title: Basic statistics for clinicians: 3. Assessing the effects of treatment: measures of association. Interventional neurophysiology for pain control: duration of pain relief following repetitive transcranial magnetic stimulation of the motor cortex Intravenous Subhypnotic Propofol in Central Pain: A Double-Blind, Placebo-Controlled, Crossover Study Number needed to treat: easily understood and intuitively meaningful? Theoretical considerations and a randomized trial. Motor cortex rTMS restores defective intracortical inhibition in chronic neuropathic pain Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale The minimum clinically significant difference in visual analogue scale pain score does not differ with severity of pain Measured enthusiasm: does the method of reporting trial results alter perceptions of therapeutic effectiveness? Completeness of reporting trial results: effect on physicians' willingness to prescribe Danish GPs' perception of disease risk and benefit of prevention. Feeling good rather than feeling better matters more to patients. Clinical trials and clinical practice: do doctors use the same criteria to judge outcome?
abstract: In the third of a series of four articles the authors show the calculation of measures of association and discuss their usefulness in clinical decision making . From the rates of death or other " events " in experimental and control groups in a clinical trial , we can calculate the relative risk ( RR ) of the event after the experimental treatment , expressed as a percentage of the risk without such treatment . The absolute risk reduction ( ARR ) is the difference in the risk of an event between the groups . The relative risk reduction is the percentage of the baseline risk ( the risk of an event in the control patients ) removed as a result of therapy . The odds ratio ( OR ) , which is the measure of choice in case-control studies , gives the ratio of the odds of an event in the experimental group to those in the control group . The OR and the RR provide limited information in reporting the results of prospect i ve trials because they do not reflect changes in the baseline risk . The ARR and the number needed to treat , which tells the clinician how many patients need to be treated to prevent one event , reflect both the baseline risk and the relative risk reduction . If the timing of events is important -- to determine whether treatment extends life , for example -- survival curves are used to show when events occur over time The chronic electrical stimulation of a motor cortical area corresponding to a painful region of the body , by means of surgically-implanted epidural electrodes is a vali date d therapeutical strategy to control medication-resistant neurogenic pain . Repetitive transcranial magnetic stimulation ( rTMS ) permits to stimulate non-invasively and precisely the motor cortex . We applied a 20-min session of rTMS of the motor cortex at 10 Hz using a ' real ' or a ' sham ' coil in a series of 14 patients with intractable pain due to thalamic stroke or trigeminal neuropathy . We studied the effects of rTMS on pain level assessed on a 0 - 10 visual analogue scale from day 1 to day 12 following the rTMS session . A significant pain decrease was observed up to 8 days after the ' real ' rTMS session . This study shows that a transient pain relief can be induced in patients suffering from chronic neurogenic pain during about the week that follows a 20-min session of 10 Hz-rTMS applied over the motor cortex Objective To vali date IV subhypnotic propofol , a γ-aminobutyric acid A ( GABA-A ) agonist , as a diagnostic test for central pain . Methods The efficacy of systemic propofol ( 0.2 mg/kg IV bolus ) was evaluated in a double-blind , placebo-controlled and crossover fashion on both spontaneous ongoing pain and allodynia in 44 patients with chronic central pain of both brain and cord origin . Results Propofol was significantly superior to the placebo ( Intralipid , Kabi Pharmacia ) in reducing the intensity of spontaneous ongoing pain for up to 1 hour after the injection : 24 of 44 patients ( 55 % ) receiving propofol showed a significant reduction in spontaneous pain , whereas only 6 patients showed this after the placebo . Propofol also significantly reduced the intensity of both mechanical and cold allodynia . In a few cases , only the evoked components were abolished but not the spontaneous pain . In general , the side effects were minimal and consisted mainly of transitory burning upon injection of both propofol and placebo and slight lightheadedness in a few cases . Conclusions Systemic propofol induces analgesic effects on all studied components of central pain and highlights the key role of GABA modulation in central pain Graphic representation was used to explore to what extent the number needed to treat ( NNT ) conveys the appropriate notion of benefit for the individual patient in interventions aim ed at delaying adverse events . A sample of the Danish population ( n = 675 ) was interviewed face to face , and asked whether they would consent to a hypothetical drug that reduces the risk of heart attack . The benefit of the drug was expressed in terms of NNT and was r and omly set at 10 , 25 , 50 , 100 , 200 , and 400 . NNT does not convey information on the proportion of patients being helped by an intervention or the size of the delay of the adverse event intended to be prevented . The proportion of people consenting to the hypothetical drug was about 80 % , irrespective of NNT , and some of those who rejected the drug misinterpreted the meaning of NNT . Lay people may have difficulties in underst and ing the meaning of NNT , and clinicians may do well to use the NNT with caution until more is known about how patients comprehend it Objective : To assess cortical excitability changes in patients with chronic neuropathic pain at baseline and after repetitive transcranial magnetic stimulation ( rTMS ) of the motor cortex . Methods : In 22 patients with unilateral h and pain of various neurologic origins and 22 age-matched healthy controls , we studied the following parameters of cortical excitability : motor threshold at rest , motor evoked potential amplitude ratio at two intensities , cortical silent period ( CSP ) , and intracortical inhibition ( ICI ) and intracortical facilitation . We compared these parameters between healthy subjects and patients at baseline . We also studied excitability changes in the motor cortex corresponding to the painful h and of patients after active or sham rTMS of this cortical region at 1 or 10 Hz . Results : At baseline , CSP was shortened for the both hemispheres of patients vs healthy subjects , in correlation with pain score , while ICI was reduced only for the motor cortex corresponding to the painful h and . Regarding rTMS effects , the single significant change was ICI increase in the motor cortex corresponding to the painful h and , after active 10-Hz rTMS , in correlation with pain relief . Conclusion : Chronic neuropathic pain was associated with motor cortex disinhibition , suggesting impaired GABAergic neurotransmission related to some aspects of pain or to underlying sensory or motor disturbances . The analgesic effects produced by motor cortex stimulation could result , at least partly , from the restoration of defective intracortical inhibitory processes & NA ;  Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies Objective —To determine whether minimum clinical ly significant difference in visual analogue scale ( VAS ) pain score varies according to the severity of pain reported . Method — Prospect i ve descriptive study of adult patients in an urban emergency department ( ED ) . On presentation to the ED , patients marked the level of their pain on a 100 mm , non-hatched VAS scale . At 20 minute intervals thereafter they were asked to give a verbal categorical rating of their pain as “ a lot better ” , “ a little better ” , “ much the same ” , “ a little worse ” or “ much worse ” and to mark the level of pain on a VAS scale of the same type as used previously . It was pre-defined that patients with VAS pain scores of 30 mm or less would be categorised as having mild pain , those with scores of 70 mm or more were categorised as having severe pain and those from 31 mm to 69 mm , moderate pain . The minimal clinical ly significant difference ( MCSD ) in VAS pain score was defined as the mean difference between current and preceding scores when the subject reported “ a little worse ” or “ a little better ” pain . Results —156 patients were enrolled in the study , yielding 88 evaluable comparisons where pain was rated as “ a little better ” or “ a little worse ” . The MCSD in VAS score in the group overall was 12 mm ( 95%CI 9 mm to 15 mm ) . MCSD in VAS score for the “ mild pain ” group was 11 mm ( 95%CI 4 mm to 18 mm ) , for the “ moderate pain ” group 14 mm ( 95%CI 10 mm to 18 mm ) and for the severe pain group , 10 mm ( 95%CI 6 mm to 14 mm ) . There is no statistical difference between the MCSD in VAS score between the severity groups . Conclusions —The MCSD in VAS pain score does not differ with the severity of pain being experienced OBJECTIVE To compare clinicians ' ratings of therapeutic effectiveness when different trial end points were presented as percent reductions in relative compared with absolute risk and as numbers of patients treated to avoid one adverse outcome . DESIGN Survey , with r and om allocation of two question naires . SETTING Toronto teaching hospitals . RESPONDENTS Convenience sample of 100 faculty and housestaff in internal medicine and family medicine . INTERVENTION One question naire presented results for three end points of the Helsinki Heart Study as separate drug trials using only absolute differences in events ; the other showed the same end points as relative differences . Both question naires included a fourth " trial , " showing person-years of treatment needed to prevent one myocardial infa rct ion . MAIN OUTCOME MEASURE The " trials " were each rated on an 11-point scale , from treatment " harmful " to " very effective . " RESULTS Respondents ' ratings of effectiveness varied with the end point . Controlling for end point , ratings of effectiveness by the 50 participants receiving absolute event data were lower than those by 50 participants responding to relative risk reductions ( P < 0.001 ) ; however , no end-point difference was more than 0.6 scale points . For a " trial " reporting that 77 persons were treated for 5 years to prevent one myocardial infa rct ion , mean ratings were 2.3 or 1.8 scale points lower , respectively ( both P < 0.001 ) , than when the same data were shown as relative or absolute risk reductions . CONCLUSIONS Clinicians ' views of drug therapies are affected by the common use of relative risk reductions in both trial reports and advertisements , by end-point emphasis , and , above all , by underuse of summary measures that relate treatment burden to therapeutic yields in a clinical ly relevant manner Clinical trials may lead to conflicting results . We studied how different ways of reporting results affected physicians ' recommendations . A question naire distributed to 148 general practitioners presented results of a clinical trial where a reduction of cardiac events and an increase of mortality was reported . Results were shown in four different ways -- relative risk reduction , absolute risk reduction , percentages of event-free patients , number needing to be treated to prevent an event -- as if they derived from different trials . A fifth presentation was the reduced rate of cardiac events along with the increased rate of mortality .  Physicians were asked to estimate how much they would be willing to prescribe each drug . The mean agreement of physicians ' decisions was 77 (28)% for relative risk reduction , 24 (28)% for absolute risk reduction , 37 (37)% for different percentages event-free patients , 34 (34)% for number need to treat , and 23 (28)% for events reduction and mortality for increase ( p < 0.001 relative risk vs others ) . The method of reporting trial results and the completeness of information in the case of controversial results affects physicians willingness to prescribe BACKGROUND Uncertainty and risk are central issues in relation to health and health care services . Healthy individuals do not necessarily fall ill , despite the presence of risk factors . It has been documented that doctors , health service administrators and patients are more inclined to choose interventions against risk factors when information about the effects is presented in terms of relative risk reductions rather than absolute risk reductions . OBJECTIVES The objective of the study was to gain better insight into how GPs perceive risk of disease , and how this perception is influenced by the way the risk is presented , e.g. whether changes in risk are presented in absolute or relative terms . METHODS Question naires with clinical episodes were sent to 1500 Danish GPs . The GPs were r and omized into four groups of 375 , who all received the same case story with information about risk reduction achieved through medical treatment phrased in terms of either relative risk reduction , absolute risk reduction , number needed to treat or all of the aforementioned terms of risk reduction . The GPs were asked whether they would recommend medical treatment as primary prevention , knowing the case story and expected risk reduction . RESULTS The GPs ' attitude towards recommending medical treatment was dependent on the phrasing of risk reductions . Seventy-two per cent of doctors who received all information on risk reductions would definitely or probably recommend medication , while 91 % would recommend medication if information only about relative risk reduction was given , and 63 % would recommend medication if information was given in terms of absolute risk reduction or number needed to treat . CONCLUSION In order to advise patients in a rational way , in addition to knowledge of the patients ' preferences , doctors need to take into account all available measures of risk reductions OBJECTIVE To determine the most appropriate means to assess the response to treatment in terms of  pain and functional impairment in a chronic rheumatic condition ( knee osteoarthritis [ OA ] ) and an acute rheumatic condition ( rotator cuff syndrome [ RCS ] ) . METHODS Two prospect i ve studies were conducted consisting of 1,019 out patients with knee OA and 271 patients with acute RCS . The minimal clinical ly important improvement and the patient acceptable symptom state were determined for knee OA pain using a visual analog scale , and for knee OA function using the Western Ontario and McMaster Universities Osteoarthritis Index function subscale ; for acute RCS pain , a numeral rating scale was used , and the Neer function subscale was used for RCS function . RESULTS The minimal clinical ly important improvement was shown to be the change required to achieve the patient acceptable symptom state , whatever the baseline level of symptom , the outcome ( pain or function ) , or type of condition ( chronic or acute ) . This acceptable state for pain was higher for chronic ( 27.0 - 36.4 across the baseline score ) than acute ( 16.7 - 24.1 ) conditions . The level of functional impairment considered satisfactory by patients with knee OA was higher for more disabled patients ( 43.1 ) than for less disabled patients ( 20.4 ) . CONCLUSION Patients consider that they experienced an important improvement only if this improvement allowed them to achieve a state they consider satisfactory . The most appropriate means to assess the response to therapy seems to be to assess whether patients feel good ( i.e. , achieve the patient acceptable symptom state ) AIMS The results of clinical trials often seem to have little influence on the practice of individual doctors . This could be because trial information is presented in the style of a scientific experiment which can not often be clearly related to the context of everyday patient care . We tested the hypothesis that such framing effects would cause doctors to assess the clinical significance of treatment outcomes differently when presented as clinical trial results rather than as individual patient data . METHODS Fourteen rheumatologists independently review ed the same 50 sets of data obtained from patients with rheumatoid arthritis . The data consisted of 10 commonly used clinical and laboratory variables measured before and after a period of treatment . The same data were presented in two formats on two separate occasions . The patient data format was a collection of typed sheets attributing each set of results to an individual patient . The clinical trial format was a professionally printed and bound booklet in which each set of results was laid out as summary results of a small uncontrolled clinical trial . Doctors judged the degree of improvement or deterioration and its clinical importance for each data set for both formats . These changes were converted into units of ' Clinical Importance ' . RESULTS Although some statistically significant differences emerged in the individual doctors ' judgements between the formats none of these was of a clinical ly important size . The median of the mean trial -- patient difference between the formats for all 14 doctors was 0.035 units of clinical importance [ 95 % CI -0.244 to 0.074 ] . CONCLUSIONS This evidence does not support the hypothesis that framing effects are a major cause of the failure of clinical trials to influence clinical practice
target: Presentation of relative effects regarding pain will facilitate interpretation of treatment effects
background: OBJECTIVE Pain is a patient-important outcome , but current reporting in r and omized controlled trials and systematic review s is often suboptimal , impeding clinical interpretation and decision making .