Regarding the potential usefulness of appropriate labels:
The beginning of wisdom is to call things by their right names. Madame
James M. Walker, MD, FACP
Chief Health Information Officer
Geisinger Health System
...it's all very well planning what you will do in six months, what you
will do in a year, but it's no good at all if you don't have a plan for
Hilary Mantel. Wolf Hall.
>>> Rod Jackson <[log in to unmask]> 6/8/2010 12:03 AM >>>
Hi David - no label is perfect but often they can be helpful. While
concept of experimental vs observational studies are ¼slippery* as you
mention, they are part of the ¼complete and clear textual description*
you indicate is important.
However as I suggest at the end of Steve*s description of the studies,
key issue for Steve to consider is whether there is an appropriate
On 7/06/10 2:32 AM, "Braunholtz, David A." <[log in to unmask]>
> The concept of experimental vs observational study can be quite
> not particularly helpful, it seems to me.
> Eg following Rod's definitions, a study of an intervention for the
> population (comparing before / after) could be experimental, or
> depending on whether the 'investigator' is (or isn't) also the one
> taking the administrative decision to introduce the intervention. ie
> exact same data could be labelled experimental, or observational -
> making the label irrelevant, in this case, to any assessment of
> the data for drawing inferences ?!
> More important than labels, I think, is a complete & clear textual
> of what is being compared with what (systematic reviewers really
> this !) , and a thorough appreciation of the factors, apart from the
> the intervention / exposure, which may be causing any differences
> [log in to unmask]
> University of Aberdeen
> From: Evidence based health (EBH)
[[log in to unmask]] On
> Behalf Of Rod Jackson [[log in to unmask]]
> Sent: 06 June 2010 10:45
> To: [log in to unmask]
> Subject: Re: Observational studies
> Hi Steve - I have commented on the classification of each of the
> the end of each of your descriptions.
> However as an introduction, epidemiological studies can be classified
> several ways.
> First, studies can be classified as either experimental or
> an experiment, the study investigator controls the allocation of the
> (or exposures) of interest to the participants. In an experiment the
> is always an ¼intervention* which is usually compared with another
> intervention or placebo. As you know, in the ideal experiment,
> interventions to different arms of the study is done using a
> process so each participant has an equal chance of being in any of
> arms (i.e. a rct). The other type of study is an observational study
> the investigator 'observes' (rather than controls) what each
> exposed to. For example the investigator observes whether the
> taking a particular drug or not or, say, whether they are smokers or
> smokers. The participants are then allocated to different arms of the
> based on their exposure status.
> Second, studies are then classified by whether the participants are
> up over time to determine the study outcomes (a follow-up or
> study) or whether whether both exposure status and outcome status is
> at the same time (a cross-sectional study). All experiments are
> because if the experimenters allocate participants to exposure, they
> follow them for a period of time to determine the effect of the
> outcomes (unless the effect of the exposure on outcomes is
> is theoretically possible but unlikely). In contrast observational
> be longitudinal (i.e. Cohort studies) or cross-sectional (e.g.
Surveys) or a
> combination of both. Observational studies can be both longitudinal
> cross-section because the investigator only observes if participants
> exposed to the exposure of interest. Therefore participants have
> been exposed (or not exposed) to the exposure of interest for some
> the study starts.
> Third, most studies have at least 2 arms - exposure and comparison
> but both experiments and observational studies could just have one
> no comparison arm). Small groups of patients in ¼one arm* studies
> typically called case series. They are experiments if the
> controls the ¼exposure* and observational studies if the exposure
> is not part of a study and the investigator observes what
> been exposed to. However even most small case series can be divided
> smaller subgroups (as in some of the studies you describe) so the
> of a case series is rather lose but generally describes one smallish
> patients with a similar condition and similar treatment who are
followed for a
> period of time.
> While a cohort study classification is generally only given to
> observational studies, RCTs could be considered as cohort studies in
> exposure has been randomly allocated by the investigator.
> A case-control study is a sub-type of a observational cohort study.
> have heard about nested case-control studies. The standard case
> is simply nested in a virtual cohort study. None of your studies are
> control studies.
> I hope these comments are of some help
> Rod Jackson
> Professor of Epidemiology
> Section of Epidemiology and Biostatistics
> School of Population Health, Tamaki Campus
> Faculty of Medical & Health Sciences, University of Auckland
> Private Bag 92019
> Auckland, New Zealand
> On 6/06/10 8:38 AM, "Steve Mathieu" <[log in to unmask]>
>> > I would be really grateful for some help with categorising some
>> > types of observational studies. I have included some example
>> > 1) 12 patients with the need for inotropic support were studied.
>> > levosimendan (12.5 mg) was administered at a rate of 0.1-0.2
>> > kg(-1).min(-1), either alone or in addition to pre-existing
>> > Haemodynamic measurements were obtained at baseline, and at 3 h, 6
h, 12 h,
>> > and 24 h after the start of the levosimendan infusion.
>> > significantly increased cardiac output from (mean+/-SD)
>> > 5.2+/-1.51 min(-1) after 24h (P=0.013), by increases in stroke
>> > (baseline 47+/-15 ml, after 24h 57+/-25 ml, P=0.05), as heart rate
>> > unchanged. Systemic vascular resistance decreased from 1239+/-430
>> > dyn.sec.cm(-5) at baseline to 963+/-322 dyn.sec. cm(-5) at 24h
>> > Pre-existing inotropic therapy present in ten patients remained
>> > was reduced. In postoperative critically ill patients, infusion
>> > levosimendan exerted favourable haemodynamic responses.
>> > cardiac output by increasing stroke volume, which might be
>> > primarily to its inotropic properties. Due to its cyclic
>> > monophosphate independent positive inotropic effects, levosimendan
>> > value as adjunctive therapy to other inotropic drugs in critically
>> > patients'
>> > Is this therefore a cohort study (one arm levosimendan + other
>> > other arm = inotropes alone)? Prospective with 2 different
>> > albeit the patient groups are not matched other than all post op
>> > necessitating treatment for heat failure
> This could be described as a case series. It is an experiment as
> above. All patients were given levosimendan by the investigators and
> the patients were already on pre-existing therapy. The study is
> information was collected at the time of levosimendan administration
> patients were then followed over a period of time. This study could
> considered as a very small cohort study in the sense that all
> studies are cohort studies. Almost any cohort can be divided into
> 'arms' as is possible with this study so you could analyse it in
> 'arms.' However you would want to know why some patients received
> levosimendan while others didn*t. The reason may be a major cause of
>> > 2) This retrospective analysis covers our single centre
>> > July 2000 and December 2004, 41 consecutive patients were treated
>> > complication. Of these, 38 patients are included in this
>> > analysis as 3 patients died in the operating room. Levosimendan
>> > the treatment protocol for the last nine patients. RESULTS: Of 29
>> > treated without levosimendan, 20 could be weaned off the device, 9
>> > intensive care unit discharge, 7 left hospital alive and 3
>> > All 9 patients treated with levosimendan could be weaned, 8 were
>> > alive from ICU and hospital, and 7 lived 180 days after surgery (p
>> > 180 day survival). Plasma lactate after explantation of the device
>> > significantly lower (p = 0.002), as were epinephrine doses.
>> > Is this a case control study? Retrospective with 2 different
>> > (levosimendan + treatment protocol vs treatment protocol). Very
>> > in terms of numbers 29 vs 9
> This study is not an experiment because the investigators did not
> allocation of the exposure as part of a study. Instead they observed
> the event. The study is described as retrospective as it was
> the study period had in effect finished. However as information on
> (i.e. interventions) was documented in records at the time they were
> as this was done before the outcomes (which were also documented in
> this is actually an analysis based on prospectively collected data.
> different from a retrospective study in which the data wasn*t well
> at the time of exposure or outcome and the data has to be collected
> retrospectively rather than retrospectively extracted from
> records. This study could be considered a case series but it could
> considered as a cohort study with two arms. The key potential cause
> related to the two groups being followed over different time periods
> the severity of disease and background treatment may differ in the
>> > 3) The Brazilian Evaluation of Levosimendan Infusion Efficacy
>> > was prospective, multicenter, observational and included 182
>> > patients, all of which received open-label levosimendan. Primary
>> > hospital discharge without additional inotropic therapy
>> > end points were changes in hemodynamics, clinical parameters, and
>> > natriuretic peptide (BNP). RESULTS: Mortality rate was 14.8%, and
139 of >>
>> > patients were responders. In non responders it was 62.8%. Systolic
>> > pressure was a predictor of response. In b-adrenergic agonist
>> > 55.8% were responders. Overall, 54 patients experienced at least
>> > event; most of them resolved either spontaneously or after
>> > reduction. A significant improvement in quality of life was
verified at 2-6
>> > months of follow-up (p<0.0001). CONCLUSION: Our results suggest
>> > infusion as an alternative therapy in the short term management of
>> > patients. HF severity can influence the response to levosimendan
>> > Prospective studies are warranted in a Brazilian cohort including
>> > disease.
>> > This has been recorded in the journal as 'prospective,
>> > observational' and later 'open-label and non randomised'. There is
>> > comparator group identified at the start i.e the control group who
>> > receive treatment. However, they have found during the analysis
>> > patients 'respond' and others are 'non responders' to treatment
>> > levosimendan. Does this now become a cohort study because of
>> > statistical analyses of these groups, or is it a (very extensive)
> This study has some features of the two previous studies. If the
> were responsible for giving the participants the infusion, then it is
> randomised experiment with two groups, one receiving only
> the other receiving levosimendan plus additional inotropic therapy.
> prospective so could be considered a cohort study if the
investigators did not
> control the intervention. It could also be considered as an extensive
> series as you suggest.
>> > 4) Twenty-six (21 male) consecutive patients were studied,
>> > levosimendan administrations (bolus + 24h infusion), aged
>> > with decompensated chronic heart failure, in NYHA functional class
>> > (78.1% in class IV), and cardiac index (CI) <2.5 l/min/m2.
>> > class), non-invasive hemodynamic (echocardiography) and
>> > ECLIA NT-ProBNP) evaluations were performed before levosimendan
>> > and on days 1, 4, 10 and 30. RESULTS: 1) Until day 10, there was
>> > decrease in NT-ProBNP values and weight (p<0.001), with an
increase in CI
>> > (p<0.001); 2) NYHA functional class improved progressively, with
76% of the
>> > patients in NYHA class II at day 30; 3) NT-ProBNP values at day 1
>> > inversely (r=-0.414; p=0.024) with CI at day 4; and 4) the
>> > in NT-ProBNP values at day 4 (relative to baseline values)
>> > weight loss at day 4 (r=0.495, p=0.005), day 10 (r=0.424, p=0.031)
>> > (r=0.486, p=0.030). CONCLUSION: Levosimendan therapy in patients
>> > decompensated chronic heart failure contributes to progressive
>> > improvement. The variations seen in NYHA class and hemodynamics
>> > in changes in NT-ProBNP.
>> > This presumably is a case series? Does a consecutive case series
>> > (if agree it is indeed a case series) carry any more validiity
>> > single cases are grouped together over a wider period?
> This is the most typical case series as there appears to be no
> The usefulness of these studies depends on your question. If it it
> along the lines of: ¼is levosimendan alone, or in addition to other
> more effective than other therapies alone in reducing morbidity and
> then these studies all suffer from the same fundamental flaw - there
> appropriate comparison group. You own retrospective analyses (study
> probably comes closest to having a meaningful comparison group, if
> reason the previous patients did not receive levosimendan was because
> unavailable. But not only are the numbers very small but the two
> from different time periods.
>> > Thank you very much in advance for your help with this. I'm afraid
>> > new to data analyses and whilst I have done some background
>> > to be baffled with some of the wording/categories when trying to
>> > appraise papers.
>> > Best wishes
>> > Steve
> The University of Aberdeen is a charity registered in Scotland, No
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