We would like to congratulate Briggs et al (1) for their work
highlighting a lack of dedicated pain teaching in undergraduate medical
studies. In light of the results it is unsurprising that pain is
inadequately managed in the hospital setting (2,3), with only 4% of UK
medical schools providing compulsory pain modules.
Whilst causes for a high prevalence of in-hospital patient pain are
m...
We would like to congratulate Briggs et al (1) for their work
highlighting a lack of dedicated pain teaching in undergraduate medical
studies. In light of the results it is unsurprising that pain is
inadequately managed in the hospital setting (2,3), with only 4% of UK
medical schools providing compulsory pain modules.
Whilst causes for a high prevalence of in-hospital patient pain are
multifactorial, it is important to note that this is partly a function of
the management delivered by all of the doctors responsible for the
patients' care, not just those recently graduated from medical school.
Inadequate assessment and treatment must therefore also relate to senior
doctor input, suggesting that the education gap established in medical
school fails to be addressed in the postgraduate setting. Awareness of
how medical schools fall short in providing pain teaching should prompt us
to address this problem in two ways: not just as the authors suggest by
developing the undergraduate curriculum, but also through addressing pain
education in postgraduate training and beyond.
In the UK the foundation program curriculum includes a comprehensive
section on pain, yet specialist training pathways vary in further pain
education requirements. Curriculum aside, it can be construed that methods
of delivering effective postgraduate pain education are likely
ineffective. The foundation program curriculum currently focuses on
functional prescribing of analgesia however this fails to necessarily
translate to safe knowledge on its use (4).
We were not surprised that methods of teaching at medical school were
principally classroom based, despite evidence to support alternative
methods (1). The meagre pain teaching sessions that junior doctors receive
in the hospital setting probably use similar classroom based methods and
may be inadequate to change practice and improve patient care. Our own
work has demonstrated that whilst knowledge based teaching in acute pain
management for foundation doctors improved their perceived confidence in
using morphine in an acute pain setting, it failed to change their
attitudes to strong opioids (5). These attitudes are a potential barrier
to effective prescribing of opioids (6), the mainstay of severe pain
management. Purely knowledge based interventions, which have been
highlighted by Briggs et al (1) as inadequate in the undergraduate setting,
are seemingly ineffective in changing doctor attitudes and practices, and
are failing to improve patient care. Novel approaches such as inter-
professional training (7) and interventions that address emotional and
reflective development (8) would be useful additions to pain education in
the postgraduate setting.
We have an obligation to our patients to ensure their pain is managed
to the best of our ability, yet this may be hindered by a lack
undergraduate education and training which remains wanting throughout our
medical careers. Perhaps it is time for us to see pain education as part
of continuous professional development. Briggs et al (1) have highlighted
that an excellent start is needed to put doctors on the right track.
However this could be entirely fruitless if early learning is not
maintained and supported throughout one's career as a whole.
References
1. Briggs E V, Battelli D, Gordon D, et al. Current pain education
within undergraduate medical studies across Europe: Advancing the
Provision of Pain Education and Learning (APPEAL) study. BMJ Open.
2015;5(8):e006984.
2. Helfand M, Freeman M. Assessment and management of acute pain in adult
medical inpatients: a systematic review. Pain Med. 2009;10(7):1183-99.
3. Dix P. Pain on medical wards in a district general hospital. Br J
Anaesth. 2004;92(2):235-7.
4. Harding S, Britten N, Bristow D. The performance of junior doctors in
applying clinical pharmacology knowledge and prescribing skills to
standardized clinical cases. Br J Clin Pharmacol. 2010;69(6):598-606.
5. Laycock H, Casely E, Bantel C. Knowledge, skills but not attitudes
change with pain education. In: Conference abstracts for Association for
Medical Education Europe Conference 2013: Colouring outside the lines.
2013 August 24-28; Prague, Czechoslovakia. Dundee: MedEdWorld: 2013.
Available from: http://www.amee.org/getattachment/Conferences/AMEE-Past-
Conferences/AMEE-Conference-2013/AMEE-2013-ABSTRACT-BOOK-updated-
190813.pdf
6. Kim M-H, Park H, Park EC, Park K. Attitude and knowledge of physicians
about cancer pain management: young doctors of South Korea in their early
career. Jpn J Clin Oncol. 2011;41(6):783-91.
7. Salam T, Saylor JL, Cowperthwait AL. Attitudes of Nurse and Physician
trainees towards an interprofessional simulated education experience on
Pain Assessment and Management. J Interprof Care. 2015;29(3):276-8.
8. Murinson BB, Nenortas E, Mayer RS, et al. A New Program in Pain
Medicine for Medical Students?: Integrating Core Curriculum Knowledge with
Emotional and Reflctive Development. Pain Med. 2011;12(2):186-95.
Having carefully read the letter by Donzelli et al., we would like
to thank the writers for the comments.
It is our intention to stick strictly to the results of our analysis and
not to address topics such as glycemic targets and benefit of vegetarian
diet in type 2 diabetes which have nothing to do with our paper.
By using a validated epidemiological methodology in a real life
population, our analysis aimed to see whe...
Having carefully read the letter by Donzelli et al., we would like
to thank the writers for the comments.
It is our intention to stick strictly to the results of our analysis and
not to address topics such as glycemic targets and benefit of vegetarian
diet in type 2 diabetes which have nothing to do with our paper.
By using a validated epidemiological methodology in a real life
population, our analysis aimed to see whether any greater risk of HF
hospitalization could be detected in DPP-4i users as compared to patients
on other type-2 diabetes treatments. We found no such increased risk, in
accordance with Fadini et al who, some weeks later, published similar
results in the European Heart Journal (1) and with the TECOS TRIAL (2)
(which can not be reported as a commercial trial because it was requested
and in part designed by the American agency FDA).
By the way, even though all-cause mortality was not the objective of our
work, we also found that it was 6% lower in DPP-4i users, whereas insulin
users showed an excess of risk for any type of hospital admission (19%)
and death (20%). These results support many speculative explanations in
favor (or against) DPP-4i utilization. We thought it could make sense to
remember that specialty care is associated with reduced mortality and
since DPP-4i are mostly prescribed by diabetologists, this should be
considered. In favor of DPP-4i class, we could have speculated that these
medications, before the SAVOR TIMI negative findings on HF, were on
purpose prescribed in patients at higher risk of cardiovascular disease
because they were held safe.
We acknowledge that the specialty could also have blunted a possible
slight negative effect on HF of DPP-4i, however we would like to stress
that our findings (OR for admission for HF 1.00 [0.94-1.07], incident
HF1.01 [0.92-1.11], recurrent HF 1.02 [0.84-1.22]) can not be defined
"...slightly increased OR..." but neutral, non-significant ORs.
Our statistician is back on duty from September 14th and we are willing to
share the databases for further analysis. However, as it seems that the
authors of the letter intend to calculate ORs adjusted for insulin use, we
wonder if they have misunderstood the results presented in our paper. ORs
are already adjusted for insulin/glimepiride/glibenclamide use, as
well as for other confounders reported in table 2.
References
1. Fadini GP, Avogaro A, Degli Esposti L, Russo P, Saragoni S, Buda
S, Rosano G, Pecorelli S, Pani L; OsMed Health-DB Network. Risk of
hospitalization for heart failure in patients with type 2 diabetes newly
treated with DPP-4 inhibitors or other oral glucose-lowering medications:
a retrospective registry study on 127,555 patients from the Nationwide
OsMed Health-DB Database. Eur Heart J. 2015 Jun 25. pii: ehv301. [Epub
ahead of print]
2. Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, Josse R,
Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Pencina MJ, Standl E,
Stein PP, Suryawanshi S, Van de Werf F, Peterson ED, Holman RR; TECOS
Study Group. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2
Diabetes. N Engl J Med. 2015 Jul 16;373(3):232-42. doi:
10.1056/NEJMoa1501352. Epub 2015 Jun 8.
We read this article with great interest and would like to
congratulate the authors on conducting an evidence based study on
effectiveness, safety and cost of orphan medicinal products. Laboratoires
CTRS is a pharmaceutical company specialising in orphan medicinal
products.
We would like to correct certain inaccurate information within this
article concerning Laboratoires CTRS' medicinal product Orphacol (choli...
We read this article with great interest and would like to
congratulate the authors on conducting an evidence based study on
effectiveness, safety and cost of orphan medicinal products. Laboratoires
CTRS is a pharmaceutical company specialising in orphan medicinal
products.
We would like to correct certain inaccurate information within this
article concerning Laboratoires CTRS' medicinal product Orphacol (cholic
acid):
- In the Appendix 1, Orphacol is not listed as an approved medicinal
product, although it is licensed since 12 September 2013.
- In the same table, a different medicinal product containing cholic
acid, i.e., Cholic acid FGK, is listed. However, the reference associated
with that product (number 13) concerns Orphacol.
- In the Appendix 2 table, Orphacol is listed with a wrong
indication. Orphacol is approved for the treatment of inborn errors in
primary bile acid synthesis due to 3beta-Hydroxy-delta5-C27-steroid
oxidoreductase deficiency or delta4-3-Oxosteroid-5beta-reductase
deficiency in infants, children and adolescents aged 1 month to 18 years
and adults. In addition, the "Summary of main results" is very unclear, as
the evaluated parameter is not specified.
- We note that the marketing authorisation for Cholic acid FGK
(renamed to Kolbam) has recently been withdrawn following a judgement of
the General Court of the European Union.
We would like to take this opportunity to comment on two main aspects
of this article, i.e. the level of evidence available for very rare
conditions and the treatment cost, from the specific perspective of
Orphacol.
Evidence
The diseases treated by Orphacol are extremely rare: In the United
Kingdom, there are a total of 8 to 10 patients and in the European Union,
we estimate that there are about 90 patients with 3beta-Hydroxy-delta5-C27
-steroid oxidoreductase deficiency and 15 patients with delta4-3-
Oxosteroid-5beta-reductase deficiency. The treatment with cholic acid had
been established as effective and safe in over 15 years of clinical use at
the time of application for marketing authorisation. While the extremely
small patient numbers already make the conduct of any clinical study very
challenging, a controlled clinical trial would be unethical as withholding
the effective cholic acid treatment exposes patients to a risk of liver
damage or even death.
In this context, which is common for ultra-orphan conditions such as
those treated by Orphacol, applying a "one size fits all" application of
OCEBM and GRADE criteria for the assessment of clinical evidence is not
meaningful. The Orphacol marketing authorisation application included data
on each of the approximately 60 patients identifiable and described in the
literature, and detailed treatment data (albeit not from a prospective
clinical study) for 15 of them. The treatment effects were strong and
highly consistent, demonstrating that cholic acid treatment changed the
patients' prognosis from a certain need for a liver transplantation to a
completely normal life. We believe that within the context of the disease,
the quality and strength of the overall body of evidence for Orphacol was
as strong as it could possibly be. The French Health Technology Assessment
body (the Commission de la Transparence at the Haute Autorite de la Sante)
has notably shared this approach as well as conclusion and has recognised
Orphacol as a major improvement of patient care. In addition, the
reputable journal Prescrire, specialised in the evaluation of medicinal
products, did the same and has declared Orphacol a major therapeutic
progress.
Cost
The article cites the cost of orphan medicinal products for which
similar generic or unlicensed drugs (known as "Specials" in the UK) exist
(see Figure 5 and related paragraphs). It must not be surprising that
unlicensed medicines are cheaper as compared with the licensed medicines
as the EU marketing authorisation obligatory for designated orphan
medicinal products come with substantial obligations, designed to
safeguard patient safety, for the licence holder. In addition, there is a
significant cost associated with the licensing process itself. Orphacol is
an example of an ultra-orphan medicinal product for which unlicensed
versions exist or have existed. Laboratoires CTRS does not claim
Orphacol's price to be justified by research and development costs, as the
application for Orphacol was based on literature data. The price
differential is rather justified by the costs of producing extremely small
volumes of a medicinal product that complies with the applicable rules of
Good Manufacturing Practice; of complying with the post-approval
obligation of maintaining a treatment database including all patients
treated with Orphacol; and of the applicable pharmacovigilance
obligations. In particular the obligations related to pharmacovigilance
are very onerous, as they apply within the entire European Union,
irrespective of the existence of patients affected in any given member
state or of whether the medicinal product is marketed. The resulting
aggregate costs can only be spread over a very small overall sales volume.
In the case of Orphacol, we estimate that these aggregate costs are about
ten times higher than the costs of producing an unlicensed version (such
as a "Special" in the United Kingdom) which does not have to follow all
the regulatory obligations mentioned above. Laboratoires CTRS needs to
make a medicinal product that complies with all regulatory obligations
available, doing so in a financially sustainable manner.
Conclusion
The inaccuracies that we have pointed out should be corrected. We
believe that supporting evidence and cost of orphan medicinal products
should be considered in more detail in further investigations, taking into
consideration the additional aspects that we have outlined.
Conflict of Interest:
The authors are employees and stockholder (A. Ferry) of Laboratoires CTRS.
This article by Cunningham et al. on cervical cancer screening and
HPV vaccine acceptability is a large population based study that collected self-reported responses - the authors mentioned the same as a
study limitation.
However, by detailed reading of Table 4, it appears that respondents who
had not heard of the HPV vaccine were asked about attitudinal questions
like 'willing to definitely accept the HPV vaccine', 'beli...
This article by Cunningham et al. on cervical cancer screening and
HPV vaccine acceptability is a large population based study that collected self-reported responses - the authors mentioned the same as a
study limitation.
However, by detailed reading of Table 4, it appears that respondents who
had not heard of the HPV vaccine were asked about attitudinal questions
like 'willing to definitely accept the HPV vaccine', 'believes
husband/partner will definitely accept HPV vaccine', 'believes
family/friends will support the HPV vaccine', 'believes they are able to
access a clinic/doctor for vaccination', 'believes vaccines are
beneficial', 'willing to pay for vaccines', etc. Response against these
questions are invalid. Therefore the interpretation of Table 4
is erroneous. Moreover these responses are going to introduce various
biases, such as yes saying bias, faking bad bias, faking good bias, etc.
All these were not mentioned in the study. Further examination of the study
tool, i.e. the interview schedule will confirm the validity of this study.
Equation 2 that describes the change in the pure tone average of 2000, 3000, and 4000 Hz appears to be mistaken. The correct equation should be
Women: PTA234 = (0.0002222*(Age.^3)) - (0.02262*(Age.^2)) + (0.9563*Age) - 10.99;
The quadratic coefficient as published "-0.0262" yields a curve that does not fit the Annex B4 ISO 1999:2013 data.
There is a small mistake in the abstract of this
manuscript.
The hazards ratios (HR) for mortality in the abstract are not
consistent with the result section and Table 5. The correct sentence would
be:
Mortality of UBC was not increased for patients with either type 1
(HR = 0.79 (95% CI 0.32 to 1.94)) or type 2 diabetes (HR = 1.05 (95% CI
0.83 to 1.33)).
There is a small mistake in the abstract of this
manuscript.
The hazards ratios (HR) for mortality in the abstract are not
consistent with the result section and Table 5. The correct sentence would
be:
Mortality of UBC was not increased for patients with either type 1
(HR = 0.79 (95% CI 0.32 to 1.94)) or type 2 diabetes (HR = 1.05 (95% CI
0.83 to 1.33)).
Martin Frisher in his letter 'Harmful consumption of alcohol among
people aged 50 or over in England'
(http://bmjopen.bmj.com/content/5/7/e007684.abstract/reply#bmjopen_el_9271)
in response to my article 'Socioeconomic determinants of risk of harmful
alcohol drinking among people aged 50 or over in England'
(http://bmjopen.bmj.com/content/5/7/e007684.full) notes that in a careful
study published shortly after mine (http:...
Martin Frisher in his letter 'Harmful consumption of alcohol among
people aged 50 or over in England'
(http://bmjopen.bmj.com/content/5/7/e007684.abstract/reply#bmjopen_el_9271)
in response to my article 'Socioeconomic determinants of risk of harmful
alcohol drinking among people aged 50 or over in England'
(http://bmjopen.bmj.com/content/5/7/e007684.full) notes that in a careful
study published shortly after mine (http://www.biomedcentral.com/1471-
2458/15/703), he and his co-authors failed to find any significant
association between any pattern of current alcohol consumption and poor
self-rated health, implicitly casting doubt about the usefulness of
guidelines and recommendations regarding limits, and categorisations often
used in academic and non-academic literature including 'harmful',
'hazardous', or 'sensible' drinking.
Frisher cites an official document published in 1995 by the UK Government
(Department of Health) when acknowledging that 'harmful' drinking is
defined in relation to a given threshold. This is still the case: the
former Coalition government published what to this day is the latest
official policy paper on the topic: '2010 to 2015 government policy:
harmful drinking', first published in 2013 but updated in May 2015. In
that document, 'harmful drinking' is defined in terms of daily alcohol
units consumed. Furthermore, as also detailed in my paper, NICE (the
National Institute for Health and Care Excellence) also defines risk in
relation to units. Nevertheless, in my paper, I also mention that
resorting to a fixed number of units is not without problems but explain
that I have adopted it because one of the objectives of the paper was to
influence 'policymakers and practitioners in England who have to follow
NICE guidelines' (p.4).
Regarding Frisher et al's main result, that 'there were no drinking
profiles associated with significantly higher rates of poor self-rated
health relative to occasional drinkers', I do not see it as a
contradiction with or a refutation of the results reported in my paper.
An informative result in itself, it may as well suggest that self-rated
health status does not necessarily reflect either risk or the actual
presence of a health condition. That is, the risk or the harm may be
present but is not captured by self-reported levels of health status.
This is not new. Just to mention one example, Fink et al
(http://onlinelibrary.wiley.com/doi/10.1046/j.1532-5415.2002.50467.x/pdf)
reported that in their sample only 17 per cent of people aged 65 or over
reported fair or poor subjective health, whilst one hundred percent of
them had at least one morbidity potentially caused or worsened by alcohol
use.
I would encourage Frisher's team and other researchers to look into
longitudinal effects of alcohol consumption above different thresholds on
health conditions, not just on self-reported health.
In their article,[1] Milliken et al point to the absence of
transparency in the pan-Canadian Pharmaceutical Alliance (pCPA). However,
their analysis also lacks clarity. First, they do not provide details of
the drugs included in their pre-pCPA group so that it is impossible to
assess whether they are comparing apples with oranges, which is a common
failing of before/after study designs.
In their article,[1] Milliken et al point to the absence of
transparency in the pan-Canadian Pharmaceutical Alliance (pCPA). However,
their analysis also lacks clarity. First, they do not provide details of
the drugs included in their pre-pCPA group so that it is impossible to
assess whether they are comparing apples with oranges, which is a common
failing of before/after study designs.
A second and more important lack of transparency results from
aggregating drugs given full listing status with those that received
coverage subject to special criteria. Unless a drug is a 'me-too' product
joining a class of drugs that already has full coverage (e.g. Lodalis in
Milliken et al's Appendix 1), almost all drugs selected for listing only receive financial coverage subject to specific clinical conditions (a
situation that applies to all the other drugs in Appendix 1). If the
access conditions are well designed with the participation of all
appropriate stakeholders, they allow a new drug to be targeted to patients
most likely to receive benefit.
However, access criteria are often not established with input from
physicians and patients and, as a result, few patients are eligible for
insurance coverage under the respective provincial government plan. All
too often this situation occurs with expensive new drugs for rare
disorders.[2] For example, Kuvan for phenylketonuria in Milliken et al's
Appendix 1, which is now listed in the Ontario and Saskatchewan drug
plans, has access criteria that are extremely restrictive and not evidence
-based and no patient has yet to meet the criteria.[3] Thus, provinces may
'list' a drug as having restrictive coverage, but this does not
necessarily equate with patient access. Future analyses need to separate
drugs with restricted access from those with full coverage.
As Milliken et al note, the pCPA needs to improve the transparency of
its policies, processes, decisions, criteria and timelines.[4] The pCPA
does not have its own website, just a page on the site used by Canada's
provincial premiers to communicate a variety of issues to their
constituents.[5] The premiers report that pCPA negotiations have 'resulted
in over $315 million in combined savings annually'. It is not known where
these savings go. They should be used to improve provincial drug plan
access, especially access to drugs for rare disorders.
References:
1. Milliken D, Venkatesh J, Yu R, et al. Comparison of drug coverage in
Canada before and after the establishment of the pan-Canadian
Pharmaceutical Alliance. BMJ Open 2015; 5:e008100.
2. Update: what's happening with Ontario's Interim Funding for eculizumab.
Brampton, ON: aHUS Canada, 2015. Available online at: http://www.ahuscanada.org/update-
whats-happening-with-ontarios-interim-funding-for-eculizumab (Last accessed 25th
September 2015).
3. Adams J. No patient access to only drug for PKU: have government drug
plans been ignoring CDR? Poster presentation, Canadian Agency for Drugs
and Technologies in Health Symposium, Saskatoon, April 2015.
4. Rawson NSB. Access delayed, transparency denied. Vancouver: Fraser
Institute, 2014. Available online at: http://www.fraserinstitute.org/article/access-
delayed-transparency-denied (Last accessed 25th September 2015).
5. The pan-Canadian Pharmaceutical Alliance. Ottawa: Council of the
Federation Secretariat, 2015. Available online at:
http://www.pmprovincesterritoires.ca/en/initiatives/358-pan-canadian-
pharmaceutical-alliance. (Last accessed 25th September 2015).
I would like to make a correction to the funding list on our
recently published paper "Association of 12 h shifts and nurses' job
satisfaction, burnout and intention to leave: findings from a cross-
sectional study of 12 European countries"
The correct list should be:
European Union's Seventh Framework Programme (FP7/2007-2013,
grant agreement no. 223468; WS and LHA), National Institute of
Nursing Resea...
I would like to make a correction to the funding list on our
recently published paper "Association of 12 h shifts and nurses' job
satisfaction, burnout and intention to leave: findings from a cross-
sectional study of 12 European countries"
The correct list should be:
European Union's Seventh Framework Programme (FP7/2007-2013,
grant agreement no. 223468; WS and LHA), National Institute of
Nursing Research, National Institutes of Health (R01NR04513; LHA), the
Norwegian Nurses Organisation and the Norwegian Knowledge Centre
for the Health Services (IMH), Swedish Association of Health
Professionals, the regional agreement on medical training and clinical
research between Stockholm County Council and Karolinska Institutet,
Committee for Health and Caring Sciences and Strategic Research
Program in Care Sciences at Karolinska Institutet (CT), Spanish
Ministry of Science and Innovation (FIS PI080599; TM-C).
The current research was part funded by the
National Institute for Health Research Collaboration for Leadership in
Applied
Health Research and Care (NIHR CLAHRC). The views expressed in this
publication are those of the author(s) and not necessarily those of the
NHS,
the National Institute for Health Research or the Department of Health.
The August 11 response of Dr. Elard Koch and several co-authors fails to rectify the two major flaws in their study that I exposed in my April 9 rebuttal, and in fact, further confirms those flaws. Their very lengthy response also ignored many of my arguments and repeated many of their disputed points.
This reply explains why those two major errors remain fatal to their study's conclusions. I then address the question of anti...
The August 11 response of Dr. Elard Koch and several co-authors fails to rectify the two major flaws in their study that I exposed in my April 9 rebuttal, and in fact, further confirms those flaws. Their very lengthy response also ignored many of my arguments and repeated many of their disputed points.
This reply explains why those two major errors remain fatal to their study's conclusions. I then address the question of anti-abortion bias, which I believe played a key role in the flawed design of the study. To be fair, I also address my own biases. Finally, I deal with several ancillary issues arising from Koch et al.'s response (for those interested to read on).
FATAL FLAWS ARE STILL FATAL
My rebuttal had explained that abortion law was not related to abortion practice in Mexico, and that this invalidates the study's methodology and conclusion. That's because you can't hypothesize a possible effect on abortion mortality based on the existence or absence of various legal exemptions across Mexican states, when those exemptions don't even work. In practice, few Mexican women can access abortions under the legal exemptions. In response, Koch et al. confirmed this flaw by saying: "...between states, legal permissiveness may be the same, but accessibility may differ by multiple unmeasured factors. We do not say nor have we stated that we are using this term as a proxy for greater or less accessibility to pregnancy termination..." But their failure to account for the difference between law and practice IS THE FLAW. Their methodology implicitly assumed that abortion restrictions reflect abortion practice, but since they now concede that's not the case, their conclusion that maternal mortality is unrelated to the presence or absence of certain abortion restrictions is meaningless.
I had shown that it was arbitrary and erroneous to select, in particular, the legal exemption for abortion in cases of genetic or congenital malformation as the criterion for assigning Mexican states to the categories of "more permissive" or "less permissive" abortion legislation, depending on whether the state had that exemption. The rarity of abortion for fetal abnormality makes this variable useless as a proxy, because the miniscule numbers of maternal deaths that may result would be impossible to detect statistically in order to compare states with and without the exemption. The authors' only response is to argue that such abortions may be slightly less rare than I claim, based on the low prevalence of Down???s syndrome at birth in several other countries. But that has nothing to do with Mexico or the fact that abortions for any kind of serious fetal abnormality are in the range of 1% of all abortions in countries where abortion is widely legal. So their error remains, especially since abortions due to fetal abnormality are likely even rarer in Mexico than in western countries because of its restrictive laws, inaccessibility of legal abortion under the exemptions, profound stigma, and physician refusals.
The authors say that exploratory analyses are "valid and valuable tools to avoid an arbitrary categorization." But somehow, that's exactly what they ended up with. The authors confirm their flaw by explaining that they selected the legal exemption for fetal abnormality as the main variable because it was the only one that yielded an association with maternal mortality, as well as the only one where the 32 Mexican states had a roughly equal distribution in terms of whether they had the exemption or not. In other words, the variable was arbitrarily selected on the basis of convenience and because it happened to yield an association that I've already shown is meaningless. (Correlation does not equal causation.) A random association is easy to find if you conduct a fishing expedition for one amongst a host of variables, but one should not then base an entire study on it and draw conclusions from it.
AUTHOR BIAS
Nine out of ten authors of the BMJ Open study had an undisclosed bias because they are signatories to the "Dublin Declaration." (http://www.dublindeclaration.com/signatories/) This document denies the need for legal abortion even to save a woman's life. Notably, the peer review process for their BMJ Open study failed to catch the substantive errors in the study because neither peer reviewer had expertise in the subject matter, and one (R. Lieva) appears to hold the same position as the authors. (http://www.thelancet.com/journals/lancet/article/PIIS0140- 6736%2810%2961251-2/abstract)
The study contains repeated citations (over 30) of the authors' own past research on abortion and lists over a dozen references from Koch and various co-authors. The effect is to create a false picture of scientific confusion and conflicting data in the abortion field. This same pattern is repeated in their reply to me, even though several of their studies have been criticised. (Here's a compendium of rebuttals to their work: http://choice-joyce.blogspot.ca/2012/08))
Koch et al. have gone to great lengths (in this and other studies) to try and show that factors such as access to emergency obstetric care have the greatest apparent impact on maternal mortality, not abortion laws. But their focus on maternal deaths, while important, obscures all the other suffering and harms that criminal abortion laws cause to women, including high complication rates from unsafe abortion (about 159,000 women are hospitalized annually in Mexico: http://www.guttmacher.org/pubs/Unintended -Pregnancy-Mexico.html). The implication is that we should accept this human cost as long as good health care systems can save women's lives in the end. Presumably the authors would disagree, and hopefully their implication was unintentional.
Given the overwhelming global and historical evidence of the danger posed to women by criminal abortion laws, (http://www.who.int/reproductivehealth/publications/unsafe_abortion/9789241501118/en/ and http://www.ncbi.nlm.nih.gov/pubmed/1949105 and numerous other sources) any study that concludes that restrictive abortion laws do not contribute to maternal mortality should be treated with suspicion.
But let me turn now to the question of my own biases, since Koch et al. would presumably claim that I'm the one who's biased, as well as unscientific. This is apparent from the authors' near ad hominem treatment of my criticisms, dismissing them as "based largely on personal opinions or speculative assumptions," and "not scientifically based." I'm a writer and pro-choice activist, not a scientist. I do not apologize for my impassioned defense of women's rights and lives. I've been monitoring the anti-choice movement for 25 years and Koch's work for 3 years.
For the record, I did not have "discomfort" with the study's findings, because I recognized the study methodology and conclusions were deeply flawed. However, I did feel offended by the study. I object to its very premise and even that it was published in a reputable scientific journal where it does not belong. Please allow me to explain.
I have a bias in favour of the belief that women deserve equality, human rights, and dignity. I also have a bias against criminalizing life- saving healthcare that only women need. Should such biases, if expressed, lessen my credibility or weaken my arguments? If so, it must be because it's still up for debate whether women deserve human rights and freedoms, including the fundamental right to control their fertility.
ADDENDUM: ANCILLARY ISSUES
Unsafe Abortion as a Contributing Factor to Maternal Mortality:
The authors protest my "unsubstantiated and dissociated" suggestion that they are using other contributing factors to maternal mortality as a smokescreen to cover up the effect of unsafe or illegal abortion. Their objection is largely answered by my points above on author bias.
Further, I believe the authors are being disingenuous when they say they want to emphasize the other factors that contribute to women suffering and dying in childbirth from preventable causes. Rather, they appear to be primarily concerned with abortion. Their study's title begins with "Abortion legislation" as the key factor. The study objective is: "To test whether there is an association between abortion legislation and maternal mortality outcomes after controlling for other factors thought to influence maternal health." Their press release for the study (http://www.melisainstitute.org/pr-18022015-english.html) opens with: "Laws protecting the unborn and therefore, less permissive in regard to abortion, bear a negative ...connotation, because induced abortion in clandestinity might increase maternal deaths. However, a new study conducted in 32 Mexican states ...challenges this notion..." And most of their other research focuses on abortion.
Of course, many factors contribute to maternal mortality, and many effective ways exist to address it. But as I said in my rebuttal, this range of other factors could swamp the effect of unsafe abortion on maternal mortality rates and make it harder to detect statistically, particularly if a country's mortality rate from unsafe abortion is relatively low compared to other countries. The study methodology the authors employed was almost guaranteed to find no meaningful association anyway, which allowed them to present their foregone conclusion that abortion laws don't affect maternal mortality.
Clandestine abortion is still a major cause of maternal mortality in many parts of the world, particularly in Africa and Asia. (http://www.prb.org/pdf11/abortion-facts-and-figures-2011.pdf) It is unusual for developing countries with strict bans on abortion to have relatively low maternal mortality rates. In such countries (like Chile and a handful of others in Latin America), other factors indeed play an important role including widespread use of misoprostol - however, maternal mortality would almost certainly be even lower if abortion was legal, safe, and accessible. Regardless, complications from unsafe abortion remain high throughout Latin America and the Caribbean, with over one million women hospitalized annually - 159,000 in Mexico alone during 2009 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557184/ and http://www.guttmacher.org/pubs/Unintended-Pregnancy-Mexico.html). This demonstrates that restrictive abortion laws continue to pose a great danger to women in Mexico, even if fewer are dying than in the past.
Issues with Vital Statistics for Abortion Deaths:
The authors' arguments that Mexico does not have a problem with underreporting or misclassification of abortions and associated mortality are unpersuasive. They put a lot of faith in vital statistics from the Mexican government - their only source - but it's unlikely that government statistics are as robust and accurate as they claim. The authors can only cite their own research as support. I found mentions in several studies (listed below) about the problems of misclassification and underreporting associated with the use of vital statistics when it comes to abortion, even in countries like Mexico that have otherwise high-quality records for maternal mortality.
In settings like Latin America where abortion is mostly illegal and highly stigmatized, women and their families would be more likely to not report or misreport an abortion, and health care personnel would be more likely to misclassify causes of death out of ignorance, fear, or compassion. For example, even with the existence of specific ICD codes for "Abortive Outcomes" (ICD-10 O00 to O08), why should we exclude the possible misclassification of unsafe abortion deaths under the codes for sepsis or hemorrhage in early pregnancy (ICD-10 O20 and O23)?
Vital statistics should not be relied upon alone to determine maternal mortality from unsafe abortion. Reputable studies employ a variety of sources and methods, including studies, hospital data, various types of surveys, and more. For no valid reason, Koch et al. neglect and dismiss these additional methodologies, while their own narrower methodology for estimating abortion incidence has been questioned. (http://www.guttmacher.org/media/resources/response-to-methodology- critique.pdf)
Recent studies on maternal death from unsafe abortion do not support Koch et al's claim that the rate for Mexico is as low as 3% of all maternal mortality. Before looking at these other figures, it's important to understand that studies and official statistics on maternal mortality rates and causes do not always distinguish adequately between deaths from induced abortion and spontaneous abortion (miscarriage), or even other "abortive outcomes" such as ectopic or molar pregnancies and other "unspecified" complications. However, we know that maternal deaths from miscarriage, legal abortion, and molar pregnancy are all very rare, at least in settings with reasonable access to health care. While ectopic pregnancies carry a higher risk of death, they are far less common than abortion or miscarriage. Therefore, the majority of officially-recorded abortion deaths in countries with restrictive laws are plausibly due to unsafe induced abortion, including many coded under other "Abortive Outcomes."
The following studies provide rates of maternal mortality due to abortion in Latin America and/or Mexico. The data for Mexico appear to be sourced from vital statistics only, except for #3, which also cites the WHO Mortality Database (in the study's Appendix).
1. The Schiavon et al. estimate for Mexico was 7% for 2008. (http://www.ncbi.nlm.nih.gov/pubmed/22920626)
2. A May 2014 global analysis by the World Health Organization (WHO) (http://www.thelancet.com/pdfs/journals/langlo/PIIS2214-109X%2814%2970227- X.pdf) provided an estimate of 9.9% for Latin America and the Caribbean. For Mexico, the study shows a rate of almost 8% as denoted on a bar graph in the Appendix (page 36). (http://www.thelancet.com/cms/attachment/2014592567/2036073535/mmc1.pdf)
3. A September 2014 study by IHME, the Institute for Health Metrics and Evaluation, shows in bar graphs an average rate of about 17.5% for Latin America and the Caribbean in 2013 (Figure 6, http://www.thelancet.com/action/showFullTextImages?pii=S0140- 6736%2814%2960696-6), and a rate of about 11% for Mexico (Appendix, page 127: http://www.thelancet.com/cms/attachment/2019762887/2039744952/mmc1.pdf).
Why are these data from Mexico (7%, 8%, and 11%) higher than Koch et al's estimate of 3%? It appears it's because Koch et al. excluded deaths coded under ICD-10 O00, O01, O02, and O08 (respectively: ectopic pregnancy, molar pregnancy, other abnormal products of conception [including missed abortion], and complications following abortion and ectopic and molar pregnancy). Excluding these codes could omit many unsafe abortion deaths that were misreported or misclassified.
GLOBAL RATES: The oft-cited 2008 WHO figure of 13% for global maternal mortality due to unsafe abortion (http://apps.who.int/iris/bitstream/10665/44529/1/9789241501118_eng.pdf) should be retired due to the new WHO analysis (#2 above). That study provides a figure of 7.9% globally for 2003 to 2009, with the reduction due to the use of recent data and improved methods. I would suggest that the reduced figure may also reflect the increased use of safer medical abortion by women in some regions.
Using a somewhat different methodology, the IHME study (#3 above) yields an estimate of about 15% global maternal mortality from abortion in 2013 (see Table 2, page 995: http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736%2814%2960696- 6.pdf). The variance with the WHO figure of 7.9% is unexplained.
INCIDENCE OF UNSAFE ABORTION: This report: http://www.guttmacher.org/pubs/Unintended-Pregnancy-Mexico.pdf was the source for my figures on the significant number of unsafe abortions and complications in Mexico (over a million abortions a year, and 159,000 hospitalizations). These numbers are higher than the estimates from Koch et al. because the latter are based only on vital statistics data, which is insufficient.
Medical Abortion:
The authors state: "It is self-contradictory to say that unsafe abortions have increased substantially over the last decades while observing substantial reductions in deaths from this cause." Unsafe abortions have increased globally in recent years but not substantially (from 19.7 million in 2003 to 21.6 million in 2008). But in Latin America, unsafe abortions DECREASED by a third between 1990 and 2008, and maternal mortality went down 70%. (http://apps.who.int/iris/bitstream/10665/75173/1/WHO_RHR_12.01_eng.pdf)
This dramatic reduction in maternal deaths coincides with the widespread availability of medical abortion (using misoprostol) in Latin America over the last two decades. In contrast, maternal mortality from unsafe abortion remains high in regions where misoprostol is not as easily attainable, such as Africa. This suggests that misoprostol plays a significant role in reducing women's deaths.
Several studies and reports also attribute the reduction in maternal deaths in Latin America to the increased use of medical abortion (such as: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557184/). This method has largely replaced more dangerous traditional methods, although it can still lead to a high rate of mostly non-lethal complications when used without medical supervision.
Koch et al. are unsatisfied however, and want to see an epidemiologic study with evidence that misoprostol decreases unsafe abortion mortality "independently of other major factors such as access to emergency obstetric care." This seems to be an unreasonable expectation given the swamping effect those factors would have on the detection of unsafe abortion mortality, especially if the study plugs in artificially low death rates from abortion.
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