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.