Minimal clinically important difference

In the field of medical statistics, the minimal clinically important difference (also known as MCID), is a statistical model which tries to define the smallest change in a treatment outcome that a patient would identify as important.

Purpose

Over the years great steps have been taken in reporting what really matters in clinical research. As was still common in the sixties a clinical researcher might report: “in my own experience treatment X does not do well for condition Y”.[1][2] Conversely, as early as 1950 significance testing through the use of a P value cut off point of 0.05 was introduced by R.A. Fisher; this resulted in studies being either significant or non-significant.[3] Although this P value objectified research outcome, retaining to such a rigid cut off point can have two potentially serious consequences: (i) possibly clinically important differences observed in studies can be denoted as statistically non-significant and therefore be unfairly ignored as a result of having a small number of subjects studied (type II errors); (ii) even the smallest difference in measurements can be proved statistically significant by increasing the number of subjects in a study. Such a small difference could be irrelevant (i.e. of no clinical importance) to patients or clinicians. Thus, statistical significance does not necessarily imply clinical importance. Over the years clinicians and researchers have moved away from physical and radiological endpoints towards patient reported outcome. However, using patient reported outcome measurements does not solve the problem of small differences being statistical significance but possibly clinically irrelevant. In order to study clinical importance, the concept of minimal clinically important difference (MCID) has been proposed by Jaesche et al. in 1989.[4] MCID is the smallest change in an outcome that a patient would identify as important. MCID therefore offers a threshold above which outcome is experienced as relevant by the patient; this avoids the problem of mere statistical significance.

Methods of determining the MCID

Several techniques to calculate the MCID have been described and can be subdivided in roughly three categories: distribution-based methods, anchor-based methods and the Delphi method. There is no consensus regarding the optimal technique.

Distribution-based methods

These techniques are derived from statistical measures of spread of data: standard deviation, standard error of the mean and effect size (which is based on standard deviations)

  1. Using the one-half standard deviation benchmark of an outcome measure entails that patient improving more than one-half of the outcome score’s standard deviation have achieved a minimal clinically important difference.[5]
  2. The standard error of measurement is the variation in scores due to unreliability of the scale or measure used. Thus a change smaller than the standard error of measurement is likely to be the result of measurement error rather than a true observed change. Patients achieving a difference in outcome score of at least one standard error of measurement would have achieved a minimal clinically important difference.[6]
  3. The effect size is a measure obtained by dividing the difference between the means of the baseline and posttreatment scores by the SD of the baseline scores. An effect size cut off point can be used to define MCID in the same way as the one half standard deviation and the standard error of measurement.[6]

Anchor based

The anchor based method compares changes in scores with an “anchor” as reference. An anchor establishes if the patient is better after treatment compared to baseline according to the patients own experience. A popular anchor is the anchor question, at a specific point in time after treatment the patient might be asked: ‘‘Do you feel that you are improved by your treatment?’’.[7] Answers to anchor questions could vary from a simple “yes” or “no”, to everything in between, e.g. “much better”, “slightly better”, “about the same”, “somewhat worse” and “much worse”. The latter one are part of the Medical Outcomes Study Short Form-36 which is a tool often used for assessing MCID. An interesting approach to the anchor based method is establishment of an anchor before treatment. The patient is asked what minimal outcome would be necessary to undergo the proposed treatment. This method allows for more personal variation as one patient might require more pain relief, where another strives towards more functional improvement.[8] Different anchor questions and a different number of possible answers have been proposed. [9][8] Currently there is no consensus on the one right question nor on the best answers.

Delphi method

The Delphi method relies on a panel of experts who reach consensus regarding the MCID. The expert panel is provided with information on the results of a trial and are requested to provide their best estimate of the MCID. Their responses are averaged, and this summary is sent back with an invitation to revise their estimates. This process is continued until consensus is achieved.[10][11][12]

Shortcomings

Anchor based method is not suitable for conditions where most patients will improve and few remain unchanged. High post treatment satisfaction results in insufficient discriminative ability for calculation of a MCID.[2][13] A possible solution to this problem is a variation on the calculation of a 'substantial clinical benefit' score. This calculation is not based on the patients that improve vs. that do not, but on the patients that improve and those who improve a lot.[9]

MCID calculation is of limited additional value for treatments that show effects only in the long run, e.g. tightly regulated blood glucose in the case of diabetes might cause discomfort because of the accompanying hypoglycemia (low blood sugar) and the perceived quality of life might actually decrease; however, regulation reduces severe long term complications and is therefore still warranted. The calculated MCID varies widely depending on the method used,[14][15] currently there is no preferred method of establishing ‘the’ MCID.

Caveats

The MCID varies according to diseases and outcome instruments, but it does not depend on treatment methods. Therefore, two different treatments for a similar disease can be compared using the same MCID if the outcome measurement instrument is the same. Also MCID seems to differ over time after treatment for the same disease.[2]

See also

References

  1. ↑ Neviaser JS (1954). "Ruptures of the rotator cuff". Clin Orthop 3: 92–8. PMID 13161170.
  2. 1 2 3 Leopold SS (May 2013). "Editor's spotlight/take 5: Comparative responsiveness and minimal clinically important differences for idiopathic ulnar impaction syndrome". Clin. Orthop. Relat. Res. 471 (5): 1403–5. doi:10.1007/s11999-013-2886-x. PMC 3613524. PMID 23460486.
  3. ↑ Sterne JA, Davey Smith G (January 2001). "Sifting the evidence-what's wrong with significance tests?". BMJ 322 (7280): 226–31. doi:10.1136/bmj.322.7280.226. PMC 1119478. PMID 11159626.
  4. ↑ Jaeschke R, Singer J, Guyatt GH (December 1989). "Measurement of health status. Ascertaining the minimal clinically important difference". Control Clin Trials 10 (4): 407–15. doi:10.1016/0197-2456(89)90005-6. PMID 2691207.
  5. ↑ Norman GR, Sloan JA, Wyrwich KW (May 2003). "Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation". Med Care 41 (5): 582–92. doi:10.1097/01.MLR.0000062554.74615.4C. PMID 12719681.
  6. 1 2 Copay AG, Subach BR, Glassman SD, Polly DW, Schuler TC (2007). "Understanding the minimum clinically important difference: a review of concepts and methods". Spine J 7 (5): 541–6. doi:10.1016/j.spinee.2007.01.008. PMID 17448732.
  7. ↑ Kim JK, Park ES (May 2013). "Comparative responsiveness and minimal clinically important differences for idiopathic ulnar impaction syndrome". Clin. Orthop. Relat. Res. 471 (5): 1406–11. doi:10.1007/s11999-013-2843-8. PMC 3613518. PMID 23404422.
  8. 1 2 Carragee EJ, Cheng I (April 2010). "Minimum acceptable outcomes after lumbar spinal fusion". Spine J 10 (4): 313–20. doi:10.1016/j.spinee.2010.02.001. PMID 20362247.
  9. 1 2 Glassman SD, Copay AG, Berven SH, Polly DW, Subach BR, Carreon LY (September 2008). "Defining substantial clinical benefit following lumbar spine arthrodesis". J Bone Joint Surg Am 90 (9): 1839–47. doi:10.2106/JBJS.G.01095. PMID 18762642.
  10. ↑ Bellamy N, Carette S, Ford PM, Kean WF, le Riche NG, Lussier A, Wells GA, Campbell J (March 1992). "Osteoarthritis antirheumatic drug trials. III. Setting the delta for clinical trials--results of a consensus development (Delphi) exercise". J. Rheumatol. 19 (3): 451–7. PMID 1578462.
  11. ↑ Bellamy N, Anastassiades TP, Buchanan WW, Davis P, Lee P, McCain GA, Wells GA, Campbell J (December 1991). "Rheumatoid arthritis antirheumatic drug trials. III. Setting the delta for clinical trials of antirheumatic drugs--results of a consensus development (Delphi) exercise". J. Rheumatol. 18 (12): 1908–15. PMID 1795330.
  12. ↑ Bellamy N, Buchanan WW, Esdaile JM, Fam AG, Kean WF, Thompson JM, Wells GA, Campbell J (November 1991). "Ankylosing spondylitis antirheumatic drug trials. III. Setting the delta for clinical trials of antirheumatic drugs--results of a consensus development (Delphi) exercise". J. Rheumatol. 18 (11): 1716–22. PMID 1787494.
  13. ↑ Shauver MJ, Chung KC (March 2009). "The minimal clinically important difference of the Michigan hand outcomes questionnaire". J Hand Surg Am 34 (3): 509–14. doi:10.1016/j.jhsa.2008.11.001. PMID 19258150.
  14. ↑ Parker SL, Adogwa O, Mendenhall SK, Shau DN, Anderson WN, Cheng JS, Devin CJ, McGirt MJ (December 2012). "Determination of minimum clinically important difference (MCID) in pain, disability, and quality of life after revision fusion for symptomatic pseudoarthrosis". Spine J 12 (12): 1122–8. doi:10.1016/j.spinee.2012.10.006. PMID 23158968.
  15. ↑ Kosinski M, Zhao SZ, Dedhiya S, Osterhaus JT, Ware JE (July 2000). "Determining minimally important changes in generic and disease-specific health-related quality of life questionnaires in clinical trials of rheumatoid arthritis". Arthritis Rheum. 43 (7): 1478–87. doi:10.1002/1529-0131(200007)43:7<1478::AID-ANR10>3.0.CO;2-M. PMID 10902749.

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