Study selection
Our search identified 167 reports through database searches along with 3 additional reports identified through other resources. A total of 117 reports remained after removal of duplicates. We discarded 105 reports at the initial screening of the titles and abstracts because these clearly did not meet the eligibility criteria. We retrieved and assessed the full text of 12 reports. We excluded 3 reports of non-randomized studies. We included 9 reports of 3 studies. [15–17] Fig. 1 shows the study selection process. We did not identify any ongoing trial.
Study characteristics
Included studies
We summarized the characteristics of the included studies (country, participants, interventions, outcomes, study design, sample size, follow-up period) in Table 1.
Table 1
Characteristics of included studies
Study ID
(Trial registration)
|
Study design
|
Number randomized
|
Age of included women
|
Trial arms
|
Duration of treatment
|
Outcomes reported
|
Country
|
Burke 2018
NCT02293694
|
Open-label, parallel group, randomized clinical trial
|
731
|
18–40
|
Participants were randomized in a 1:1 ratio to self- or clinician administered subcutaneously DMPA 104 mg
|
12 months
|
continuation, satisfaction, failure (unintended pregnancy), side effects
|
Malawi
|
Kohn 2018
NCT02509767
|
Multicenter, open label, randomized parallel group clinical trial
|
401
|
15–44
|
Participants were randomized in a 1:1 ratio to self- or clinician administered subcutaneously DMPA 104 mg
|
12 months
|
continuation, satisfaction, failure (unintended pregnancy), side effects
|
USA
|
Beasley 2014
NCT01019369
|
Open label, parallel group, randomized clinical trial
|
132
|
18 or greater
|
Participants were randomized in a 2:1 ratio to self- or clinician administered subcutaneously DMPA 104 mg
|
12 months
|
continuation, satisfaction, side effects
|
USA
|
Methods and setting
We included three RCTs. The three trials included one multi-center trial in USA [15] and two single-site studies in USA [17] and Malawi [16].
Participants
Studies included a total of 1264 participants who were randomized to self-administration (651 women) versus a provider administration (613 women). All studies included women, in their reproductive age, receiving DMPA-SC for contraception.
Interventions
The three included studies randomized participants to receive self-administered or provider-administered DMPA-SC. The duration of follow-up was 12 months.
Outcomes
All included trials reported continuation of injectable contraception at 12 months as patient reported. [15–17] Only one study verified DMPA use by measuring trough MPA levels in blood. [15] Two studies reported failure (unintended pregnancy) and satisfaction [16, 17], two studies reported other (non-serious) adverse events [15, 17], and three studies reported serious adverse events, if any. [15–17]
Risk of bias within studies
We presented data on risk of bias of each study in Fig. 2 and Fig. 3. We made an outcome level assessment for detection bias since the lack of blinding may introduce bias in the measurement of women reporting of satisfaction. We judged the studies to be at high risk of performance bias due to the lack of blinding. The lack of blinding coupled with fixed block size is a potential source of selection bias in two of the included studies. [15, 17] Details and justifications for our judgements are provided in supplementary file 1.
Results of individual studies and Synthesis of results
Continuation of contraceptive use for 12 months was reported by the included RCTs (3 studies, 1261 women).
Self-administration, compared to provider-administration, improved continuation of contraceptive use (RR 1.3495 [1.0953; 1.6626]; P = 0.0049); moderate-certainty evidence), although there was substantial heterogeneity (Tau2 = 0.0239; I2 = 71.4% [3.1%; 91.6%]; P = 0.0301). We performed a sensitivity analysis using the fixed effect model that returned a Risk Ratio (M-H, Fixed, 95% CI) of 1.4401 [1.3023; 1.5924], P < 0.0001 (Fig. 4). Further, we investigated the source of heterogeneity using the pre-specified subgroup analysis.
For the subgroup analysis HIC vs LMIC, the test for subgroup differences was significant (Chi² = 5.71, df = 1, p = 0.0168). In HIC (2 studies, 530 women), the Risk Ratio (M-H, random, 95% CI) was 1.22 [1.04, 1.43] (very low certainty evidence). The NNT-b is 10 (95% CI, 5 to 53). In LMIC (1 study, 731 women), the Risk Ratio (M-H, random, 95% CI) was 1.59 [1.40, 1.81] (low certainty evidence), The NNT-b is 4 (95% CI, 3 to 5).
For the subgroup analysis by the type of care provider (community health worker vs clinic-based provider), the test for subgroup differences was not significant (Chi² = 0.05, df = 1 (P = 0.83), I² = 0%).
We also carried out a sensitivity analysis to assess the impact of attrition on the outcome of continuation, showing no change in the estimate of the effect.
Satisfaction at 12 months was reported by two studies.
In HIC (1 study, 398 women), Risk Ratio (M-H, Fixed, 95% CI) was 0.95 [0.84, 1.07] (very low certainty evidence). In LMIC (1 study, 731 women), Risk Ratio (M-H, Fixed, 95% CI) was 1.83 [1.61 to 2.07] (low certainty evidence). We did not pool the studies because there was substantial heterogeneity (Tau² = 0.22; Chi² = 55.34, df = 1 (P < 0.00001); I² = 98%). Test for subgroup differences for HIC vs LMIC: Chi² = 53.13, df = 1 (P < 0.00001), I² = 98.1%). We also carried out a sensitivity analysis to assess the impact of attrition on the outcome of satisfaction, showing no change in the estimate of the effect.
Contraceptive failure (unintended pregnancy) was reported in two studies (1129 women).
Risk Ratio (M-H, Fixed, 95% CI) was 0.47 [0.13, 1.67] (very low certainty evidence.
Only one woman reported serious adverse events in the three included trials (1261 women).
Risk Ratio (M-H, Fixed, 95% CI) was 0.34 [0.01, 8.22] (very low certainty evidence). These serious adverse events were menorrhagia and anemia requiring hospital admission) reported by one woman in the provider-administered group and resolved without sequelae.
Other adverse events were reported in two trials (863 women) with a Risk Ratio (M-H, Fixed, 95% CI) of 0.59 [0.28, 1.28] (very low certainty evidence). The other side effects included injection site pain or irritation, nausea, vomiting, irregular uterine bleeding, headaches, amenorrhea, decreased libido, and weight changes. All these non-serious adverse events did not require hospital treatment.
Details of GRADE summary of findings table all outcomes is shown in Table 2.
Table 2: Self-administration compared to provider-administered for DMPA-SC to improve contraceptive outcomes
Patient or population: women using DMPA-SC for contraception
Setting: Outpatient
Intervention: Self-administration
Comparison: provider-administered
Outcomes$
|
№ of participants (studies)
|
Certainty of the evidence (GRADE)
|
Relative effect (95% CI)
|
Anticipated absolute effects
|
Risk with provider-administered
|
Risk difference with Self-administration
|
Continuation: All studies
|
1261 (3 RCTs)
|
⨁⨁⨁◯ MODERATE a,b
|
RR 1.35 (1.10 to 1.66)
|
460 per 1,000
|
161 more per 1,000 (46 more to 304 more)
|
Continuation – LMIC
|
731 (1 RCT)
|
⨁⨁◯◯ LOW b,c
|
RR 1.59 (1.40 to 1.81)
|
458 per 1,000
|
270 more per 1,000 (183 more to 371 more)
|
Continuation – HIC
|
530 (2 RCTs)
|
⨁◯◯◯ VERY LOW a,b,d
|
RR 1.22 (1.04 to 1.43)
|
463 per 1,000
|
102 more per 1,000 (19 more to 199 more)
|
Satisfaction – LMIC
|
731 (1 RCT)
|
⨁⨁◯◯ LOW b,c,e
|
RR 1.83 (1.61 to 2.07)
|
447 per 1,000
|
371 more per 1,000 (273 more to 478 more)
|
Satisfaction – HIC
|
398 (1 RCT)
|
⨁◯◯◯ VERY LOW a,b,c,e
|
RR 0.95 (0.84 to 1.07)
|
730 per 1,000
|
37 fewer per 1,000 (117 fewer to 51 more)
|
Pregnancy
|
1129 (2 RCTs)
|
⨁◯◯◯ VERY LOW a,b,d,f
|
RR 0.47 (0.13 to 1.67)
|
12 per 1,000
|
7 fewer per 1,000 (11 fewer to 8 more)
|
Serious Adverse events
|
1261 (3 RCTs)
|
⨁◯◯◯ VERY LOW a,b,d,f,g
|
RR 0.34 (0.01 to 8.22)
|
2 per 1,000
|
1 fewer per 1,000 (2 fewer to 12 more)
|
Other Adverse events
|
863 (2 RCTs)
|
⨁◯◯◯ VERY LOW a,b,d,f,g
|
RR 0.59 (0.28 to 1.28)
|
41 per 1,000
|
17 fewer per 1,000 (30 fewer to 12 more)
|
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
$ Outcomes assessed with: Patient reported. Follow up: mean 12 months
CI: Confidence interval; RR: Risk ratio
GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
Explanations
- Two studies had a potential source of selection bias related to the specific study design used: no blinding with a fixed block size.
- Neither participants nor study staff were masked due to the nature of interventions. We judge that the performance is likely to be influenced by lack of blinding.
- Data from one study and optimal information size not fulfilled
- The number of participants does not reach the optimal information size.
- No blinding of outcome assessor. We judge that the outcome measurement is likely to be influenced by lack of blinding.
- Wide confidence interval encompassing large effect size and no effect
- Data from studies with rare events.