![Decreased Pain Following use of a Topical Analgesic:
Interim Results from the Optimizing Patient Experience and Response to Topical Analgesics (OPERA) Observational Study
Jeffrey Gudin, MD1
, Michael Brennan, MD2
, Edmund Harris, MD3
, Peter Hurwitz4
, Derek Dietze5
, Christopher Viereck, PhD5
1
Englewood Hospital and Medical Center, Englewood, NJ, 2
The Pain Center of Fairfield, Fairfield, CT, 3
Safe Harbor Compliance and Clinical Services, LLC, Austin, TX, 4
Clarity Research and Consulting, LLC, Narragansett, RI, 5
Metrics for Learning, LLC, Queen Creek, AZ
Mean 賊 SD Range
Female/Male (n) 383/248
Age at Survey 1 (years) 46.3 賊 11.1 18.2 64.3
Days between Surveys 1 & 3 75.5 賊 22.5 40 140
SD = standard deviation
Table 1. Patient Characteristics (n= 631 for each)
Side Effect % n
No side effect 99.5% 628
Rash 0.5% 3
Other 0.0% 0
Total 100% 631
Table 2. Patient-Reported Side Effects Associated with Topical Analgesics
46.4%
50.7%
65.5%
30.9%
20.4%
36.8%
39.8%
59.6%
31.1%
15.5%
0%
10%
20%
30%
40%
50%
60%
70%
Arthritis Neuropathy or Radiculopathy Myofascial/Musculoskeletal Pain or
Spasm
Tendinitis Other
Survey 1 Survey 3
21.5%
Decrease
9.0%
Decrease
0.6%
Increase
24.0%
Decrease
Percent
20.7%
Decrease
P<.001 P<.001
P=.008
P=1.000
P=.009
Figure 1. Changes in Percentage of Patient-Reported Primary Pain Complaints/Symptoms from
Survey 1 to Survey 3 (n= 631 for each, paired data by each separate complaint)
6.6
3.2
5.0
4.5 4.84.9
2.0
3.3 3.0 3.3
0
1
2
3
4
5
6
7
8
9
10
Pain at its worst in the last
24 hours
Pain at its least in the last
24 hours
Pain on the average Pain you have right now Overall Severity Score
Survey 1 Survey 3
37.5%
Decrease
34.0%
Decrease
33.3%
Decrease
31.3%
Decrease
*
*
* * *
BPIRating(010Scale)**
25.8%
Decrease
BPI Severity Component
**Average score on a scale of 0 = No pain, to 10 = Pain as bad as you can imagine.
*P<.001
Figure 2. Change in Mean Overall BPI Severity Score and 4 Components of the BPI Severity Score from
Survey 1 to Survey 3 (paired data, n= 631 for each)
66.2%
28.7%
24.4%
32.2%
10.3%
17.7%
0%
10%
20%
30%
40%
50%
60%
70%
80%
Over the Counter Anti Inflammatory (Rx) Opioids
Survey 1 Survey 3
64.1%
Decrease
27.5%
Decrease
Percent
51.4%
Decrease
*P<.001
*
*
*
Figure 4. Change in Reported Use of Oral Pain Medications from Survey 1 to Survey 3 by Type
(n= 631 for each, paired data)
Yes
95%
No
5%
Easy to apply (n= 627)
Yes
86%
No
14%
Convenient (n= 626)
Yes
76%
No
24%
Preferred over oral
medication (n= 618)
Very
50%
Somewhat
42%
Not at all
8%
Overall satisfaction with topical
analgesic (n= 624)
Figure 5. Patient-Reported Observations on the Use of Topical Analgesics
5.1
4.4 4.4
5.3
3.0
4.6 4.7 4.5
3.3
2.4
2.7
3.2
1.7
2.8 2.6 2.7
0
1
2
3
4
5
6
7
8
9
10
General Activity Mood Walking Ability Normal work Relations with other
people
Sleep Enjoyment of life Overall Interference
Score
Survey 1 Survey 3
*P<.001
**Average score on a scale of 0 = Does not Interfere, to 10 = Completely Interferes
BPI Interference Component
35.3%35.3% 45.5%45.5% 38.6%38.6% 39.6%39.6% 43.3%43.3% 39.1%39.1% 44.7%44.7% 40.0%40.0%
BPIRating(010Scale)**
* * * * ** * *
Figure 3. Change in Mean Overall BPI Interference Score and 7 Components of the BPI Interference
Score from Survey 1 to Survey 3 (paired data, n= 631 for each)
Chronic, noncancer pain affects over 100 million Americans and is one of the most frequent reasons for individuals to seek medical
care.1
Although achieving pain relief and improved quality of life are the primary clinical goals, most patients and healthcare
professionals recognize, and the literature supports, 30% pain improvement to be clinically significanta success level that would
be unacceptable in other areas of medicine.2
Despite a wealth of treatment options, as many as 40% of patients treated for chronic
pain do not attain adequate analgesia, which can lead to physical and social dysfunction and diminished quality of life.1
Further compounding the issue, patients who experience chronic pain often have multiple comorbidities and take multiple
medications. Unfortunately, most pain therapies, including opioids and NSAIDs, are associated with adverse effects and the addition
of further systemic medications to control pain increases the risk of drug-drug interactions and side effects.3,4
Moreover, opioids are
subject to regulatory control due to the risk of abuse, misuse, and/or diversion, and therefore may not be appropriate for all patients.
Successful pain management must provide adequate analgesia without excessive adverse effects or risk.
Topical analgesics have the advantage of local application with limited systemic levels of drug.3
Because of the lower systemic
exposure observed with topical therapies, there may be a benefit from reduced side effects, a lower risk of drug-drug interactions,
and improved tolerability.3,5
Therefore, evaluation of opioid-sparing treatments including topical compounded formulations is critical
to identification of safer and more effective approaches to the treatment of pain.
Introduction
OPERA is an ongoing observational survey study of patients ages 18-64 who experience chronic neuropathic or musculoskeletal
pain and who have been prescribed a topical analgesic (Flurbiprofen 20%, Amitriptyline 5%, Magnesium Chloride 10%, Gabapentin
6%, Bupivicaine 2% or other pain-relieving transdermal cream). The study protocol did not dictate the treatment decisions for the
patients (i.e., number of applications per day). Most of the patients had been prescribed opioids or other oral analgesics, or were
taking over-the-counter medications for chronic pain.
The purpose of the pre-planned interim analysis of the OPERA study reported here was to:
1. Validate findings from a previous 2015 interim analysis (n= 417)
2. Evaluate the efficacy of the topical analgesic in reducing pain in patients experiencing either neuropathic or musculoskeletal pain,
using the Brief Pain Inventory (BPI) Short Form,6
3. Assess changes in the percentage of patient-reported primary pain complaints/symptoms,
4. Assess patient satisfaction with the topical analgesic, and
5. Identify any adverse effects.
Purpose
Results from this interim analysis suggest that the topical analgesics used in this study may:
Reduce BPI Severity and Interference scores for adult patients with neuropathic and musculoskeletal pain.
Reduce the number of primary pain complaints for each of arthritis, neuropathy or radiculopathy, and myofascial/
musculoskeletal pain or spasm.
Reduce the use of oral OTC, anti-inflammatory and opioid analgesics.
Overall patient satisfaction with topical analgesics was high.
Topical analgesics were safe and well-tolerated.
Findings were consistent with previous interim analysis results, and include 32 more investigators and 214 more patients.
Results from the interim analysis warrant and justify continuation of the OPERA trial.
Conclusions
This was an interim analysis. A more detailed analysis will be conducted at the conclusion of the study.
Results include all respondents, regardless of number/types of complaints/symptoms and regardless of number/types of oral pain
medications currently being taken.
This is an observational study; Changes observed cannot definitively be attributed to the topical analgesic. Further study is
therefore required.
Limitations
1. Institute of Medicine Report from the Committee on Advancing Pain Research, Care, and Education: Relieving Pain in America,
A Blueprint for Transforming Prevention, Care, Education and Research. The National Academies Press, 2011.
2. Farrar JT, Young JP, LaMoreaux L, et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical
pain rating scale. Pain. 2001;94:149158.
3. Peppin JF, Albrecht PJ, Argoff C et al. Skin Matters: A Review of Topical Treatments for Chronic Pain. Part One: Skin Physiology
and Delivery Systems. Pain Ther. 2015 Jan 28. [Epub ahead of print]
4. Wehling M. Non-steroidal anti-inflammatory drug use in chronic pain conditions with special emphasis on the elderly and patients
with relevant comorbidities: management and mitigation of risks and adverse effects. Eur J Clin Pharmacol. 2014;70:1159-72.
5. Schug SA and Goddard C. Recent advances in the pharmacological management of acute and chronic pain. Ann Palliat Med.
2014;3:263-75.
6. Cleeland CS. The Brief Pain Index, Short Form. 1991. Pain Research Group.
References
Following IRB approval and patient consent, data were collected beginning in 2014 via paper survey forms completed by study
participants from 85 physicians who treat patients with chronic pain. The top four physician specialties were: anesthesiology, general
medicine, pain management, and podiatry. Physician practices were in 12 different states across the USA.
Observation Study Design
Survey 1 (at first patient visit before use of topical analgesic):
Questions regarding primary pain complaint/symptoms (and location)
The BPI Short Form (Severity and Interference components)used with permission from MD Anderson.
Current medication usage
Survey 2 (at second patient visitapproximately 45 days since starting use of the topical analgesic):
Data not used for this interim analysis. Study designed called for an analysis at approximately half way through the entire study
(at Survey 3). A more in-depth summative analysis will be conducted at study conclusion.
Same questions as used for Survey 3 below
Survey 3 (at third patient visitapproximately 90 days since starting use of the topical analgesic):
All Survey 1 questions
Questions related to use of the topical analgesic
All Surveys included queries on any side effects of the topical analgesic.
Completed forms were collected and entered into Microsoft Excel.
For patients with days between Survey 1 and Survey 3 40 and 140, Survey 1 and Survey 3 records were matched using a
unique identifier = 723 records.
Records were removed due to incomplete/misaligned data = 92 records.
Total records used in this interim analysis = 631 paired records.
Data were transferred from Excel into the Statistics Package for the Social Sciences (SPSS, IBM, version 23) for statistical analysis.
Descriptive statistics were run for all questions. Statistically significant differences between Survey 1 and Survey 3 results were
calculated using the McNemar test for binomial data and the Wilcoxon Signed Ranks test for scale data. Alpha was set at .05.
Methods
Study funded by:
Annie's Apothecary, Kerrville, TX
Annies Apothecary, Boerne, TX
Boothwyn Pharmacy, Boothwyn, PA
Cypress Compounding Pharmacy, Houston, TX
Correspondence
Peter Hurwitz: peterh@crcsciences.com
Financial Disclosures
J. Gudin: Honoraria paid by Clarity Research and Consulting, LLC
M. Brennan: Honoraria paid by Clarity Research and Consulting, LLC
E. Harris: Consultant to Clarity Research and Consulting, LLC
P. Hurwitz: Study funded by the 4 pharmacies listed above
D. Dietze: Analysis paid by Clarity Research and Consulting, LLC
C. Viereck: Analysis paid by Clarity Research and Consulting, LLC
Poster #196, American Academy of Pain Medicine 32nd Annual Meeting, February 18-21, 2016, Palm Springs, CA
Results
Further analysis is needed, as 55% of patients reported more than one primary complaint (Survey 1 mean = 2.1 complaints,
Survey 3 mean = 1.8 complaints, statistically significant decrease: P<.001, n= 631, paired data).
None of the side effects reported were serious adverse events](https://image.slidesharecdn.com/aa9babf3-4f08-4977-936b-50becafb1632-160615191422/85/clarity-study-1-320.jpg)
clarity study
- 1. Decreased Pain Following use of a Topical Analgesic: Interim Results from the Optimizing Patient Experience and Response to Topical Analgesics (OPERA) Observational Study Jeffrey Gudin, MD1 , Michael Brennan, MD2 , Edmund Harris, MD3 , Peter Hurwitz4 , Derek Dietze5 , Christopher Viereck, PhD5 1 Englewood Hospital and Medical Center, Englewood, NJ, 2 The Pain Center of Fairfield, Fairfield, CT, 3 Safe Harbor Compliance and Clinical Services, LLC, Austin, TX, 4 Clarity Research and Consulting, LLC, Narragansett, RI, 5 Metrics for Learning, LLC, Queen Creek, AZ Mean 賊 SD Range Female/Male (n) 383/248 Age at Survey 1 (years) 46.3 賊 11.1 18.2 64.3 Days between Surveys 1 & 3 75.5 賊 22.5 40 140 SD = standard deviation Table 1. Patient Characteristics (n= 631 for each) Side Effect % n No side effect 99.5% 628 Rash 0.5% 3 Other 0.0% 0 Total 100% 631 Table 2. Patient-Reported Side Effects Associated with Topical Analgesics 46.4% 50.7% 65.5% 30.9% 20.4% 36.8% 39.8% 59.6% 31.1% 15.5% 0% 10% 20% 30% 40% 50% 60% 70% Arthritis Neuropathy or Radiculopathy Myofascial/Musculoskeletal Pain or Spasm Tendinitis Other Survey 1 Survey 3 21.5% Decrease 9.0% Decrease 0.6% Increase 24.0% Decrease Percent 20.7% Decrease P<.001 P<.001 P=.008 P=1.000 P=.009 Figure 1. Changes in Percentage of Patient-Reported Primary Pain Complaints/Symptoms from Survey 1 to Survey 3 (n= 631 for each, paired data by each separate complaint) 6.6 3.2 5.0 4.5 4.84.9 2.0 3.3 3.0 3.3 0 1 2 3 4 5 6 7 8 9 10 Pain at its worst in the last 24 hours Pain at its least in the last 24 hours Pain on the average Pain you have right now Overall Severity Score Survey 1 Survey 3 37.5% Decrease 34.0% Decrease 33.3% Decrease 31.3% Decrease * * * * * BPIRating(010Scale)** 25.8% Decrease BPI Severity Component **Average score on a scale of 0 = No pain, to 10 = Pain as bad as you can imagine. *P<.001 Figure 2. Change in Mean Overall BPI Severity Score and 4 Components of the BPI Severity Score from Survey 1 to Survey 3 (paired data, n= 631 for each) 66.2% 28.7% 24.4% 32.2% 10.3% 17.7% 0% 10% 20% 30% 40% 50% 60% 70% 80% Over the Counter Anti Inflammatory (Rx) Opioids Survey 1 Survey 3 64.1% Decrease 27.5% Decrease Percent 51.4% Decrease *P<.001 * * * Figure 4. Change in Reported Use of Oral Pain Medications from Survey 1 to Survey 3 by Type (n= 631 for each, paired data) Yes 95% No 5% Easy to apply (n= 627) Yes 86% No 14% Convenient (n= 626) Yes 76% No 24% Preferred over oral medication (n= 618) Very 50% Somewhat 42% Not at all 8% Overall satisfaction with topical analgesic (n= 624) Figure 5. Patient-Reported Observations on the Use of Topical Analgesics 5.1 4.4 4.4 5.3 3.0 4.6 4.7 4.5 3.3 2.4 2.7 3.2 1.7 2.8 2.6 2.7 0 1 2 3 4 5 6 7 8 9 10 General Activity Mood Walking Ability Normal work Relations with other people Sleep Enjoyment of life Overall Interference Score Survey 1 Survey 3 *P<.001 **Average score on a scale of 0 = Does not Interfere, to 10 = Completely Interferes BPI Interference Component 35.3%35.3% 45.5%45.5% 38.6%38.6% 39.6%39.6% 43.3%43.3% 39.1%39.1% 44.7%44.7% 40.0%40.0% BPIRating(010Scale)** * * * * ** * * Figure 3. Change in Mean Overall BPI Interference Score and 7 Components of the BPI Interference Score from Survey 1 to Survey 3 (paired data, n= 631 for each) Chronic, noncancer pain affects over 100 million Americans and is one of the most frequent reasons for individuals to seek medical care.1 Although achieving pain relief and improved quality of life are the primary clinical goals, most patients and healthcare professionals recognize, and the literature supports, 30% pain improvement to be clinically significanta success level that would be unacceptable in other areas of medicine.2 Despite a wealth of treatment options, as many as 40% of patients treated for chronic pain do not attain adequate analgesia, which can lead to physical and social dysfunction and diminished quality of life.1 Further compounding the issue, patients who experience chronic pain often have multiple comorbidities and take multiple medications. Unfortunately, most pain therapies, including opioids and NSAIDs, are associated with adverse effects and the addition of further systemic medications to control pain increases the risk of drug-drug interactions and side effects.3,4 Moreover, opioids are subject to regulatory control due to the risk of abuse, misuse, and/or diversion, and therefore may not be appropriate for all patients. Successful pain management must provide adequate analgesia without excessive adverse effects or risk. Topical analgesics have the advantage of local application with limited systemic levels of drug.3 Because of the lower systemic exposure observed with topical therapies, there may be a benefit from reduced side effects, a lower risk of drug-drug interactions, and improved tolerability.3,5 Therefore, evaluation of opioid-sparing treatments including topical compounded formulations is critical to identification of safer and more effective approaches to the treatment of pain. Introduction OPERA is an ongoing observational survey study of patients ages 18-64 who experience chronic neuropathic or musculoskeletal pain and who have been prescribed a topical analgesic (Flurbiprofen 20%, Amitriptyline 5%, Magnesium Chloride 10%, Gabapentin 6%, Bupivicaine 2% or other pain-relieving transdermal cream). The study protocol did not dictate the treatment decisions for the patients (i.e., number of applications per day). Most of the patients had been prescribed opioids or other oral analgesics, or were taking over-the-counter medications for chronic pain. The purpose of the pre-planned interim analysis of the OPERA study reported here was to: 1. Validate findings from a previous 2015 interim analysis (n= 417) 2. Evaluate the efficacy of the topical analgesic in reducing pain in patients experiencing either neuropathic or musculoskeletal pain, using the Brief Pain Inventory (BPI) Short Form,6 3. Assess changes in the percentage of patient-reported primary pain complaints/symptoms, 4. Assess patient satisfaction with the topical analgesic, and 5. Identify any adverse effects. Purpose Results from this interim analysis suggest that the topical analgesics used in this study may: Reduce BPI Severity and Interference scores for adult patients with neuropathic and musculoskeletal pain. Reduce the number of primary pain complaints for each of arthritis, neuropathy or radiculopathy, and myofascial/ musculoskeletal pain or spasm. Reduce the use of oral OTC, anti-inflammatory and opioid analgesics. Overall patient satisfaction with topical analgesics was high. Topical analgesics were safe and well-tolerated. Findings were consistent with previous interim analysis results, and include 32 more investigators and 214 more patients. Results from the interim analysis warrant and justify continuation of the OPERA trial. Conclusions This was an interim analysis. A more detailed analysis will be conducted at the conclusion of the study. Results include all respondents, regardless of number/types of complaints/symptoms and regardless of number/types of oral pain medications currently being taken. This is an observational study; Changes observed cannot definitively be attributed to the topical analgesic. Further study is therefore required. Limitations 1. Institute of Medicine Report from the Committee on Advancing Pain Research, Care, and Education: Relieving Pain in America, A Blueprint for Transforming Prevention, Care, Education and Research. The National Academies Press, 2011. 2. Farrar JT, Young JP, LaMoreaux L, et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001;94:149158. 3. Peppin JF, Albrecht PJ, Argoff C et al. Skin Matters: A Review of Topical Treatments for Chronic Pain. Part One: Skin Physiology and Delivery Systems. Pain Ther. 2015 Jan 28. [Epub ahead of print] 4. Wehling M. Non-steroidal anti-inflammatory drug use in chronic pain conditions with special emphasis on the elderly and patients with relevant comorbidities: management and mitigation of risks and adverse effects. Eur J Clin Pharmacol. 2014;70:1159-72. 5. Schug SA and Goddard C. Recent advances in the pharmacological management of acute and chronic pain. Ann Palliat Med. 2014;3:263-75. 6. Cleeland CS. The Brief Pain Index, Short Form. 1991. Pain Research Group. References Following IRB approval and patient consent, data were collected beginning in 2014 via paper survey forms completed by study participants from 85 physicians who treat patients with chronic pain. The top four physician specialties were: anesthesiology, general medicine, pain management, and podiatry. Physician practices were in 12 different states across the USA. Observation Study Design Survey 1 (at first patient visit before use of topical analgesic): Questions regarding primary pain complaint/symptoms (and location) The BPI Short Form (Severity and Interference components)used with permission from MD Anderson. Current medication usage Survey 2 (at second patient visitapproximately 45 days since starting use of the topical analgesic): Data not used for this interim analysis. Study designed called for an analysis at approximately half way through the entire study (at Survey 3). A more in-depth summative analysis will be conducted at study conclusion. Same questions as used for Survey 3 below Survey 3 (at third patient visitapproximately 90 days since starting use of the topical analgesic): All Survey 1 questions Questions related to use of the topical analgesic All Surveys included queries on any side effects of the topical analgesic. Completed forms were collected and entered into Microsoft Excel. For patients with days between Survey 1 and Survey 3 40 and 140, Survey 1 and Survey 3 records were matched using a unique identifier = 723 records. Records were removed due to incomplete/misaligned data = 92 records. Total records used in this interim analysis = 631 paired records. Data were transferred from Excel into the Statistics Package for the Social Sciences (SPSS, IBM, version 23) for statistical analysis. Descriptive statistics were run for all questions. Statistically significant differences between Survey 1 and Survey 3 results were calculated using the McNemar test for binomial data and the Wilcoxon Signed Ranks test for scale data. Alpha was set at .05. Methods Study funded by: Annie's Apothecary, Kerrville, TX Annies Apothecary, Boerne, TX Boothwyn Pharmacy, Boothwyn, PA Cypress Compounding Pharmacy, Houston, TX Correspondence Peter Hurwitz: peterh@crcsciences.com Financial Disclosures J. Gudin: Honoraria paid by Clarity Research and Consulting, LLC M. Brennan: Honoraria paid by Clarity Research and Consulting, LLC E. Harris: Consultant to Clarity Research and Consulting, LLC P. Hurwitz: Study funded by the 4 pharmacies listed above D. Dietze: Analysis paid by Clarity Research and Consulting, LLC C. Viereck: Analysis paid by Clarity Research and Consulting, LLC Poster #196, American Academy of Pain Medicine 32nd Annual Meeting, February 18-21, 2016, Palm Springs, CA Results Further analysis is needed, as 55% of patients reported more than one primary complaint (Survey 1 mean = 2.1 complaints, Survey 3 mean = 1.8 complaints, statistically significant decrease: P<.001, n= 631, paired data). None of the side effects reported were serious adverse events