A retrospective parallel group dual-cohort study of the German Pain e-Registry on the efficacy and safety of CBD-rich oral cannabis extract vs. THC/dronabinol in older patients with therapy-resistant or chronic pain "CARE"

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine, other:
  CBD>THC-full spectrum extract; THC/Dronabinol
• Study drug International non-proprietary name (INN) or common name:
  CANNABIDIOL

  DRONABINOL

Population studied

• Short description of the study population:
  Elderly patients (65 years of age or higher) with chronic and otherwise difficult-to-treat chronic pain
• Age groups:
  Elderly (≥ 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Estimated number of subjects:
  968

Study design details

• Study design:
  Retrospective, non-interventional evaluation of depersonalized routine-data provided by the German Pain e-Registry.
• Main study objective:
  Main objective of this non-interventional study is the comparative evaluation of safety, tolerability and efficacy of either CBD-rich cannabinoid full-spectrum extracts vs. pure THC/dronabinol extracts in elderly patients suffereing from chronic and elsewhere difficult-to-treat pain in daily practice. ; For this purpose routine-data of the German Pain e-Registry were mirrored according to defined in- and exclusion criteria, depersonalized and stratified into two treatment cohorts. To ensure comparable baseline findings, a so-called propensity score matching (PSM) is carried out, in which each patient treated with dronabinol/THC is matched with a patient treated with a CBD-rich oral extract [with regard to age, sex, pain phenotype, duration of illness, severity of impairment (according to von Korff), chronicity stage (according to the Mainz stage model) and analgesic co-medication (ATC group)] comparable patient is assigned to each patient treated with dronabinol/THC in a so-called “1:1 matching” (caliper 0.15, “without replacement”) (Note: Patients for whom no suitable “partner” from the other treatment group can be found in the PSM are excluded from the analysis without replacement; a PSM carried out on the basis of the above-mentioned target criteria on December 1, 2024 identified 484 evaluable patients with at least 6-month follow-up data for each of the two comparison groups). ; In addition to demographics and baseline data, treatment-related changes in pain intensity (least, mean, greatest 24-h pain intensity values, 24-h pain index - PIX), pain-related impairments (modified Pain Disability Index, mPDI), pain-related impairments of mood and affect (DASS-21, areas of depressiveness, anxiety and stress), pain-related restrictions on quality of life (Quality-of-Life Impairment by Pain Inventory, QLIP), as well as the daily cannabis dose and the need for or intake of other analgesics and co-analgesics for three evaluation points: baseline (i.e. immediately before the start of cannabis therapy) and at the end of months 3 and 6 under treatment.
• Setting:
  Patient data were split according to the cannabinoid treatments received and matched (as defined above) to harmonize them with respect to baseline parameters.
• Comparators:
  This study aims to compare the safety, tolerability and efficacy of a cannabinoid-based analgesic medication either with CBD>THC full spectrum oral extracts or pure THC/dronabinol over a period of 6 months.
• Outcomes:
  The primary endpoint is the absence of treatment discontinuation due to an ADR in conjunction with clinically relevant relief of pain (PIX) and pain-related impairment (mPDI; each with an improvement of at least 20 mm VAS and/or 30% vs. BL). ; All other efficacy parameters will be evaluated as secondary endpoints. ; The primary endpoint will be evaluated for the “as observed” data set (AOD) and as part of a sequential non-inferiority - superiority analysis). All other evaluations are based on a “last-observation carried forward” (for values “missing at random”, MAR) or “baseline observation carried forward” (for values “missing not at random”, MNAR; e.g. due to treatment discontinuation due to an adverse drug reaction) data set (LOCF/BOCF).
• Data analysis plan:
  The primary endpoint will be evaluated for the “as observed” data set (AOD) and as part of a sequential non-inferiority - superiority analysis). All other evaluations are based on a “last-observation carried forward” (for values “missing at random”, MAR) or “baseline observation carried forward” (for values “missing not at random”, MNAR; e.g. due to treatment discontinuation due to an adverse drug reaction) data set (LOCF/BOCF). All analyses base on a comparison of end of month 6 data vs. baseline.