There have been a number of clinical trials in glaucoma research published in the past two decades. Most of these trials were designed to evaluate very specific issues in selected populations placing them in the explanatory end of the pragmatic-explanatory continuum. The purpose of this study was to assess the level of pragmatism of published randomized controlled trials in glaucoma.
Methods
A PubMed search using ‘glaucoma’ from 1995 to 2022 and randomized controlled trial (RCT) article type was done. Each study was assessed by three independent examiners using the Pragmatic-Explanatory Continuum Indicator Summary version 2 (PRECIS-2) toolkit. Scores were calculated for each study to determine the level of pragmatism. A summed score ≥36 was indicative of a very pragmatic study.
Results
Thirty-two different articles were included in the analysis. These papers represented 13 different landmark trials. The median PRECIS-2 score was 32 (range, 25 for the Early Manifest Glaucoma Trial (EMGT) to 34 to the Collaborative Normal Tension Glaucoma Study (CNTGS) and the Ocular Hypertension Treatment Study). The Treatment of Advanced Glaucoma Study (TAGS), was considered very pragmatic and scored 33 points.
Conclusion
Despite the number of RCTs in glaucoma, there is still a need for more pragmatic studies.
AlRyalatSAAbukahelAElubousKA. Randomized controlled trials in ophthalmology: a bibliometric study. F1000Res2019; 8: 1718.
2.
MerciecaK. Pivotal studies in glaucoma in the past 10 years. Ophthalmologie2022; 119(Suppl 2): 137–139.
3.
SchwartzDLellouchJ. Explanatory and pragmatic attitudes in therapeutical trials. J Chronic Dis1967; 20: 637–648.
4.
Dal-RéRJaniaudPIoannidisJPA. Real-world evidence: how pragmatic are randomized controlled trials labeled as pragmatic?BMC Med2018; 16: 49.
5.
LoudonKTreweekSSullivanF, et al.The PRECIS-2 tool: designing trials that are fit for purpose. Br Med J2015; 350: h2147.
6.
SajobiTTLiGAwosogaO, et al.A comparison of meta-analytic methods for synthesizing evidence from explanatory and pragmatic trials. Syst Rev2018; 7: 19.
7.
JordanAEPerlmanDCSmithDJ, et al.Use of the PRECIS-II instrument to categorize reports along the efficacy-effectiveness spectrum in a hepatitis C virus care continuum systematic review and meta-analysis. J Clin Epidemiol2018; 93: 66–75.
8.
KooTKLiMY. A guideline of selecting and reporting intraclass correlation coefficients for reliability research. J Chiropr Med2016; 15: 155–163.
9.
EdererFGaasterlandDESullivanEK, et al.The advanced glaucoma intervention study (AGIS): 1. Study design and methods and baseline characteristics of study patients. Control Clin Trials1994; 15: 299–325.
10.
EdererFGaasterlandDADallyLG, et al.The advanced glaucoma intervention study (AGIS):13. Comparison of treatment outcomes within race: 10-year results. Ophthalmol2004; 111: 651–664.
11.
Collaborative normal-tension glaucoma study group. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am J Ophthalmol1998; 126: 487–497.
12.
Collaborative normal-tension glaucoma study group.The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Am J Ophthalmol1998; 126: 498–505.
13.
AndersonDRDranceSMSchulzerM, et al.Natural history of normal-tension glaucoma. Ophthalmol2001; 108: 247–253.
14.
MuschDCLichterPRGuireKE,et al.The collaborative initial glaucoma treatment study: study design, methods, and baseline characteristics of enrolled patients. Ophthalmol1999; 106: 653–662.
15.
LichterPRMuschDCGillespieBW, et al.Interim clinical outcomes in the collaborative initial glaucoma treatment study comparing initial treatment randomized to medications or surgery. Ophthalmol2001; 108: 1943–1953.
HeijlALeskeMCBengtssonB, et al.Reduction of intraocular pressure and glaucoma progression: results from the early manifest glaucoma trial. Arch Ophthalmol2002; 120: 1268–1279.
18.
KassMAHeuerDKHigginbothamEJ, et al.The ocular hypertension treatment study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol2002; 120: 701–713.
19.
GordonMOBeiserJABrandtJD, et al.The ocular hypertension treatment study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol2002; 120: 714–720.
20.
KassMAGordonMOGaoF, et al.Delaying treatment of ocular hypertension: the ocular hypertension treatment study. Arch Ophthalmol2010; 128: 276–287.
21.
MigliorSZeyenTPfeifferN, et al.The European glaucoma prevention study design and baseline description of the participants. Ophthalmol2002; 109: 1612–1621.
22.
MigliorSZeyenTPfeifferN, et al.Results of the European glaucoma prevention study. Ophthalmol2005; 112: 366–375.
23.
GeddeSJSchiffmanJCFeuerWJ, et al.The tube versus trabeculectomy study: design and baseline characteristics of study patients. Am J Ophthalmol2005; 140: 275–287.
24.
GeddeSJSchiffmanJCFeuerWJ, et al.Treatment outcomes in the tube versus trabeculectomy study after one year of follow-up. Am J Ophthalmol2007; 143: 9–22.
25.
GeddeSJSchiffmanJCFeuerWJ, et al.Treatment outcomes in the tube versus trabeculectomy (TVT) study after five years of follow-up. Am J Ophthalmol2012; 153: 789–803. e2.
26.
ChristakisPGTsaiJCZurakowskiD, et al.The Ahmed versus Baerveldt study: design, baseline patient characteristics, and intraoperative complications. Ophthalmol2011; 118: 2172–2179.
27.
ChristakisPGKalenakJWZurakowskiD, et al.The Ahmed versus Baerveldt study: one-year treatment outcomes. Ophthalmol2011; 118: 2180–2189.
28.
ChristakisPGTsaiJCKalenakJW, et al.The Ahmed versus Baerveldt study: three-year treatment outcomes. Ophthalmol2013; 120: 2232–2240.
29.
Azuara-BlancoABurrJMCochranC, et al.The effectiveness of early lens extraction with intraocular lens implantation for the treatment of primary angle-closure glaucoma (EAGLE): study protocol for a randomized controlled trial. Trials2011; 12: 133.
30.
Azuara-BlancoABurrJRamsayC, et al.Effectiveness of early lens extraction for the treatment of primary angle-closure glaucoma (EAGLE): a randomised controlled trial. Lancet2016; 388: 1389–1397.
31.
GazzardGKonstantakopoulouEGarway-HeathD, et al.Laser in glaucoma and ocular hypertension (LiGHT) trial. A multicentre, randomised controlled trial: design and methodology. Br J Ophthalmol2018; 102: 593–598.
32.
KonstantakopoulouEGazzardGVickerstaffV, et al.The Laser in glaucoma and ocular hypertension (LiGHT) trial. A multicentre randomised controlled trial: baseline patient characteristics. Br J Ophthalmol2018; 102: 599–603.
33.
GargAVickerstaffVNathwaniN, et al.Primary selective Laser trabeculoplasty for open-angle glaucoma and ocular hypertension: clinical outcomes, predictors of success, and safety from the Laser in glaucoma and ocular hypertension trial. Ophthalmol2019; 126: 1238–1248.
34.
GeddeSJFeuerWJShiW, et al.Treatment outcomes in the primary tube versus trabeculectomy study after 1 year of follow-up. Ophthalmol2018; 125: 650–663.
35.
GeddeSJChenPPHeuerDK, et al.The primary tube versus trabeculectomy study: methodology of a multicenter randomized clinical trial comparing tube shunt surgery and trabeculectomy with mitomycin C. Ophthalmol2018; 125: 774–781.
36.
GeddeSJFeuerWJLimKS, et al.Treatment outcomes in the primary tube versus trabeculectomy study after 3 years of follow-up. Ophthalmol2020; 127: 333–345.
37.
KingAJFernieGAzuara-BlancoA, et al.Treatment of advanced glaucoma study: a multicentre randomised controlled trial comparing primary medical treatment with primary trabeculectomy for people with newly diagnosed advanced glaucoma—study protocol. Brit J Ophthalmol2018; 102: 922–928.
38.
KingAJHudsonJFernieG, et al.Primary trabeculectomy for advanced glaucoma: pragmatic multicentre randomised controlled trial (TAGS). Br Med J2021; 373: n1014.
39.
JiangYFriedmanDSHeM, et al.Design and methodology of a randomized controlled trial of laser iridotomy for the prevention of angle closure in southern China: the Zhongshan angle closure prevention trial. Ophthalmic Epidemiol2010; 17: 321–332.
40.
HeMJiangYHuangS, et al.Laser peripheral iridotomy for the prevention of angle closure: a single-centre, randomised controlled trial. Lancet2019; 393: 1609–1618.
41.
FordINorrieJ. Pragmatic trials. N Engl J Med2016; 375: 454–463.
42.
Dal-RéR. The PRECIS-2 tool seems not to be useful to discriminate the degree of pragmatism of medicine masked trials from that of open-label trials. Eur J Clin Pharmacol2021; 77: 539–546.
43.
ZwarensteinMThorpeKTreweekS,et al.PRECIS-2 for retrospective assessment of RCTs in systematic reviews. J Clin Epidemiol2020; 126: 202–206.
