TABLE 1.
Characteristics of the included studies
| Study and year | Study design | Follow up (SD)[range] | Participants in group (n) | Outcomes | Notes |
|---|---|---|---|---|---|
| Intervention: all advanced treatments | |||||
| Dafsari 2019 | Prospective, non‐randomized, open‐label multicenter, real‐life cohort study of CSAI, DBS, LCIG | 6 mo | 39(CSAI)/101 (DBS)/33(LCIG) | QoL, adverse events | Large group of real‐life cohort study, therefore not comparable groups at baseline |
| Intervention: DBS original RCTs (additional articles of same RCT) | |||||
| Deuschl 2006 (Witt 2008, Daniels 2011, Witt 2011) | Randomized (paired), controlled, unblinded trial DBS vs. BMT | 6 mo | 78 (DBS)/78 (BMT) | QoL, ADL ON/OFF time, adverse events | |
| Schuepbach 2007 (Lhommee 2018, Schuepbach 2019) | Randomized (matched pairs), controlled, unblinded trial (pilot study) | 18 mo | 10 (DBS)/10 (BMT) | QoL, ADL | Patients with shorter disease duration with motor fluctuations |
| Weaver 2009 (Weaver 2012, Rothlind 2015) |
Randomized, controlled, multicenter trial Blinded motor assessment stratification by study site and age |
6 mo | 121 (DBS)/134 (BMT) | ADL, ON/OFF time, adverse events | |
| Williams 2010 | Randomized (pairwise), unblinded trial | 1 y | 183(DBS)/183(BMT) | QoL, ADL, OFF time, adverse events | Over 1/3 used apomorphine as well, unclear if this was CSAI or injections |
| Schuepbach 2013 | Randomized, controlled, multicenter, unblinded trial | 24 mo | 124 (DBS)/127 (BMT) | QoL, ADL, ON/OFF time, adverse events | Patients with shorter disease duration with motor fluctuations |
| Intervention: LCIG original RCTs (additional articles of same RCT) | |||||
| Kurth 1993 | Double‐blinded, placebo‐controlled, cross‐over study, randomized in six different treatment schemes of LCIG vs. BMT | 4 d | 10 | ON/OFF time | LCIG (and placebo) through nasoduodenal tube |
| Nyholm 2005 (Isacson 2008) | Randomized, multicenter, cross‐over trial LCIG vs. BMT | 6 wk and 6 mo | 25 | QoL, ON/OFF time | Only 12 patients available for follow‐up data, LCIG through nasoduodenal tube |
| Olanow 2014 (Antonini 2016) | Randomized, multicenter, double‐blinded, placebo‐controlled trial of LCIG vs. BMT | 12 wk | 37 LCIG(+BMT)/34 placebo (+BMT) | QoL, ADL, ON/OFF time | Placebo group also had PEG‐J surgery |
| Intervention: LCIG non‐randomized studies/cohort studies (additional articles of same study) | |||||
| Antonini 2008 | Prospective, before−after, open‐label, multicenter study of LCIG | 2 y | 22 | QoL, ADL, adverse events | |
| Palhagen 2012/Palhagen 2016 | Prospective, open‐label, multicenter, cohort study of LCIG | 3 y | 77 (36 LCIG naïve patients) | QoL, ADL, adverse events | Large group already treated with LCIG, in our analysis only LCIG naïve population is taken |
| Fernandez 2013/Fernandez 2015 | Prospective, multicenter, before−after, open‐label study of LCIG | 54 wk | 354 | QoL, ADL, ON/OFF time, adverse events | Fernandez 2013 is interim analysis, Fernandez 2015 is final analysis |
| Zibetti 2013 | Prospective, open‐label, multicenter, cohort study of LCIG | 3 y | 25 | QoL, ADL, adverse events | |
| Caceres‐Redondo 2014 | Prospective, before−after, open‐label study of LCIG | 32.2 ± 12.4 mo | 29 | QoL, ADL, adverse events | |
| Antonini 2015/Antonini 2017 | Prospective, multicenter, before−after, open‐label study of LCIG | 24 mo | 375 (225 prospective cohort) | QoL, ADL, ON/OFF time, adverse events | Includes retrospective cohort and prospective cohort. We only included the prospective cohort |
| Bohlega 2015 | Prospective, before−after, open‐label study of LCIG | 48.5 ± 23.2 mo | 20 | QoL, adverse events | |
| Martinez‐Martin 2015 | Prospective, non‐randomized, comparative, open‐label study CSAI vs. LCIG (data for before−after study of CSAI and LCIG) | 6 mo | 44 | QoL, adverse events | Stated as a comparative trial CSAI vs. LCIG, however separate before−after data are presented |
| Slevin 2015 | Open‐label, multicenter, extension study of the RCT (Olanow 2014) of LCIG vs. BMT | 52 wk | 62 (29 naïve) | QoL, ADL, ON/OFF time, adverse events | Patients in BMT group of RCT were offered to switch to LCIG and were analyzed in this study as naive LCIG group alongside the continuous LCIG treatment group (and a combined analysis as well) |
| Catalan 2018 | Prospective, multicenter, before−after, open‐label study of LCIG | 6 mo | 62 | ADL, ON/OFF time | |
| Ciurleo 2018 | Prospective, before−after, open‐label study of LCIG | 6 mo | 12 | QoL | |
| Vijiaratnam 2018 | Prospective, before−after, open‐label study of LCIG | 6 mo | 25 | QoL, ADL, adverse events | |
| Intervention: CSAI RCT | |||||
| Katzenschlager 2018 | Randomized, placebo‐controlled, double‐blind, multicenter trial of CSAI vs. BMT | 12 wk | 53(CSAI)/54(BMT) | QoL, ADL, ON/OFF time, adverse events | Only RCT with relevant outcomes for our study |
| Intervention: CSAI non‐randomized studies/cohort studies (additional articles of same study) | |||||
| Stibe 1988 | Prospective, before−after, open‐label study with 2 groups (CSAI and apomorphine injections) | 8 mo [1–15] | 11 CSAI | ON/OFF time | In our analysis only CSAI included |
| Pietz 1998 | Prospective, before−after, open‐label study with 2 groups (CSAI and apomorphine injections) | 20.2 mo (54.0 mo) | 25 CSAI | ADL, OFF time | In our analysis only CSAI included |
| Kanovsky 2002 | Prospective, before−after, open‐label study | 2 y | 12 CSAI | ON/OFF time, adverse events | |
| Di Rosa 2003/Morgante 2004 | Non‐randomized, open‐label, blinded‐rater, parallel‐group trial CSAI vs. BMT | 1 y/2 y | 12 (CSAI)/18 (BMT) | OFF time, adverse events | The two articles describe the same study population but different follow‐up. An important exclusion criterion was age above 65 y |
| Katzenschlager 2005 | Prospective, 2 centers before−‐after study, blinded rating of video assessments | 6 mo | 12 CSAI | ON/OFF time, adverse events | |
| De Gaspari 2006/Antonini 2011 | Prospective, before−after, open‐label study of CSAI (or DBS patients) |
1 y 5 y |
12 CSAI | OFF time | Antonini study not included for analysis as only 2/13 patients reached 5‐y follow‐up |
| Martinez‐Martin 2011 | Non‐randomized, open‐label, parallel group trial CSAI vs. BMT | 12.5 mo (11.5 mo) | 17 (CSAI)/17 (BMT) | QoL | No accurate control group, no comparable groups at baseline |
| Martinez‐Martin 2015 | Prospective, non‐randomized, comparative, open‐label study CSAI vs. LCIG (data for before−after study of CSAI and LCIG) | 6 mo | 43 CSAI | QoL, adverse events | Stated as a comparative trial CSAI vs. LCIG, however separate before−after data are presented |
Abbreviations: SD, standard deviation; CSAI, continuous subcutaneous apomorphine infusion; DBS, deep brain stimulation; LCIG, levodopa‐carbidopa intestinal gel; mo, month; QoL, quality of life; RCT, randomized controlled trial; BMT, best medical treatment; ADL, activities of daily living; mo; months; ON/OFF time: duration of on time and duration of OFF time.