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Database Data field extracted and used Time period or extract version Source Drug Shortages Canada Database DIN,* package size, actual shortage start date, shortage reasons (shortage of an active ingredient, shortage of an inactive ingredient or component, disruption of the manufacture of the drug, requirements related to complying with good manufacturing practices, delay in shipping of the drug, demand increase for the drug, or other), estimated shortage end date and actual shortage end date, if available Mar. 14, 2017 to Sept. 12, 2018 Drug Shortages Canada website (22) Drug Product Database DIN, drug name, active ingredient(s), strength, dosage form, route of administration, manufacturer, package size, Active Ingredient Group number,† Anatomic Therapeutic Chemical classification, schedule (e.g., prescription, Controlled Drugs and Substances Act, biological, over-the-counter, “ethical” products‡), market status (marketed, cancelled, dormant) and status date Data extracted were last updated by Health Canada on Apr. 12, 2019 Health Canada (24) Formulary data for 9 provinces in Canada§ DIN; brand generic code that indicates whether a drug is a brand, generic or biologic; plan or program; formulary coverage start date and end date and the listed price, if available April 2008 to Mar. 31, 2017 Canadian Institute for Health Information (25) PharmaClik DIN, package size¶ Catalogue downloaded on Oct. 10, 2018 McKesson Canada (26) Note: DIN = Drug Identification Number.
↵* DIN uniquely identifies a drug’s active ingredients, strength, dosage form, route of administration and manufacturer.
↵† A 10-digit number that identifies products that have the same active ingredient(s) and ingredient strength(s).
↵‡ Drugs that do not require a prescription but are generally prescribed by medical practitioners for unscheduled professional use and emergency use.
↵§ Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island and Saskatchewan.
↵¶ Used to supplement the package code information obtained from the Drug Product Database.
Variable Markets Branded DINs Generic DINs Total, n Markets in shortage, n (%) Shortage duration,* mean days ± SD Total, n DINs in shortage n (%) Shortage duration,* mean days ± SD Total, n DINs in shortage n (%) Shortage duration,* mean days ± SD All 3470 462 (13.3) 136.6 ±149.2 2322 426 (18.3) 99.9 ± 111.7 6527 1730 (26.5) 167.6 ± 149.1 Market structure B and G single 208 31 (14.9) 134.5 ± 131.2 235 64 (27.2) 120.4 ± 124.7 214 73 (34.1) 163.2 ± 160.9 B and G multiple 620 13 (2.1) 126.5 ± 142.3 681 131 (19.2) 100.0 ± 109.9 4423 1169 (26.4) 162.5 ± 144.9 G single 454 124 (27.3) 187.2 ± 169.2 464 127 (27.4) 188.2 ± 169.3 G multiple 387 36 (9.3) 130.0 ± 158.1 1426 361 (25.3) 177.9 ± 152.2 BIO 484 49 (10.1) 192.1 ± 184.6 B only 1317 209 (15.9) 95.6 ± 112.7 1406 231 (16.4) 94.1 ± 108.7 Route of administration or form Injection 991 119 (12.0) 168.5 ± 170.3 323 59 (18.3) 105.3 ± 108.1 640 151 (23.6) 181.8 ± 163.1 Oral nonsolid 189 44 (23.3) 159.4 ± 170.8 123 23 (18.7) 108.6 ± 123.2 134 40 (29.9) 188.4 ± 164.7 Oral solid regular release 1513 154 (10.2) 132.6 ± 149.8 1195 198 (16.6) 104.3 ± 119.2 4789 1239 (25.9) 165.3 ± 145.7 Oral solid special release 238 25 (10.5) 84.0 ± 108.8 254 39 (15.4) 75.2 ± 108.3 526 144 (27.4) 179.6 ± 160.0 Other 539 120 (22.3) 112.5 ± 115.1 427 107 (25.1) 95.8 ± 97.9 438 156 (35.6) 156.0 ± 147.4 Essential medicine No 2981 388 (13.0) 136.5 ± 149.0 1945 361 (18.6) 103.3 ± 114.7 4923 1277 (25.9) 167.5 ± 149.6 Yes 489 74 (15.1) 137.2 ± 151.1 377 65 (17.2) 80.9 ± 91.5 1604 453 (28.2) 167.9 ± 147.9 On formulary† No 878 107 (12.2) 153.6 ± 168.0 512 83 (16.2) 116.8 ± 131.7 1171 222 (19.0) 154.8 ± 142.6 Yes 2592 355 (13.7) 131.5 ± 142.9 1810 343 (19.0) 95.8 ± 106.1 5356 1508 (28.2) 169.5 ± 150.0 DIN age, yr < 3 250 8 (3.2) 102.4 ± 105.7 1154 193 (16.7) 183.1 ± 153.7 ≥ 3 2072 418 (20.2) 99.8 ± 111.9 5373 1537 (28.6) 165.7 ± 148.5 Top 50 manufacturers‡ No 520 85 (16.3) 119.2 ± 105.8 1942 358 (18.4) 173.7 ± 149.1 Yes 1802 341 (18.9) 95.1 ± 112.8 4585 1372 (29.9) 166.1 ± 149.2 Manufacturer size§ Small 731 78 (10.7) 115.8 ± 111.3 322 43 (13.4) 189.6 ± 186.8 Medium 682 143 (21.0) 112.4 ± 128.3 636 146 (23.0) 135.6 ± 119.5 Large 909 205 (22.6) 85.0 ± 97.1 5569 1541 (27.7) 170.1 ± 150.2 Note: B = branded manufacturer, BIO = biologic manufacturer, DIN = Drug Identification Number, G = generic manufacturer, SD = standard deviation.
↵* Shortage duration among those in shortage.
↵† On provincial formulary in at least 1 of the included provinces.
↵‡ Top 50 manufacturers by drug cost from public drug plans in Canada in 2017/18.
↵§ Manufacturer size was defined by the total number of DINs. Small: 1–40, Medium: 40–99, Large: 100+.
- Table 3:
Association between drug shortage and factors and its duration at the market level
Parameter or level Shortage Shortage duration* OR (95% CI) Coefficient (SE) p value Average marginal effect (95% CI)‡ Market structure (Ref.: B and G single) B and G multiple 0.13 (0.06 to 0.25) −0.18 (0.38) 0.639 −23.5 (−121 to 80.6) B only 1.15 (0.76 to 1.76) −0.17 (0.23) 0.465 −22.0 (−104 to 32.0) G single 1.99 (1.28 to 3.11) 0.51 (0.24) 0.034 95.9 (11.4 to 169.0) G multiple 0.57 (0.34 to 0.97) −0.19 (0.29) 0.502 −25.1 (−112 to 51.0) BIO 1.13 (0.65 to 1.97) 0.34 (0.32) 0.283 58.2 (−57.9 to 167.4) Overall p value† < 0.001 < 0.001 Route of administration or form (Ref.: oral solid regular release) Injection 1.14 (0.82 to 1.59) 0.05 (0.21) 0.831 7.2 (−58.2 to 75.7) Oral nonsolid 1.66 (1.11 to 2.49) 0.27 (0.21) 0.204 47.1 (−22.7 to 130.1) Oral solid special release 1.05 (0.66 to 1.68) 0.04 (0.27) 0.896 5.6 (−96.0 to 150.1) Other 1.31 (0.89 to 1.91) −0.01 (0.21) 0.942 −2.3 (−65.7 to 76.6) Overall p value† 0.151 0.758 Proportion of DINs on formulary Per 10% increase 1.03 (1.00 to 1.05) −0.02 (0.01) 0.071 −3.8 (−8.3 to 0.5)§ Anatomic Therapeutic Chemical Classification (Ref.: sensory organs) Alimentary tract and metabolism 0.20 (0.10 to 0.38) −0.40 (0.35) 0.255 −70.4 (−210 to 56.0) Blood and blood-forming organs 0.08 (0.03 to 0.22) −0.64 (0.56) 0.258 −100 (−262 to 100.9) Cardiovascular system 0.51 (0.28 to 0.90) −0.31 (0.29) 0.281 −57.5 (−204 to 56.1) Dermatologicals 0.36 (0.20 to 0.64) −0.07 (0.29) 0.803 −14.7 (−135 to 108.8) Genitourinary system and sex hormones 0.55 (0.31 to 0.98) −0.36 (0.30) 0.230 −64.2 (−196 to 46.1) Systemic hormonal preparations, excluding sex hormones and insulins 0.30 (0.15 to 0.59) −0.41 (0.38) 0.287 −71.2 (−216 to 67.5) Anti-infectives for systemic use 0.43 (0.25 to 0.74) −0.33 (0.31) 0.287 −59.7 (−194 to 51.9) Antineoplastic and immunomodulating agents 0.18 (0.10 to 0.34) −0.53 (0.37) 0.148 −88.3 (−232 to 54.7) Musculoskeletal system 0.35 (0.17 to 0.73) −0.01 (0.37) 0.970 −2.9 (−155 to 144.7) Nervous system 0.35 (0.21 to 0.59) −0.23 (0.28) 0.399 −44.5 (−170 to 65.4) Antiparasitic products, insecticides and repellents 0.55 (0.10 to 2.89) −1.03 (0.85) 0.225 −137 (−282 to −2.5) Respiratory system 0.58 (0.34 to 0.99) −0.44 (0.28) 0.111 −75.8 (−191 to 12.6) Various 0.22 (0.11 to 0.47) −0.18 (0.44) 0.676 −35.4 (−189 to 144.4) Overall p value† < 0.001 0.955 Model fit statistics C-statistic 0.73 AIC 2487.90 5540.4 Log-likelihood −1219.95 −2745.2 Note: AIC = Akaike information criteria, B = branded manufacturer, BIO = biologic manufacturer, CI = confidence interval, DIN = Drug Identification Number, G = generic manufacturer, OR = odds ratio, Ref. = reference category (0 or 1 as appropriate), SE = standard error.
↵* Results were based on truncated negative binomial regression models among markets in shortage.
↵† Based on type III Wald Test for shortage and type III likelihood ratio test for shortage duration.
↵‡ The average marginal effect of a variable was evaluated as the average of predicted differences (from the reference group) at observed values of covariates for each observation; 95% CI were the bootstrap confidence intervals based on 2000 bootstrap samples.
↵§ For an increase from 80% to 90%.
- Table 4:
Association between drug shortage and factors at the DIN level
Parameter or level Branded DINs
OR (95% CI)Generic DINs
OR (95% CI)Market structure (Ref.: B and G single) B and G multiple 0.65 (0.45 to 0.94) 0.68 (0.49 to 0.93) B only 0.68 (0.48 to 0.95) G single 0.65 (0.45 to 0.93) G multiple 0.62 (0.45 to 0.86) Overall p value* 0.048 0.036 DIN age (every year increase) 1.02 (1.02 to 1.03) DIN age, yr (Ref.: < 3) ≥ 3 1.85 (1.55 to 2.21) Route of administration or form (Ref.: oral solid regular release) Injection 1.16 (0.80 to 1.70) 1.29 (1.00 to 1.66) Oral nonsolid 1.12 (0.67 to 1.89) 1.09 (0.73 to 1.65) Oral solid special release 0.87 (0.59 to 1.28) 1.17 (0.94 to 1.45) Other 1.28 (0.84 to 1.94) 1.23 (0.87 to 1.72) Overall p value* 0.603 0.165 Interaction of manufacturer type and top 50 manufacturer (Ref.: branded = yes, top 50 = yes) Branded = no, top 50 = no 3.22 (1.91 to 5.44) Branded = no, top 50 = yes 2.23 (1.50 to 3.31) Branded = yes, top 50 = no 1.59 (1.13 to 2.25) Overall p value* < 0.001 Interaction of manufacturer size and top 50 manufacturer (Ref.: small) Large, top 50 = no 1.82 (1.25 to 2.64) Large, top 50 = yes 2.40 (1.71 to 3.38) Medium, top 50 = no 2.16 (1.45 to 3.23) Medium, top 50 = yes 2.41 (1.39 to 4.17) Overall p value* < 0.001 Essential medicine (Ref.: no) Yes 1.13 (0.99 to 1.30) Number of provinces on formulary (weighted) 1.09 (1.07 to 1.11) Anatomic Therapeutic Chemical Classification (Ref.: sensory organs) Alimentary tract and metabolism 0.40 (0.20 to 0.81) 0.30 (0.18 to 0.50) Blood and blood-forming organs 0.35 (0.14 to 0.86) 0.12 (0.05 to 0.30) Cardiovascular system 0.57 (0.30 to 1.10) 0.35 (0.22 to 0.56) Dermatologicals 0.51 (0.28 to 0.94) 0.37 (0.22 to 0.64) Genitourinary system and sex hormones 0.45 (0.23 to 0.85) 0.42 (0.25 to 0.71) Systemic hormonal preparations, excluding sex hormones and insulins 0.22 (0.10 to 0.51) 0.35 (0.18 to 0.70) Anti-infectives for systemic use 0.31 (0.15 to 0.62) 0.41 (0.25 to 0.67) Antineoplastic and immunomodulating agents 0.22 (0.11 to 0.45) 0.36 (0.21 to 0.63) Musculoskeletal system 0.63 (0.27 to 1.43) 0.27 (0.16 to 0.45) Nervous system 0.43 (0.23 to 0.79) 0.40 (0.25 to 0.64) Antiparasitic products, insecticides and repellents 0.60 (0.10 to 3.60) 0.28 (0.08 to 0.92) Respiratory system 0.64 (0.34 to 1.21) 0.48 (0.29 to 0.81) Various 0.30 (0.09 to 0.97) 0.46 (0.17 to 1.23) Overall p value* 0.004 < 0.001 Model fit statistics C-statistic 0.68 0.64 AIC 2126.38 7278.45 Log-likelihood −1038.19 −3611.23 Note: AIC = Akaike information criteria, B = branded manufacturer, CI = confidence interval, DIN = Drug Identification Number, G = generic manufacturer, OR = odds ratio, Ref.= reference category.
↵* Based on type III Wald Test.
- Table 5:
Association between duration of drug shortage and factors at the DIN level among those in shortage
Parameter or level Branded DINs Generic DINs Coefficient (SE) p value Average marginal effect (95% CI)‡ Coefficient (SE) p value Average marginal effect (95% CI)‡ Market structure (Ref.: B and G single) B and G multiple 0.01 (0.17) 0.958 1.4 (−57.7 to 59.2) −0.24 (0.12) 0.049 −47.5 (−103 to 5.5) B only −0.46 (0.17) 0.007 −58.1 (−117 to −8.6) G single −0.09 (0.14) 0.507 −20.2 (−81.8 to 36.7) G multiple −0.10 (0.13) 0.433 −21.1 (−77.2 to 33.8) BIO Overall p value* 0.002 0.040 Route of administration or form (Ref.: oral solid regular release) Injection −0.03 (0.21) 0.882 −3.5 (−49.3 to 50.0) 0.15 (0.10) 0.135 28.9 (−7.2 to 66.2) Oral nonsolid 0.15 (0.26) 0.576 18.0 (−46.1 to 103.6) 0.30 (0.17) 0.070 64.9 (6.8 to 137.9) Oral solid special release −0.68 (0.20) 0.001 −56.6 (−88.5 to −24.6) 0.12 (0.08) 0.163 22.7 (−7.3 to 56.3) Other 0.55 (0.23) 0.014 85.4 (10.6 to 189.8) −0.19 (0.15) 0.223 −31.0 (−79.1 to 25.4) Overall p value* 0.001 0.067 Reason for shortage Disruption of manufacture (Ref.: no) 0.49 (0.14) < 0.001 62.5 (26.2 to 106.7) 0.28 (0.08) < 0.001 48.8 (26.2 to 72.1) Shortage of ingredient (Ref.: no) 0.90 (0.24) < 0.001 161.6 (68.7 to 324.7) Delay in shipping (Ref.: no) −0.46 (0.16) 0.004 −47.9 (−78.6 to −13.6) −0.15 (0.08) 0.074 −26.4 (−51.0 to 1.5) Demand increase (Ref.: no) −0.12 (0.15) 0.429 −14.3 (−46.1 to 31.0) −0.49 (0.1) < 0.001 −74.4 (−95.2 to −49.3) Business reason (Ref.: no) 1.65 (0.33) < 0.001 494.0 (264.2 to 959.0) 0.78 (0.18) < 0.001 213.1 (127.3 to 313.0) Compliance† (Ref.: no) −0.08 (0.12) 0.526 −13.7 (−53.3 to 29.6) Anatomic Therapeutic Chemical Classification (Ref.: sensory organs) Alimentary tract and metabolism 0.58 (0.36) 0.108 66.1 (−20.4 to 167.7) −0.61 (0.20) 0.003 −175 (−341 to −60.9) Blood and blood-forming organs 0.18 (0.48) 0.708 16.7 (−53.2 to 135.5) −1.02 (0.39) 0.009 −243 (−433 to −92.9) Cardiovascular system 0.56 (0.30) 0.068 62.5 (−1.2 to 123.8) −0.70 (0.19) 0.000 −192 (−359 to −84.5) Dermatologicals 0.35 (0.27) 0.193 35.6 (−11.9 to 92.9) −0.45 (0.19) 0.020 −139 (−263 to −47.9) Genitourinary system and sex hormones 0.22 (0.29) 0.452 20.8 (−49.8 to 77.1) −0.81 (0.22) 0.000 −211 (−383 to −94.7) Systemic hormonal preparations, 0.19 (0.42) 0.652 17.5 (−51.5 to 105.8) −0.54 (0.28) 0.056 −159 (−340 to −24.6) excluding sex hormones and insulins Anti-infectives for systemic use 0.59 (0.36) 0.102 67.6 (−14.0 to 177.1) −0.76 (0.20) 0.000 −203 (−373 to −90.0) Antineoplastic and immunomodulating agents 0.45 (0.38) 0.242 47.5 (−43.3 to 161.9) −1.07 (0.23) < 0.0001 −251 (−421 to −139) Musculoskeletal system 0.81 (0.38) 0.032 104.6 (−4.9 to 235.3) −1.06 (0.21) < 0.0001 −249 (−416 to −139) Nervous system 0.33 (0.30) 0.269 33.3 (−29.0 to 90.2) −0.78 (0.19) < 0.0001 −206 (−371 to −101) Antiparasitic products, insecticides and repellents −0.22 (0.80) 0.787 −16.4 (−87.5 to 70.2) −1.31 (0.50) 0.009 −278 (−457 to −152) Respiratory system 0.04 (0.30) 0.890 3.5 (−45.2 to 48.2) −0.39 (0.19) 0.035 −124 (−255 to −28.9) Various −0.40 (0.61) 0.511 −27.8 (−93.2 to 48.4) −1.40 (0.41) 0.001 −287 (−456 to −146) Overall p value* 0.445 < 0.001 DIN age, yr 0.01 (0.004) 0.001 1.6 (0.6 to 2.5)§ On formulary (Ref.: no) −0.59 (0.15) < 0.001 −88.8 (−151 to −45.8) Manufacturer size (Ref.: large) Small 0.86 (0.16) < 0.001 118.2 (63.0 to 188.0) Medium 0.45 (0.13) < 0.001 50.2 (17.8 to 85.0) Overall p value* < 0.001 Model fit statistics AIC 4778.4 21251.2 Log-likelihood −2359.2 −10598.6 Note: AIC = Akaike information criteria, B = branded manufacturer, BIO = biologic manufacturer, CI = confidence interval, DIN = Drug Identification Number, G = generic manufacturer, Ref. = reference category, SE = standard error.
Results were based on truncated negative binomial regression models.
↵* Based on type III likelihood test.
↵† Requirement related to compliance with good manufacturing practices.
↵‡ The average marginal effect of a variable was evaluated as the average of predicted differences (from the reference category) at observed values of covariates for each observation; 95% CI were the bootstrap confidence intervals based on 2000 bootstrap samples.
↵§ For an increase from 20 years to 21 years.