Disclosure of conflicts of interest in Japanese randomized controlled
trials
Dear Editor,
Disclosure of potential conflicts of interest (COI) is essential in
interpreting randomized controlled trials with less risk of bias. In
2008, the Japanese Ministry of Health, Labour and Welfare issued an
ethical guideline for clinical research that endorsed disclosure of
potential COI 1. To assess impact of the gu...
Disclosure of conflicts of interest in Japanese randomized controlled
trials
Dear Editor,
Disclosure of potential conflicts of interest (COI) is essential in
interpreting randomized controlled trials with less risk of bias. In
2008, the Japanese Ministry of Health, Labour and Welfare issued an
ethical guideline for clinical research that endorsed disclosure of
potential COI 1. To assess impact of the guideline, we investigated the
proportion of Japanese randomized controlled trial articles which
disclosed COI published during 2009-2010.
We used ICHUSHI Web 2, the largest database of medical literature in
Japan run by the Japan Medical Abstracts Society, to identify articles
with the following characteristics; post-marketing, double-blind,
randomized controlled trial of prescription drugs; published by official
journals of medical associations belonging to the Japanese Association of
Medical Science; conducted in Japan and by public research institute
(i.e., not by pharmaceutical company).
We identified 18 articles which met the above criteria. Funding
source(s) was disclosed in 56% (10/18). Pre-registration was indicated in
17% (3/18). Study endpoint was clearly specified in 50%. Most trials
(88%) reported results favoring trial drugs over comparator drugs or
placebo.
The 18 articles were published in 14 journals. In submission
requirements of these journals during 6-12 months prior to the
publication, disclosure of potential COI was requested in 43% (6/14). It
was requested in 55% (6/11) of journals written in English and 0% (0/3) in
Japanese.
These findings suggest that Health Ministry's guideline has not taken
full effects, and that caution should be practiced in interpreting
Japanese randomized controlled trials for their financial and scientific
integrity.
References
1. Ministry of Health, Labour and Welfare. ethical guideline for clinical
research,2008(http://www.mhlw.go.jp/general/seido/kousei/i-kenkyu/#4)
2. Japan Medical Abstracts SocietyVer.4(http://www.jamas.or.jp/)
One third of patients who undergo surgery will experience
postoperative nausea and vomiting (PONV) which can be very distressing
(wound dehiscences and pulmonary complications)[1].
Rawlinson and colleagues [2] have made an excellent systematic review of
randomised controlled trials, whose conclusions included the confirmation
of intravenous dexamethasone and ondansetron (5-HT3 antagonist) as
effective...
One third of patients who undergo surgery will experience
postoperative nausea and vomiting (PONV) which can be very distressing
(wound dehiscences and pulmonary complications)[1].
Rawlinson and colleagues [2] have made an excellent systematic review of
randomised controlled trials, whose conclusions included the confirmation
of intravenous dexamethasone and ondansetron (5-HT3 antagonist) as
effective drugs for prophylaxis of PONV when compared to controls.
However, a recent FDA safety alert [3]refers that a single 32 mg
intravenous dose of ondansetron may affect the electrical activity of the
heart (QT interval prolongation), which could predispose patients to
develop an abnormal and potentially fatal heart rhythm known as "torsades
de pointes". Additionally, ondansetron is a very expensive drug, which in
the present financial crisis is very relevant.
So, it may be useful to remember the old and low-priced antiemetic
metoclopramide as a cheaper and safer alternative to ondansetron.
Metoclopramide has not yet been associated with "torsades de pointes". As
it blocks dopaminergic (D2) receptors, it is contraindicated in
Parkinson's disease, and with chronic use may induce extrapyramidal
reactions. But, for a single or short therapeutic course this problem
seems not frightening, and furthermore, it has the advantage to increase
GI motility, which may be useful to reduce the opioid gastric side
effects, and if used before anaesthesia induction, it may also mitigate
the danger of gastric content aspiration.
Reference
1- Apfel CC, Korttila K, Abdalla M, et al. A factorial trial of six
interventions for the prevention of postoperative nausea and vomiting. N
Engl J Med 2004;350:2441-51.
2- Evid Based Med. 2012;17(3):75-80.
3- FDA at:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm272041.htm
In this week's EBM, Bond and colleagues report a systematic review
entitled: 'Psychological consequences of false-positive screening
mammograms in the UK'.(1) Their two main outcomes are self-reported
questionnaires, and attendance at the next screening round.
Together with two colleagues, I conducted a systematic review in 2004
on the adequacy of measurement of short and long-term consequence...
In this week's EBM, Bond and colleagues report a systematic review
entitled: 'Psychological consequences of false-positive screening
mammograms in the UK'.(1) Their two main outcomes are self-reported
questionnaires, and attendance at the next screening round.
Together with two colleagues, I conducted a systematic review in 2004
on the adequacy of measurement of short and long-term consequences of
false-positive screening mammography.(2) We concluded that the generic
measures (GHQ, HADS and STAI) "should not be used to measure psychological
consequences of any kind of cancer screening" and that a condition-
specific measure (PCQ) was preferable.(2) We also concluded, "Given the
inadequacy of the measurement instruments used, any current conclusions
about the long-term consequences of false-positive results of screening
mammography must remain tentative."(2) Therefore, we conducted six focus
group interviews to test the content validity of the PCQ in a time frame
of 1-12 months after a false-positive screening mammography.3 Because we
had to make major changes to the PCQ, we developed a new questionnaire:
Consequences Of Screening in Breast Cancer (COS-BC).(3) We have validated
the COS-BC using the Rasch Item Response Theory model and found that the
measure is a reliable multi-dimensional instrument for short- and long-
term psychosocial consequences of false-positive screening
mammography.(4;5) Therefore, it is unfortunate that Bond and colleagues do
not discuss the inadequacy of the psychological measures included in their
systematic review, and that a valid and reliable self-reported outcome
measure with high content validity does exist. The inadequacy of the
generic measures included in Bond et al's review could also be a plausible
explanation as to why they found that: "Heterogeneity was such that meta-
analysis was not possible".
It is also difficult to understand why Bond and colleagues have
limited their review only to include trials conducted in the UK. Why
should we expect different psychological reactions to a false-positive
screening mammography in different countries? The COS-BC has been
translated, adapted, and tested for relevance in a Swedish context, and we
found essentially no differences in psychosocial consequences of false-
positive screening mammography in Denmark and Sweden.(6) Together with
other colleagues, I have conducted the same translation, adaptation, and
test of relevance of the COS-BC in Norway, the Netherlands, and Germany,
with the same result as in Sweden (these projects are in progress).
The second outcome of Bond and colleagues is attendance to the next
screening round after a false-positive mammography. In some countries,
researchers have found that these women have a higher attendance to the
next screening round than those with a normal screening result. In other
countries, researchers have found the opposite, or similar attendance
rates. In my qualitative single- and focus group-interviews, some women
said that they did not dare to go to next screening after all they had
experienced after a false-positive result.(4) Others said they did not
dare to stay away.(4) If the psychological impact of a false-positive
screening mammography can be ambivalent feelings about attendance to the
next screening round, re-attendance is a poor surrogate outcome for the
psychological impact of a false-positive screening mammography.
References
(1) Bond M, Pavey T, Welch K, et al.
Psychological consequences of false-positive screening mammograms in the
UK. Evid Based Med 2012.
(2) Brodersen J, Thorsen H, Cockburn J. The adequacy of measurement
of short and long-term consequences of false-positive screening
mammography. J Med Screen 2004;11(1):39-44.
(3) Brodersen J, Thorsen H. Consequences Of Screening in Breast
Cancer (COS-BC): development of a questionnaire. Scand J Prim Health Care
2008; 26(4):251-256.
(4) Brodersen J. Measuring psychosocial consequences of false-
positive screening results - breast cancer as an example. Department of
General Practice, Institute of Public Health, Faculty of Health Sciences,
University of Copenhagen: M?nedsskrift for Praktisk L?gegerning,
Copenhagen. ISBN: 87-88638-36-7; 2006.
(5) Brodersen J, Thorsen H, Kreiner S. Validation of a condition-
specific measure for women having an abnormal screening mammography. Value
in Health 2007;10(4):294-304.
(6) Bolejko A, Wann-Hansson C, Zackrisson S, et al.
Adaptation to Swedish and further development of the 'Consequences of
Screening - Breast Cancer' questionnaire: a multimethod study. Scand J
Caring Sci 2012.
Dear Editor, The trial has two arms: magsulf and placebo. In my opinion the
subjects should give informed consent and instead of blinding the
treatment, the subjects should be able to opt for which arm they would
like to participate. And lastly, instead of placebo some other treatment
like diazepam or phenytoin should have been given as denying treatment is
unethical. Moreover, the magsulf has severe side effects e.g. res...
Dear Editor, The trial has two arms: magsulf and placebo. In my opinion the
subjects should give informed consent and instead of blinding the
treatment, the subjects should be able to opt for which arm they would
like to participate. And lastly, instead of placebo some other treatment
like diazepam or phenytoin should have been given as denying treatment is
unethical. Moreover, the magsulf has severe side effects e.g. respiratory
rate goes down. Because of low therapeutic index, it has to be given
cautiously.
We thank Beverly Winikoff and Jill Durocher for their thoughtful
commentary.(1) Winikoff and Durocher note that the incidence of PPH in
our study's (2) oxytocin group was higher than expected. This deviance
can occur, particularly in studies with relatively small samples such as
ours. Regardless, the randomization produced study groups with similar
characteristics to each other,(2) although this par...
We thank Beverly Winikoff and Jill Durocher for their thoughtful
commentary.(1) Winikoff and Durocher note that the incidence of PPH in
our study's (2) oxytocin group was higher than expected. This deviance
can occur, particularly in studies with relatively small samples such as
ours. Regardless, the randomization produced study groups with similar
characteristics to each other,(2) although this particular sample of women
had higher risk of postpartum hemorrhage than the general population,
something that might be expected in the study hospital, a referral center.
Our results were also consistent with a previously published study
comparing sublingual administration of 400 mg tablet misoprostol with
oxytocin, one among various criteria upon which causal associations are
judged to exist that our study met.(3) We agree and question the
pragmatism of a powdered formulation in the article.(2) The potential to
reduce drug costs by 33% remains substantial for a medication that is
widely recommended for PPH prevention.(4)
We think there is little basis to question the drug potency in our
study. The drug manufacturer, Astra-Zeneca provided us with the study
medication directly, and we assume the potency was acceptable to the
manufacturer upon distribution. Unlike the oxytocin stored under variable
field conditions, potentially exposed to sunlight and high temperatures
(potentially without refrigeration prior to their purchase in the cited
Ghana study),(5) the packaged study medications were stored in a
refrigerator maintained at 2 to 8 degrees Celsius within the clinical
pharmacy department at our hospital until their use as stated in the
manuscript.(2) What is not well known is whether intramuscular
administration of oxytocin is less efficacious than oxytocin administered
in intravenous solution; the Cochrane Review of uterotonics for PPH
prevention typically analyzed IM and IV administration jointly(6) and
whether the strong observed effect is attributable to the powdered
formulation.
We agree that further investigation of these issues will clarify the
questions our article raises about sublingual administration of lower dose
misoprostol for PPH prevention.
References
1. Winikoff B, Durocher J. Postpartum bleeding is reduced with sublingual
powdered misoprostol when compared with oxytocin injection, but a new
formulation of misoprostol is unlikely to revolutionise postpartum
haemorrhage care. Evid Based Med. 2012 Nov 2. 10.1136/eb-2012-100966.
2. Bellad M, Tara D, Ganachari M, et al. Prevention of postpartum
haemorrhage with sublingual misoprostol or oxytocin: a double-blind
randomised controlled trial. BJOG 2012;119:975-86.
3. Rothman KJ. What is Causation?" in Epidemiology: An Introduction.
Oxford University Press, New York. 2012;pp 33
4. WHO recommendations for the prevention and treatment of postpartum
haemorrhage 2012
http://apps.who.int/iris/bitstream/10665/75411/1/9789241548502_eng.pdf
5. Stanton C, Koski A, Cofie P, et al. Uterotonic drug quality: an
assessment of the potency of injectable uterotonic drugs purchased by
simulated clients in three districts in Ghana. BMJ Open 2012;2:e000431.
6. Gülmezoglu AM, Forna F, Villar J, Hofmeyr GJ. Prostaglandins for
preventing postpartum haemorrhage. Cochrane Database of Systematic Reviews
2007, Issue 3. Art. No.: CD000494. DOI: 10.1002/14651858.CD000494.pub3.
Medication incidents are the commonest reported clinical incident in
children and the second most common in neonates. [1] Current evidence is
that the most effective method of reducing these incidents in the acute
hospital is to have frequent attendance on the ward by a clinical
pharmacist. [2,3] This was discussed by Chua in Evidence Based
Medicine.[4]
Medication incidents are the commonest reported clinical incident in
children and the second most common in neonates. [1] Current evidence is
that the most effective method of reducing these incidents in the acute
hospital is to have frequent attendance on the ward by a clinical
pharmacist. [2,3] This was discussed by Chua in Evidence Based
Medicine.[4]
We wanted to see how many other units in Northern and Cumbria Regions
of England were in a similar situation. A member of staff from each of
eleven children's ward and neonatal units in the Northern Region of
England was telephoned. (Great North Children's Hospital, Sunderland Royal
Hospital, James Cook University Hospital, North Tyneside General Hospital,
Carlisle Royal Infirmary, West Cumberland Hospital, South Tyneside General
Hospital, Queen Elizabeth Hospital Gateshead, North Tees General Hospital
and the two inpatient units in our Trust: University Hospital North Durham
and Darlington Memorial Hospital). If they had a pharmacist visit three
times a week or more to review inpatient and discharge drugs in real time
they were scored as having ward based pharmacists. Weekly visits to
provide a ward top-up service were not counted.
Of the eleven neonatal units, five (45%) had clinical pharmacists. Of
the eleven inpatient children's wards, five (45%) had clinical
pharmacists. These five units were not the same for neonates and
paediatrics.
CDDFT is about to pilot a clinical pharmacist to support the
paediatric and neonatal patients within the Trust. We wonder if this issue
has been identified in other units and if so whether there are examples of
innovative practice and outcome measures that address this?
References
1) National Patient Safety Agency. Review of patient safety for
children and young people.
2) Sanghera N, Chan P-Y, Khaki ZF et al. Interventions of Hospital
Pharmacists in Improving Drug Therapy in Children. A systematic Literature
Review. Drug Safety 2006 (11): 1031-1047
3) McCartney RJ, McCartney RG, Postle JA et al. An Evaluation of
Clinical Pharmacist Contributions in Paediatrics Arch Dis Child 2011 96:e1
4) Chua SS. Errors detected in 19% of paediatric medication
preparations and administrations across five hospitals in London. Evid
Based Med 2010;15:123-124 doi:10.1136/ebm1087
We would like to thank DeFrank and Brewer for their interest in our
recently published paper: Long-Term Psychosocial Consequences of False-
Positive Screening Mammography.(1)
In the Methods section DeFrank and Brewer write: "Brodersen and
colleagues conducted a study of 454 adult women in Denmark screened in the
same time period who had normal mammography screening results, false-
positives or...
We would like to thank DeFrank and Brewer for their interest in our
recently published paper: Long-Term Psychosocial Consequences of False-
Positive Screening Mammography.(1)
In the Methods section DeFrank and Brewer write: "Brodersen and
colleagues conducted a study of 454 adult women in Denmark screened in the
same time period who had normal mammography screening results, false-
positives or breast cancer diagnoses." We (Brodersen & Siersma)
included 454 adult women in Denmark who had abnormal mammography screening
results (false-positives or breast cancer diagnoses) and 864 women with
normal screening results - all 1318 screened in the same time period.
In the Methods section DeFrank and Brewer also state that the
questionnaire we used: the Consequences Of Screening in Breast Cancer (COS
-BC), is a revised version of the question: the Psychosocial Consequences
Questionnaire (PCQ). This is not the case. Together with the developer of
the original Australian version of the PCQ - deceased Professor Jill
Cockburn - we published a systematic reviewed on "The adequacy of
measurement of short and long-term consequences of false-positive
screening mammography".(2) Part of our conclusion was: "The PCQ is an
adequate questionnaire for measuring short-term consequences, and the PCQ
is preferable to other measures because of its higher sensitivity.
However, there is little evidence that the PCQ is able to adequately
detect all long-term consequences of screening mammography. Given the
inadequacy of the measurement instruments used, any current conclusions
about the long-term consequences of false-positive results of screening
mammography must remain tentative".
In a qualitative study including six focus interviews with women having
false-positive screening mammography we found that the PCQ includes
ambiguous items, does not cover all psychosocial consequences of false-
positive screening mammography and three items from the PCQ were deleted
because they were judged by interviewees to be irrelevant.(3) We also
found that the women's experiences in the critical period from abnormal
screening mammography until final false-positive diagnosis differed
entirely from their experiences after the final diagnosis.(3) Therefore,
fifteen new items were generated to cover the negative psychosocial
consequences of abnormal and false-positive screening mammography
comprehensively.(3) Five new items were produced that concerned the
consequences of screening mammography during the period after being
declared ''free from'' suspicion of cancer.(3) Response options for the
positive items were changed to allow responses in both positive and
negative directions. Our conclusion was: "Because of the major changes to
both parts of the PCQ the measure derived from this study should be
regarded as a new questionnaire with two parts: Consequences Of Screening
in Breast Cancer (COS-BC). Part II focuses on the long-term consequences
of a false-positive screening mammography".(3)
Because we had developed a new questionnaire (based on Jill Cockburn's
work) we conducted two psychometric studies using the Item Response Theory
Partial Credit Rasch model for polytomous items plus Classical Test Theory
to validate the COS-BC.(4;5) Therefore, it is slightly confusing that
DeFrank and Brewer calls COS-BC for PCQr when it actually is a new
measure.
Due to this extensive qualitative and statistical psychometrical work we
have provided robust high quality evidence that the subscales of the COS-
BC measure each distinct constructs that are unidimensional. It is
therefore wrong when DeFrank and Brewer in the Commentary section write
that some "subscales mix multiple constructs". Furthermore, we have
revealed that the PCQ lacks content validity and encompass ambiguous
items. Because the COS-BC has high content validity and adequate
psychometric properties we can conclude that the COS-BC and the PCQ do not
measure the same thing. It is therefore not appropriate that DeFrank and
Brewer compare the scores of the PCQ with the scores of the COS-BC.
Furthermore, standard methods, like the correlation coefficients are
different from our linear regression methods, and do not adjust for the
differential dropout. As stated in our method section: "We used
generalized estimating equations methods to account for repeated
measurement on the same individual. To adjust for possible bias resulting
from differential dropout from the study, the scores available at each
follow-up time point were weighted by the inverse of an estimate of the
probability of this score being observed at that time point".(1) Those
people that are worse off have the tendency to drop out in surveys. In our
case, women diagnosed with breast cancer and the women that are most
affected by the false-positive screening result could have a higher
tendency to drop out; analysing only the subjects that did not drop out
will then artificially decrease effects. By using inverse probability
weighing and correcting the confidence intervals accordingly using
generalized estimating equations we have adjusted for this differential
drop out. The relatively small effect sizes found and commented on by
DeFrank and Brewer using our data may well be an artefact of not adjusting
for dropout.
In the Commentary section DeFrank and Brewer also write that the COS
-BC "has a subscale for breast self-examination, a behaviour that many
guidelines now recommended against". However, the subscale has not
anything to do with breast self-examination recommendations. In our
qualitative study we found that women with false-positive screening
mammography examined their breasts with their hands and examined their
breasts in a mirror as a psychosocial consequence of the false-positive
results and not because of any recommendation.
In the Commentary section DeFrank and Brewer also write: "The second
half of the PCQr assesses how patients...". Most of these women are not
patients. The main part of the women in our survey had a normal or a false
-positive screening result and besides that they were healthy. In the same
sentence DeFrank and Brewer continue:"....think the testing affected them
and uses an uncommon scoring system." We do not find the scoring system as
a limitation since the response categories and scoring system for part 2
of the COS-BC were developed during the previous mentioned focus group
interviews.(3) Furthermore, part2 of the COS-BC was validated using the
empirical knowledge from these interviews,(3) the theory of cognitive
dissonance, the theory of sense of coherence, and as mentioned above Item
Response Theory Partial Credit Rasch model for polytomous items. (4;6)
In the Commentary section DeFrank and Brewer lastly write: "Finally,
the absence of analyses that demonstrate whether changes over time
differed by test results, the internal consistency of measures and their
reliability over time. Study findings would be strengthened by the
inclusion of outcomes assessed before screening or learning of test
results." Test for interaction between time and the three screening groups
could have been added to the tables, but such test may not have been very
informative because of the large differences between the trajectories in
the start of follow-up: most tests for interaction were highly
significant. Where items are shown to fit a Rasch model the measure can be
shown to posses criterion-related construct validity,(7) to be objective
(invariant),(8) sufficient(9) and, therefore, also reliable.(10)
Furthermore, we have provided evidence that the items in the subscales do
not posses differential item functioning in relation to time.
References
(1) Brodersen J, Siersma VD. Long-Term Psychosocial Consequences of
False-Positive Screening Mammography. The Annals of Family Medicine 2013;11(2):106-15.
(2) Brodersen J, Thorsen H, Cockburn J. The adequacy of measurement
of short and long-term consequences of false-positive screening
mammography. J Med Screen 2004 Mar 1;11(1):39-44.
(3) Brodersen J, Thorsen H. Consequences Of Screening in Breast
Cancer (COS-BC): development of a questionnaire. Scand J Prim Health Care
20081;26(4):251-6.
(4) Brodersen J. Measuring psychosocial consequences of false-
positive screening results - breast cancer as an example. Department of
General Practice, Institute of Public Health, Faculty of Health Sciences,
University of Copenhagen: M?nedsskrift for Praktisk L?gegerning,
Copenhagen. ISBN: 87-88638-36-7; 2006.
(5) Brodersen J, Thorsen H, Kreiner S. Validation of a condition-
specific measure for women having an abnormal screening mammography. Value
in Health 2007;10(4):294-304.
(6) Brodersen J, Thorsen H, Kreiner S. Consequences Of Screening in
Lung Cancer: Development and Dimensionality of a Questionnaire. Value in
Health 2010;13(5):601-12.
(7) Rosenbaum PR. Criterion-related construct validity. Psychometrika
1989 ;54(4):625-33.
(8) Rasch G. An Informal Report on a Theory of Objectivity in
Comparisons. In: Van der Kamp LJTh, Vlek CAJ, editors. Psychological
Measurement Theory.Leyden: University of Leyden; 1967:1-19.
Montori and Brito draw attention to the limited clinical significance
of statins' raising glucose (1), consistent with the non-linear
association of fasting glucose with cardiovascular disease (2). It is
quite possible that the limited clinical significance of statins' minor
effects on glucose also translates into limited aetiological significance.
On the other hand, statins are not alone in having diver...
Montori and Brito draw attention to the limited clinical significance
of statins' raising glucose (1), consistent with the non-linear
association of fasting glucose with cardiovascular disease (2). It is
quite possible that the limited clinical significance of statins' minor
effects on glucose also translates into limited aetiological significance.
On the other hand, statins are not alone in having divergent effects on
diabetes and cardiovascular disease. At least one other well-established
therapy for preventing cardiovascular disease also has the same set of
effects. Diuretics similarly both decrease the risk of cardiovascular
disease but also increase the risk of diabetes. Conversely, some effective
treatments for diabetes have been found to increase the risk of
cardiovascular disease, such as rosiglitazone and sulphonureas.
Notwithstanding, the very well-established relation between diabetes and
cardiovascular disease, this consistent pattern from experimental evidence
suggests the existence of an underlying exposure which may both protect
against cardiovascular disease and cause diabetes.
In randomized controlled trials testosterone therapy improves glucose
metabolism (3) but increases the risk of cardiovascular-related events
(4). Moreover, evidence from randomized controlled trials shows that
statins reduce testosterone (5). Taking all this experimental evidence
together raises the possibility that the mechanism underlying the
divergent effects of statins on both diabetes and cardiovascular disease
could be androgen modulation. Whether such a mechanism could also be
relevant to the other therapies which also have divergent effects on
diabetes and cardiovascular disease has never been considered. Notably
spironolactone, which is known to decrease androgens, also has divergent
effects on cardiovascular disease and diabetes, preventing mortality in
heart failure but adversely affecting glucose metabolism (6). A small
mechanistic randomized controlled trial examining whether the effects of
statins on key factors in the ischemic pathway, such as markers of
endothelial function or clotting factors (7), could be mediated by
androgens, would provide confirmation or refutation. Androgen modulation
as a contributor to the mechanism of statins, and perhaps other therapies,
not only potentially provides a unified explanation for paradoxical
results from randomized controlled trials, but also is consistent with the
higher age-standardized rates of cardiovascular disease among men than
women.
References
(1) Montori VM, Brito JP. Statins induce hyperglycaemia of uncertain
importance. Evid Based Med 2013;18(4):157-158.
(2) Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di AE et al.
Diabetes mellitus, fasting blood glucose concentration, and risk of
vascular disease: a collaborative meta-analysis of 102 prospective
studies. Lancet 2010;375(9733):2215-2222.
(3) Jones TH, Arver S, Behre HM, Buvat J, Meuleman E, Moncada I et al.
Testosterone replacement in hypogonadal men with type 2 diabetes and/or
metabolic syndrome (the TIMES2 study). Diabetes Care 2011;34(4):828-837.
(4) Xu L, Freeman G, Cowling BJ, Schooling CM. Testosterone therapy and
cardiovascular events among men: a systematic review and meta-analysis of
placebo-controlled randomized trials. BMC Med 2013;11:108.
(5) Schooling CM, Au Yeung SL, Freeman G, Cowling B.J. The effect of
statins on testosterone in men and women: a systematic review and meta-
analysis of randomized controlled trials. BMC Medicine 2013;11:57.
(6) Swaminathan K, Davies J, George J, Rajendra NS, Morris AD, Struthers
AD. Spironolactone for poorly controlled hypertension in type 2 diabetes:
conflicting effects on blood pressure, endothelial function, glycaemic
control and hormonal profiles. Diabetologia 2008;51(5):762-768.
(7) Violi F, Calvieri C, Ferro D, Pignatelli P. Statins as antithrombotic
drugs. Circulation 2013; 127(2):251-257.
We are very grateful for the positive comments from Dr Basaria
about our meta-analysis of randomized controlled trials (RCTs) showing
that testosterone therapy among men increases the risk of a cardiovascular
-related event (1;2). As per the Preferred Reporting Items for Systematic
Reviews and meta-Analysis (PRISMA) guidelines (item 25) (3), we also
highlighted the limitations of our review. We are surpr...
We are very grateful for the positive comments from Dr Basaria
about our meta-analysis of randomized controlled trials (RCTs) showing
that testosterone therapy among men increases the risk of a cardiovascular
-related event (1;2). As per the Preferred Reporting Items for Systematic
Reviews and meta-Analysis (PRISMA) guidelines (item 25) (3), we also
highlighted the limitations of our review. We are surprised that a comment
on compliance with the PRISMA guidelines is followed by the sentence
"Therefore, firm conclusions regarding the association between
testosterone therapy and CVD cannot be drawn from this study" (1). This
line of reasoning would preclude firm conclusions
being drawn from all well-conducted meta-analyses of RCTs, which
inevitably each have limitations as well as strengths. In a recent update of the Competing Interests statement associated with
his commentary, Dr Basaria, and the editor, have clarified a number of
potential conflicts of interest including connections with pharmaceutical
companies selling or developing testosterone therapy, which may affect
readers' interpretation of the commentary. A separate report describes the
way pharmaceutical companies have subtly promoted testosterone therapy (4)
despite growing evidence of its harmful effects.
References
(1) Basaria S. Need for standardising adverse event reporting
in testosterone
trials. Evid Based Med 2013.
(2) Xu L, Freeman G, Cowling BJ, et al. Testosterone
and cardiovascular events among men: a systematic review and meta-analysis
of placebo-controlled randomized trials. BMC Med 2013;11(1):108.
(3) Moher D, Liberati A, Tetzlaff J, et al. Preferred
reporting items for systematic reviews and meta-analyses: the PRISMA
statement. PLoS Med 2009;6(7):e1000097.
(4) Braun SR. Promoting "Low T": A Medical Writer's
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Disclosure of conflicts of interest in Japanese randomized controlled trials
Dear Editor,
Disclosure of potential conflicts of interest (COI) is essential in interpreting randomized controlled trials with less risk of bias. In 2008, the Japanese Ministry of Health, Labour and Welfare issued an ethical guideline for clinical research that endorsed disclosure of potential COI 1. To assess impact of the gu...
Dear Editor,
One third of patients who undergo surgery will experience postoperative nausea and vomiting (PONV) which can be very distressing (wound dehiscences and pulmonary complications)[1]. Rawlinson and colleagues [2] have made an excellent systematic review of randomised controlled trials, whose conclusions included the confirmation of intravenous dexamethasone and ondansetron (5-HT3 antagonist) as effective...
Dear Editor,
In this week's EBM, Bond and colleagues report a systematic review entitled: 'Psychological consequences of false-positive screening mammograms in the UK'.(1) Their two main outcomes are self-reported questionnaires, and attendance at the next screening round.
Together with two colleagues, I conducted a systematic review in 2004 on the adequacy of measurement of short and long-term consequence...
Dear Editor, The trial has two arms: magsulf and placebo. In my opinion the subjects should give informed consent and instead of blinding the treatment, the subjects should be able to opt for which arm they would like to participate. And lastly, instead of placebo some other treatment like diazepam or phenytoin should have been given as denying treatment is unethical. Moreover, the magsulf has severe side effects e.g. res...
Dear Editor,
We thank Beverly Winikoff and Jill Durocher for their thoughtful commentary.(1) Winikoff and Durocher note that the incidence of PPH in our study's (2) oxytocin group was higher than expected. This deviance can occur, particularly in studies with relatively small samples such as ours. Regardless, the randomization produced study groups with similar characteristics to each other,(2) although this par...
Dear Editor,
Medication incidents are the commonest reported clinical incident in children and the second most common in neonates. [1] Current evidence is that the most effective method of reducing these incidents in the acute hospital is to have frequent attendance on the ward by a clinical pharmacist. [2,3] This was discussed by Chua in Evidence Based Medicine.[4]
We wanted to see how many other units i...
Dear Editor,
We would like to thank DeFrank and Brewer for their interest in our recently published paper: Long-Term Psychosocial Consequences of False- Positive Screening Mammography.(1)
In the Methods section DeFrank and Brewer write: "Brodersen and colleagues conducted a study of 454 adult women in Denmark screened in the same time period who had normal mammography screening results, false- positives or...
Dear Editor,
Montori and Brito draw attention to the limited clinical significance of statins' raising glucose (1), consistent with the non-linear association of fasting glucose with cardiovascular disease (2). It is quite possible that the limited clinical significance of statins' minor effects on glucose also translates into limited aetiological significance. On the other hand, statins are not alone in having diver...
Dear Editor,
We are very grateful for the positive comments from Dr Basaria about our meta-analysis of randomized controlled trials (RCTs) showing that testosterone therapy among men increases the risk of a cardiovascular -related event (1;2). As per the Preferred Reporting Items for Systematic Reviews and meta-Analysis (PRISMA) guidelines (item 25) (3), we also highlighted the limitations of our review. We are surpr...
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