase of labour does not increase the rate of caesarean section.

40. Major Chinese TrialWang F. Anesthesiology. 111 (4) 20009. 871-880 Epidurals in the latent phase of labor, a 5 year RCT 12,793 nulliparous women randomized to epidural vs. meperidine in latent phase 1.6 cm vs 5.1 cm CS 23.2% vs 22.8% 75% oxytocin each arm, but reported only 23% each am AFTER 2nd request for pain meds. Industrialized birth—lacks external validity to most Canadian settings

41. 2007 Meta-analyses • Patient-requested Neuraxial Analgesia for Labor--Marucci et al Anesthesiology May 2007 • Review comes up with the same conclusions based on the same literature • New Cochrane meta-analysis same—before Wang Chinese trial. • All now state that early epidurals are not a problem

42. 2011 BJOG Meta-analysis Wassen MMLH et al online 6 studies met their criteria for inclusion Luxman 1998, small CS rates 6.6 and 10% Wong 2005 as above Ohel G et al 2006: 10-1@% CS rate Wang 2008 as above Wong 2009: induction only Conclude early epidural analgesia does not increase the CS rate

43. Epidural analgesia, while a superb technology, and the “best” form of pain relief has completely transformed normal birth--leading to a cascade of interventions. • 3 of 4 Canadian women receive one or more major procedures or interventions in labor (CIHI, 2004) and epidurals are a major contributor • Epidural Rate • 45.4% Canada, 45% Vancouver • 69% PQ • 60% Ont • 39% MB • 50% Alberta

44. Why don’t we acknowledge this? • Subversion by RCTs and EBM? • Cochrane reviews by • Anesthesiologists? • Nurse/Doctor’s comfort—we like it!! • Economics? • Existence of a dedicated anesthetic workforce that we created? • Not the fault of the anesthesia establishment!!!!! We asked for it • Women asked for it • (Think Twilight Sleep) • but we taught them to ask for it!

45. What is the nursing skill set to attend a woman with an epidural? What has happened to nursing since the advent of routine epidural analgesia?

46. From EBM to Research designed to deliver answers that we want to receive!From Evidence-based decision-makingTo what Philip Hall has called: • “Decision Based EvidenceMaking”

47. It is not the answers that are the problemIts the questions that are wrong!Compare epidural analgesia to narcotics but not to physiological birthStudy interventive, industrialized hospital births, not ideal midwifery managed physiological births

48. Whose evidence? • Does the study setting apply to me in my setting? • Basic problems with RCTs • Results apply only for the conditions of the trial (“Murray Enkin’s first law”) • Are conditions my conditions? • Do the participating practitioners practice the way that I practice?

49. Collateral damage or Blowby (2) • Example: Canadian Post-Term trial of expectant management vs induction at 41 weeks • Outside rarified atmosphere of the RCT, thinking that placenta degenerates at 41 3/7th weeks unleashes a cascade of “side effects” NO! EFFECTS--resulting in increased not decreased cxion rates and consequences for next pregnancy: 8% vs 44% cxion rate for nulliparous women at BC Womens

50. The Induction Cascade • Induction requires continuous electronic fetal monitoring because it is considered a “high risk” procedure. • This is because over-stimulation of the uterus can occur and that can lead to stress on the fetus. • Women receiving continuous electronic fetal monitoring are kept in bed almost all the time. • Immobility leads to abnormal progress of labor,