Table 3.
Studies where drug holidays were observed. Drug holidays (DH), Medication event monitoring systems (MEMS).
| DRUG HOLIDAYS | |||||
|---|---|---|---|---|---|
| No | Studies | Types (N)/ Conditions | Remarks | Relevant Findings | Insight |
| 1 | Waterhouse, D. M., et al. (1993)(81) | Clinical Trial (24)/Cancers | Breast Cancers | 1in 24 (4%) - 14 days DH | No |
| Oral Tamoxifen | |||||
| 70 months follow-up | |||||
| 2 | Grigoryan, L., et al. (2013)(87) | Clinical Trial (120)/Hypertension | DH1 - single day omission. | 1. Patients taking 1 drug (n=57), DH3 – 8.8%, DH4 – 28.1%. | Yes |
| DH2 – 2 days, DH3 – 3 days, DH4 ≥ 4 days. | 2. Patients using 2 drugs (n=38), DH3 - D1 8%,D2 21% (Average 14.5%), DH4 – 50%,43% (Average 46.5%). | ||||
| 3. Patients using 3 drugs (n=25), DH3 – 0,8,8% (Average 5.3%), DH4 – 20,24,20% (Average 21.3%). | |||||
| 4. Omissions of 3 days made up on average 74% of all omissions. | |||||
| 3 | Kruse, W. and E. Weber (1990)(99) | Clinical Trial (31)/ Chronic medical conditions | MEMS | 1. DH in 50% and accounted for 15% of the monitoring period (1295 days). | 21 uninformed |
| 2. Fewer medication-free days were observed in patients who knew the purpose of the monitors than uninformed. | |||||
| 4 | Vrijens, B., et al. (2008)(86) | Clinical Trial (4783)/Hypertension | DH ≥ 3 days | 1. 43% | Unknown |
| 21 phase IV clinical studies | 2. Almost 50% had ≥1 DH/yr. | ||||
| MEMS | |||||
| (30 to 330 days) | |||||
| 5 | Brook, O. H., et al. (2006)(89) | Clinical Trial (119)/ Depression | DH ≥ 3 | 39/119 (33%) | Yes |
| consecutive days without dosing | |||||
| 9/128 (7%) defective MEMS. | |||||
| 6 | Wessels, A. M., et al. (2012)(90) | Clinical Trial (86)/Depression | DH ≥ 3 days | 1. 69% | Yes |
| 2. Average 3 DHs /patient | |||||
| 3. Average length of each DH - 7 days. | |||||
| 7 | Cramer, J. A., et al. (1990)(46) | Clinical Trial (20)/Epileptics | DH ≥ 1 day | 7/20 (35%) | Yes |
| MEMS bottles | |||||
| Drug levels - 30/37 in therapeutic range | |||||
| 8 | Ajit, R. R., et al. (2010)(91) | Clinical Trial (37)/Glaucoma | DH ≥ 8 days | 4/37 (11%) | Yes |
| Travatan Dosing Aid | |||||
| 9 | Cate, H., et al. (2015)(71) | Clinical Trial (208)/ Glaucoma | DH - No dosing > 6 days | 1. 22/159 (13.8%) | Yes |
| Travalert® dosing aid | 2. Non-adherent behaviour primarily due to DH. | ||||
| 10 | Kass, M. A., et al. (1986)(47) | Clinical Trial (184)/Glaucoma | No dosing ≥1 days | 45/184 (25%) | No |
| “Miniature compliance monitor” | |||||
| 11 | Riegel, B., et al. (2012)(88) | Clinical Trial (202)/Heart Failure | DH> 48hr | 47.5% in the first 3 months. | Yes |
| 12 | Deloria-Knoll, M., et al. (2004)(92) | Clinical Trial (255)/ HIV | DH≥2 days | 1. 28% ≥1 DH in the past year lasting an average of 23 days. | NA |
| Self-report | 2. 26%–44% less than a college degree reported a DH. | ||||
| 13 | Deschamps, A. E., et al. (2004)(79) | Clinical Trial (43)/ HIV | MEMS | DH median - 0.8/100 days | Yes |
| 14 | Parienti, J. J., et al. (2004)(20) | Clinical Trial (71)/ HIV | Self-report | 1. Repeated DHs (≥2) 19/71 (26.8%) | NA |
| 2. Repeated DH significantly a/w virologic failure and the development of resistance to the NNRTI class. | |||||
| 15 | Glass, T. R., et al. (2006)(93) | Survey (3607)/HIV | DH≥24 hours | 6% in the | NA |
| Self-report | previous 4 weeks. | ||||
| Swiss HIV Cohort Study | |||||
| 16 | Van Vaerenbergh, K., et al. (2002)(94) | Clinical Trial (41)/HIV | MEMS | 1. DH, median 1 (IQR: 4). | Yes |
| 4 months | 2. HAART responder(31)/non(10), DH (median) - 0/6.5 | ||||
| 17 | Touskova, T., et al. (2015)(85) | Clinical Trial (49)/Osteoporosis | 1. 71% of the patients took DHs. | No | |
| DH≥ 3 days | 2. DH > 7 days - 43%. | ||||
| 3. Overall compliance in patients with DH was 59% and was slightly lower on Fridays and on weekends. | |||||
| 18 | Touskova, T., et al. (2016)(95) | Clinical Trial (21)/Osteoporosis | DH≥ 3 days | 71% at baseline. | No |
| MEMS | 76% at follow-up in 1 yr. | ||||
| 19 | Pruijm, M., et al. (2009)(100) | Clinical Trial (7)/ Renal failure | DH - % of days per month on which the drug had not been taken at all. | 1. DH - 1% - 15.9% per drug per month. | Yes |
| Cinacalcet HCl, Calcium acetate, Sevelamer | 2. DH 1– 10 days. | ||||
| MEMS. | |||||
| 20 | Blowey, D. L., et al. (1997)(97) | Clinical Trial (19)/Renal transplant | DH ≥3 consecutive doses | 5/19 (26%) | Yes |
| MEMS | |||||
| 21 | Denhaerynck, K., et al. (2007)(101) | Clinical Trial (249)/Renal transplant | DH - > 48 h if once daily or for > 24 h if twice daily standardized over 100 days. | Mean number of DH per 100 monitored days - 1.1. | Yes |
| MEMS. | |||||
| 22 | Eberlin, M., et al. (2013)(98) | Clinical Trial (59)/Liver transplant | MEMS | DH - 13–32% | Yes |
| DH≥ 48hr | |||||
| 23 | Nevins, T. E. and W. Thomas (2009)(102) | Clinical Trial (137)/Renal transplant | DH≥ 48hr. | Patients in the highest tertile of missed drugs (≥5%) in the first 6 months are also those with more frequent and longer DH in the first 4 years. | Yes |
| MEMS | |||||
| 24 | Rodrigue, J. R., et al. (2013)(96) | Clinical Trial (236)/Liver transplant | DH ≥ 24 hours | 1. ≥1 24hr DH in 6 months - 71/236 (30%). | NA |
| Self-report | 2. Mean DHs in past 6 months - 4.4. | ||||
| 3. ≥1 48hr DH in 6 months - 38 (16%). | |||||
| 4. ≥1 72hr DH in 6 months - 23 (10%). | |||||