Table 3 Chelation compliance measure and outcomes of published studies

Wolfe et al. 1985 [33]

Vials count

Frequency of DFO administration (≥ 5 days per week)

Compliant: 47.22% (n = 17)

Non-compliant: 52.78% (n = 19)

Compliant: reduced 𝛥 mean SF 1806 ± 760 ng/ml

Non-compliant group: increased 𝛥 mean SF 1040 ± 234ng/ml (p < 0.05).

Development of cardiac disease based on cardiac evaluation such as echocardiography & electrocardiography

Compliant group: 5.88% (n = 1).

Non-compliant group: 63.16% (n = 12).

Al-Refaie et al. 1992 [17]

Frequency of DFO administration.

Good compliance: DFO regularly for 4–5 nights weekly for 1 year.

Good compliance: 61.54% (n = 32)

Poor compliance: 38.46% (n = 20)

Compliant: mean SF 1454 ± 1242 ng/ml.

Non-compliant: mean SF 4686 ± 2866 ng/ml (p = 0.003).

Compliant: NTBI values ranged − 1.5 to 6.0 µmol/l.

Non-compliant: NTBI values ranged 2.1- 9.0µmol/l (p = 0.005).

Richardson et al. 1993 [34]

Vials count

Optimal compliance: >90%, Fair compliance: 50–90%, Poor compliance: <50% of prescribed DFO

Optimal compliance group: 60.53% (n = 46)

Fair compliance group: 22.37% (n = 17)

Poor compliance group: 17.10% (n = 13)

Compliance negatively proportional to SF with p < 0.001.

Development of cardiac disease based on cardiac evaluation such as echocardiography & electrocardiography

Optimal compliance: 30.43% (n = 14)

Fair compliance: 83.35% (n = 14)

Poor compliance: 69.23% (n = 9)

Higher risk of developing cardiac disease was associated with fair compliance (p < 0.001) and poor compliance (p = 0.016).

Compliance negatively proportional to liver iron (p < 0.001)

Arboretti et al. 2001 [18]

Percentage of DFO infusion over the year

Good compliance: >80%, fair compliance: 50–80%, poor compliance: <50% of insfusion per year.

good compliance group: 64% (n = 545)

fair compliance group: 27% (n = 236)

poor compliance group: 9% (n = 75)

11 missing data.

QoC questions:

Good compliance group: 14% scored below 6

Fair/poor compliance group: 22% of good compliance group scored below 6

QoL questions:

Good compliance group: 19% scored below 6

Fair/poor compliance group: 26% scored below 6.

Kidson-Gerber et al. 2008 [19]

Vials or pills count

The ratio of the amount dispensed to the prescribed dose over the year, classified into 0–24%, 25–49%, 50–74% and 75–100%.

Percentage DFO dispensed 75–100%: n = 9

Percentage DFO dispensed 50–74%: n = 12

Percentage DFO dispensed 25–49%: n = 8

Percentage DFO dispensed 0–24%: n = 14

Percentage DFO dispensed was inversely correlated with mean SF level with p < 0.001. Every 1% increase in DFO dispensed results in a reduction of 27 units in SF level. 28% of 0–24% DFO dispensed patients had high mean SF level which is more than 4000 ng/mL

Inverse association between cardiac and/or endocrine complication with compliance with p = 0.02.

Lee et al. 2011 [20]

Percentage of days of DFO therapy over a month.

Highly compliant (> 90%), moderately compliant (51–90%), poorly compliant (0.1–50%) and not compliant (0%).

Highly compliant: 31% (n = 43),

Moderately compliant: 50% (n = 70)

Poorly or non-compliant: 19% (n = 26)

Patients correlated to SF level more than 6000ng/mL

Compliant group: 38% (n = 14)

Moderately compliant group: 38% (n = 25)

Non-compliant group: 57% (n = 12)

However, no significant relationship between patient self-reported compliance and their latest SF level with p = 0.186.

Haghpanah et al. 2013 [21]

N/A

N/A

Good compliance: 85.1% (n = 86)

Poor compliance: 14.9% (n = 15)

SF-36 score (HRQoL)

Good compliant group: 69.8 ± 14.6

Poor compliant group: 56.1 ± 19.5

with p = 0.002

Mokhtar et al. 2013 [35]

Vials or pills count

Good compliance: <50%, fair compliance: 50–80%, and poor compliance: >80% of the drug was returned.

DFO

Non-compliance patients: 17.7% (n = 18)

DFP

Non-compliance patients 7.8% (n = 9)

DFX

Non-compliance patients: 0%

Based on clinical examination and echocardiography, non-compliant group had higher incidence of impaired left ventricular contractility with p = 0.021.

The incidence of hepatic morbidities was unaffected by compliance.

Non-compliance was associated with increased incidences of diabetes mellitus, hypogonadism, and mortality (p < 0.05, p < 0.05, p < 0.05)

Sobota et al. 2014 [23]

5-point Likert scale

1 = never, 2 = rarely, 3 = sometimes, 4 = often and 5 = a lot

Higher score indicated higher compliance.

N/A

Patient being transfused (general health domain only) and taking an oral chelator were related with higher HRQoL.

For patients taking DFO alone, there was no correlation between any measure of compliance and HRQOL.

Bazi et al. 2017 [24]

Frequency of ICT administration

Regular chelation: at least 27 out of 36 months

Regular compliance: 27.5% (n = 22)

Irregular chelation compliance: 71.3% (n = 57)

No chelation: 1.2% (n = 1).

PedQL4

Regular compliance:

PS: 56.66

Emo S: 75.00

SS: 25.68

ES: 51.33

Irregular compliance:

PS: 55.76

Emo S: 66.84

SS: 26.93

ES: 52.68

QoL was inversely associated with patients on irregular chelation (p = 0.004).

Overall, the total QoL score is 52.75 and 50.44 for regular and irregular chelation compliance.

Sobhani et al. 2019 [25]

Frequency of DFO administration or DFX consumption

Irregular users: <50 mg/kg/day (20 mg/kg/day in children) of DFO or < 30 mg/kg/day of DFX

Regular compliance: 67.8% (n = 61)

Irregular compliance:

32.2% (n = 29)

Patients with higher SF had 2.068 folds more probability to have high liver iron load with p = 0.001 and 1.87 folds more probability to have high cardiac iron load with p = 0.001.

Based on MRI T2*, patients with self-reported irregular use of iron chelating agents were more likely to have higher cardiac iron load. (p = 0.028)

Based on MRI T2*, patients with irregular compliance was not significantly associated with liver iron load. (p = 0.110)

Yassouf et al. 2019 [26]

Medication possession ratio (MPR).

Compliant: MPR of at least 0.80.

Compliant group:

54.9% (n = 45)

Non-compliant group: 45.1% (n = 37)

Mean SF level Compliant group: 3970.0 ± 1524.0 ng/mL

Non-compliant group: 6953.0 ± 2690.0 ng/mL

with significant difference p < 0.0001

TSH

Compliant group: 2.45 ± 0.96 lIU/mL

Non-compliant group: 4.38 ± 3.78 lIU/mL

(p < 0.001)

FT4

Compliant group: 1.25 ± 0.17 ng/dL

Non-compliant group: 1.14 ± 0.22 ng/dL)

(p < 0.005)

56.8% and 54.1% of DFO non-compliant patients having hypothyroidism and subclinical hypothyroidism with p < 0.0001 respectively

It was found that non-compliance with DFO treatment elevates the incidence of thyroid dysfunction about 6.38 times when compared to DFO compliance.

Sukhmani et al. 2020 [27]

4 point Likert Scale

Compliant: >75% of the prescribed doses ( score 1 and 2), non-compliant: <75% (score 3 and 4)

Compliance score

Compliant group

1: 26.5% (n = 57)

2: 62.8% (n = 135)

Non-compliant group

3: 10.2% (n = 22)

4: 0.5% (n = 1)

The compliance rate was highest with DFX (91.2%), followed by DFP (87.2%) and DFO (83.3%) (p = 0.350).

Mean SF level: compliant group: 2013.1 ± 1277.1 ng/mL

Non-compliant group: 3129.8 ± 1573.2 ng/mL

significantly lower with p = 0.000

Based on MRI T2*, cardiac iron overload were found higher in the non-compliant patients with p = 0.000

Based on MRI T2*, severe liver iron overload were found higher in the non-compliant patients with p = 0.021.

Theppornpitak et al. 2021 [28]

Thai version of the Morisky Medication Adherence Scales (MMAS-8)

Medium-low (> 1 score) and high groups (0 score).

High compliance level patient: 22.9% (n = 16)

Medium-low compliance level patient: 77.1% (n = 54)

𝛥 mean SF 6 months prior to enrolment

High compliance level: 276.4 ng/mL

Medium-low compliance level: 413.0 ng/mL

significant result with p = 0.034.

Badur et al. 2021 [32]

Frequency of using ICT

Never (did not use chelator), always (regular use of chelator) and sometimes (irregular use of chelator).

Did not use chelator: 11.1% (n = 3)

regularly compliance: 55.6% (n = 15)

irregularly compliance: 33.3% (n = 9)

There was no significant association among ICT compliance therapy and HRQoL with p = 0.552.

Mahmoud et al. 2021 [29]

Frequency of ICT administration

Good compliance: >50% of the calculated doses per month.

N/A

High serum ferritin levels were significantly associated with increased endocrine abnormalities with p = 0.003.

Patients received 50% or less than 50% medication monthly tend to have endocrine disorder. (67.86% vs. 32.14%) p = 0.03.

Increased endocrine abnormalities were significantly associated with poor ICT compliance p = 0.03.

Chai et al. 2021 [30]

Malay version of the Medication Compliance Questionnaire (MCQ).

Compliance:75% or higher.

Compliant group:

75.3% (n = 148)

Non-compliant group: 24.7% (n = 50)

Significant association was observed between SF level and compliance status with p = 0.007.

Amongst the non-compliant patients, 89.8% had serum ferritin level of ≥ 1000 mg/L compared with only 70.5% in patients who are compliant

There was no significant relationship between cardiac MRI findings and compliance with p = 0.908.

Liver MRI findings significantly associated with ICT compliance with p = 0.036.

Patients who were non-compliant had 23.8% moderate liver abnormality and 61.9% severe liver abnormality, compared to 17.9% and 41.8% of compliant patients with moderate and severe liver abnormality.

Lam et al. 2021 [31]

Standardized questionnaire (not mentioned)

N/A

> 80% compliance: 63.8% (n = 37)

50–80% compliance 27.6% (n = 16)

<50% compliance:8.6% (n = 5)

15 missing data

Cardiac iron loading was not significant associated with compliance. (p = 0.056)

Liver iron loading was not significant associated with compliance. (p = 0.223)

Endocrine complications were significantly associated with compliance. (p = 0.015)

TranQOL is not significantly correlated to the compliance. (p = 0.352)