ライフサイエンスコーパス: efficacy

1 t, differentiation, migration, and treatment efficacy.

2 mal effect of Au@Rh-ICG-CM also improves PDT efficacy.

3 iagnosis, resistance patterns, and treatment efficacy.

4 l ND diseases are discussed to evaluate drug efficacy.

5 -19) despite a paucity of evidence regarding efficacy.

6 which was not observed during antipsychotic efficacy.

7 ht serve as an early predictor of CAR T cell efficacy.

8 high levels of pre- and post-CHMI protective efficacy.

9 ChAd-S alone showed no efficacy.

10 mg/m2 IV in the first 2 cycles, with similar efficacy.

11 sting prolonged mammary exposure may improve efficacy.

12 inciple data for its blood pressure-lowering efficacy.

13 on, leading to enhancement of BRAF inhibitor efficacy.

14 s a key factor determining their potency and efficacy.

15 ures has changed minimally despite poor drug efficacy.

16 ty appears to be predictive of pembrolizumab efficacy.

17 harness them in support of superior clinical efficacy.

18 sunlight, which limits their persistence and efficacy.

19 se variables can markedly affect therapeutic efficacy.

20 imary analysis groups: safety and hemostatic efficacy.

21 fluence RhCMV/SIV vaccine immunogenicity and efficacy.

22 nd our approach to optimizing for safety and efficacy.

23 l migration from lymph nodes for therapeutic efficacy.

24 y are either strain specific or have limited efficacy.

25 a modified BoNT/B with improved therapeutic efficacy.

26 reatment and thus were evaluable for 12-week efficacy.

27 t upward social comparison reduces political efficacy(4).

28 Dalbavancin does not offer an economic or efficacy advantage.

29 QACs) had significant chain-length dependent efficacy against A. castellanii trophozoites, the latter

30 xhibited antimicrobial activity, with higher efficacy against Gram-positive strains than Gram-negativ

31 Secondly, in vivo, we have investigated its efficacy against infectious bronchitis using a broiler i

32 ormin enhances immunogenicity and protective efficacy against M. tuberculosis challenge.

33 etween populations may contribute to reduced efficacy against severe rotavirus disease.

34 portant determinants of CD8+ T cell-mediated efficacy against SIV.

35 les (uPtDs NPs) and tested their therapeutic efficacy against TNBC metastasis.

36 a naturally occurring HDP, and tested their efficacy against VEEV.

37 istered with remdesivir, did not demonstrate efficacy among hospitalized patients who had Covid-19 wi

38 Efficacy analyses were performed by applying RECIST 1.1

39 1 patients were included in the per-protocol efficacy analyses.

40 treat population was used for the safety and efficacy analyses; all analyses, and their timings, were

41 dder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were inclu

42 At the time of the primary efficacy analysis (ie, when all participants had complet

43 32.3), 57% of the 60 patients in the primary efficacy analysis were in remission.

44 Brazil) were included in the interim primary efficacy analysis.

45 tinib, selpercatinib) demonstrating improved efficacy and a more favorable toxicity profile are poise

46 g strategies in order to improve the safety, efficacy and applicability of this therapeutic modality.

47 s are noninferior to warfarin with regard to efficacy and are associated with lower rates of bleeding

48 iotics that would increase its antimicrobial efficacy and at the same time reduce the development of

49 MIGS represent an evolving field, and the efficacy and complications of each procedure should be c

50 We used a mathematical model to predict the efficacy and effectiveness of different dosing regimens.

51 81G has been associated with reduced IPTp-SP efficacy and enhanced morbidity in SP recipients.

52 omous AI, and understand its design, safety, efficacy and equity, validation, and liability, as well

53 ted patient exhibited highest levels of self-efficacy and exercise.

54 the role of perforin in anti-CD19 CAR T cell efficacy and HLH-like toxicities in a syngeneic murine m

55 is ongoing for long-term outcomes, including efficacy and long-term safety.

56 Efficacy and Mechanism Evaluation (EME) Programme, an MR

57 d contribute to the ongoing debate about the efficacy and mechanism(s) of action of "TTFields" by bet

58 and obesity but have limited weight-lowering efficacy and minimal insulin sensitizing action.

59 e present preclinical data on domatinostat's efficacy and mode of action in MCC.

60 1 inhibitors demonstrated impressive in vivo efficacy and overall promising pharmacokinetic propertie

61 topical instillation limits its therapeutic efficacy and poses a challenge for potential patient com

62 Th2 and Th17 differentiation and exert high efficacy and potency to help Env trimer humoral immune r

63 Consistently Sym004 efficacy and potentiation of cisplatin responses correla

64 Their therapeutic efficacy and preliminary toxicology profiles were assess

65 inhibition of TRIM37 increases chemotherapy efficacy and reduces metastasis risk in patients with TN

66 s of drug candidates are important for their efficacy and safety as therapeutics.

67 the upstream strategy on the combination of efficacy and safety events (net clinical benefit).

68 We aimed to assess the efficacy and safety of atezolizumab (anti-PD-L1) alone a

69 IMpassion031 compared efficacy and safety of atezolizumab versus placebo combi

70 Evidence supports the efficacy and safety of both in-office and facility-based

71 oderate to Severe Plaque Psoriasis], and -3 [Efficacy and Safety of Brodalumab Compared With Placebo

72 objective of this review was to compare the efficacy and safety of conservative surgery with or with

73 In the United States, the efficacy and safety of convalescent plasma for treating

74 omplex, with limited guidance on comparative efficacy and safety of different treatments, leading to

75 n randomized clinical trials to evaluate the efficacy and safety of DOACs in patients with CAT.

76 We aimed to measure the efficacy and safety of gabapentin in women with chronic

77 The phase 3 ASPEN study compared the efficacy and safety of ibrutinib, a first-generation BTK

78 We aimed to evaluate the efficacy and safety of ixekizumab, an IL-17 inhibitor, i

79 irm results on long-term outcome focusing on efficacy and safety of long-term use of rituximab mainte

80 Herein, the 12-month efficacy and safety of netarsudil/latanoprost FDC are re

81 larger trials are necessary to evaluate the efficacy and safety of sodium phenylbutyrate-taurursodio

82 We assessed the efficacy and safety of ticagrelor versus prasugrel in a

83 ADVANCE compared the efficacy and safety of two antiretroviral first-line com

84 This Phase 2 clinical study evaluated the efficacy and safety of VT-1161 versus fluconazole in sub

85 this retrospective study was to compare the efficacy and safety profile of a single XEN-microstent i

86 However, its efficacy and safety remain unclear.

87 l study differs from a traditional phase III efficacy and safety study in the development of a novel

88 the brolucizumab q12-week regimen maintains efficacy and safety while reducing treatment burden asso

89 This study demonstrates high efficacy and safety with contemporary S-ICD devices and

90 2 weeks, as primary surrogate end points of efficacy and safety, respectively.

91 s were to assess the safety and evaluate the efficacy and stability of biochemical and functional rec

92 ing technologies are expected to enhance the efficacy and tolerability of DBS.

93 le to maintain BR dose intensity may improve efficacy and tolerability of VEN + BR, while VEN + R dat

94 nfusion products contributes to variation in efficacy and toxicity after axi-cel therapy in LBCL, and

95 perties of antibodies are critical for their efficacy and toxicity.

96 mplete, the therapeutic options have limited efficacy, and are often fraught with risks.

97 Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommen

98 Whether this efficacy, and the rates of toxicity, would be consistent

99 ampered by issues such as toxicity, variable efficacy, and unsuitable dosing options.

100 ent) was compared in vitro and their vaccine efficacy (antigen-specific antibody responses and IFN-ga

101 CI, 1.95, 4.29, P = .001), and genetics self-efficacy (aOR, 2.38; 95% CI, 1.54, 3.67, P = .001) were

102 Safety and efficacy are summarized for the initial 48 weeks of the

103 -1 inhibitor pembrolizumab have demonstrated efficacy as monotherapy and are playing an increasingly

104 Daratumumab showed encouraging efficacy as monotherapy in patients with heavily pretrea

105 The coprimary outcomes of the trial were efficacy, as measured by the number of cases of symptoma

106 latin sensitivity and serving as a treatment efficacy biomarker.

107 closely agree with measured drug combination efficacies both in vitro (Pearson's correlation = 0.93 w

108 irst 11 months, and the secondary endpoints (efficacy by baseline serostatus, serotype, hospitalised

109 nologies to further improve the gene therapy efficacy by prolonging the release of nucleic acid drug

110 drogel network and long lasting photothermal efficacies can be maintained for cancer therapy.

111 atment under the Animal Efficacy Rule, where efficacy can be demonstrated in 1 or more well-character

112 T cells in the blood, evidence of treatment efficacy can only be found in the allograft itself, mean

113 1 or PfLSAP2 was shown to improve protective efficacy compared to vaccination with each single-antige

114 nase inhibitors have the potential for broad efficacy, convenience and tissue penetrance, and thus of

115 ealth care: skills transfer, increasing self-efficacy, coordination, knowledge transfer, linking to a

116 is study was to provide long-term safety and efficacy data for evolocumab in patients with homozygous

117 f these associations are unexpected based on efficacy data or evidence-based guidelines.

118 vance to clinical trials without preclinical efficacy data, due primarily to a paucity of relevant an

119 ar benefit (2.3% versus 1.4% for the primary efficacy end point at 3 years, Gail-Simon qualitative P(

120 red by the clinical composite score (primary efficacy end point), quality of life, LV structural remo

121 The primary efficacy end point, percentage change in total plaque vo

122 Here we report the key secondary efficacy endpoint of the proportion of participants who

123 The primary efficacy endpoint was the mean rate of change in GA over

124 on-inferiority of the groups for the primary efficacy endpoint.

125 Binding affinity (K(d)), Receptor activation Efficacy (epsilon), and constitutive activity (epsilon(R

126 ADAPT protocol, was estimated using subgroup efficacy estimates from the preexposure prophylaxis init

127 41 (77%; 95% CI 64-88) of 53 patients in the efficacy-evaluable population had an objective response.

128 34; 25-59) and 65% (22 of 34; 47-80) in the efficacy-evaluable population.

129 Efficacy evaluation through human trials is crucial for

130 n comparing predicted efficacies to measured efficacies for >5000 combinations) and in a systematical

131 PrEP efficacy for covered sex acts, as defined in the HPTN 06

132 Treatment efficacy for diabetes mellitus is largely determined by

133 esponse curves confirmed greater (P = 0.003) efficacy for G:G homozygotes (%AUC difference = 43.7, 95

134 Halving the efficacy for partially covered acts decreases effectiven

135 BT, to determine feasibility and preliminary efficacy for preventing chronic pain and long-term opioi

136 Vaccine efficacy for vaccinated girls, HE for unvaccinated girls

137 ease was found in eye drop instillation self-efficacy from an average score of 2.6 (standard deviatio

138 ) are widely used screening tools, but their efficacy has not yet been compared in Mexican patients.

139 c T cell engagers have demonstrated clinical efficacy; however, their use can be accompanied by sever

140 y, the strongest association with esketamine efficacy identified in the polygenic score analysis was

141 Discontinuation was due to lack or loss of efficacy in 74 patients, adverse event in 34 patients, a

142 cts, we tested PEAMOtecan as monotherapy for efficacy in a mouse orthotopic glioma model.

143 lease of GRFT, and to examine its safety and efficacy in a murine model of lethal HSV-2 infection.

144 Herein, we report proof-of-concept in vivo efficacy in an streptozotocin-induced vascular leakage m

145 f 53BP1 deficiency, such as diminished PARPi efficacy in BRCA1-deficient cells and altered repair of

146 1895344, which exhibited strong monotherapy efficacy in cancer xenograft models that carry certain D

147 l miltefosine in monotherapy has proven high efficacy in CL caused by L. braziliensis with a cure rat

148 COMBAT can predict antibiotic efficacy in clinical isolates for quinolones from drug a

149 he observed effectiveness is consistent with efficacy in clinical trials and supports current recomme

150 mbinant IL-18 previously did not demonstrate efficacy in clinical trials(3).

151 hycA, dsrB, and bolA potentiated carbapenem efficacy in CRE E. coli, whereas inhibition of the genes

152 rectly in unbiased evaluation of synergistic efficacy in drug combinations using probabilistic models

153 es with age, Shingrix protection retains its efficacy in elderly subjects (individuals 80 years of ag

154 ising approach to treat cancer, however, its efficacy in highly malignant brain-tumors, glioblastomas

155 ether small animal models accurately predict efficacy in humans.

156 imilar efficacy overall, and possibly better efficacy in more severe disease warrant further study.

157 nti-PD1 therapies have demonstrated clinical efficacy in multiple cancers.

158 cross-talk shape tumor immunity and therapy efficacy in patients with cancer.

159 bility of eliciting a saccade depends on its efficacy in reducing the foveal offset.

160 BRAF inhibitors have shown efficacy in several cancers; however, most patients even

161 sed combination therapies have shown reduced efficacy in some countries in the GMS at some point.

162 lung adenocarcinoma, EGFR-TKIs show enhanced efficacy in spheroid cultures.

163 ere found to be the key factors for the drug efficacy in the 3D tumor model, governed by the Cu(+2)/C

164 igh target specificity but displayed reduced efficacy in the presence of serum IgG.

165 toms as a prognostic indicator of prazosin's efficacy in the treatment of AUD.

166 stance mechanisms have demonstrated clinical efficacy in these regards, thus highlighting the utility

167 Efficacy index which equals post-operative mean of uncor

168 We show that low intrinsic efficacy is a major determinant of these distortions, an

169 Diagnostic efficacy is evaluated by a panel of hematologists perfor

170 The reduced efficacy is reminiscent of multisubunit protein ion chan

171 xposure, and therefore compromise prevention efficacy, is unknown.

172 ut current treatment options provide limited efficacy, leaving as many as one-third of patients with

173 might provide better diagnostic accuracy and efficacy levels than PBMCs.

174 There is evidence that its analgesic efficacy might be modified by variants of the catechol-O

175 The efficacy of (18)F-rhPSMA-7 is similar to published data

176 and PET/MRI examinations to investigate the efficacy of (18)F-rhPSMA-7 PET for primary N-staging of

177 To evaluate the in vivo efficacy of (212)Pb-daratumumab, mice were engrafted sub

178 protein, and may contribute to the clinical efficacy of 5-AzadC.

179 accurately predicts life expectancy and the efficacy of a lifespan-extending intervention up to a ye

180 novel hypothesis that the immunotherapeutic efficacy of a microbial-based stimulus for innate immune

181 vity during lung infection and to assess the efficacy of a protease inhibitor therapy targeting neutr

182 We aimed to test the efficacy of ablating cardiac magnetic resonance (CMR)-de

183 We compare the efficacy of acalabrutinib with or without obinutuzumab a

184 tem cell (MSCs), we evaluated the safety and efficacy of an allogenic MSC-based intramammary therapy

185 thways that could be targeted to enhance the efficacy of an EBV-specific vaccine or treat severe EBV

186 This study evaluates the safety and efficacy of an intracameral combination of 2 mydriatics

187 veal that a dendronized polymer augments the efficacy of an oncolytic peptide (OP; KKWWKKWDipK) for i

188 ression of genes whose action diminishes the efficacy of anti-cancer drugs.

189 r study confirmed the potential differential efficacy of anti-vascular endothelial growth factor agen

190 ntrolled trials have compared the safety and efficacy of any integrase inhibitor to efavirenz when in

191 The long-term safety and efficacy of apomorphine sublingual film are currently be

192 We tested the efficacy of APTi with two gene families, the actin-depen

193 led trial was primarily aimed at testing the efficacy of ARP as compared with unassisted socket heali

194 ls and tumors were associated with decreased efficacy of atezolizumab in patients with mUC and metast

195 present study is to investigate the in vivo efficacy of auranofin (rheumatoid arthritis FDA-approved

196 e investigated the immunologic and virologic efficacy of baricitinib in a rhesus macaque model of SAR

197 .tb.) challenge model to test the protective efficacy of BCG-disA-OE versus wild-type BCG and measure

198 rspective: Clinical trial data show that the efficacy of birch pollen AIT is not only related to birc

199 The efficacy of blocking HBsAg and HDV production were 98.2

200 umor activities of phenformin to enhance the efficacy of BRAF-MAPK kinase-extracellular signal-regula

201 The aim of this study is to evaluate the efficacy of brain MRI without anesthesia in infants youn

202 Our understanding of the safety and efficacy of cannabis has been limited by decades of worl

203 romising therapeutic strategy to improve the efficacy of chemotherapy treatment.

204 lly enhanced under eCO(2), and challenge the efficacy of climate mitigation strategies that rely on u

205 to other antipsychotics, and whether greater efficacy of clozapine is dependent on the degree of trea

206 The overall diagnostic efficacy of combined GS and SoC approaches was 26 of 34

207 xt ZIKV outbreak might occur, evaluating the efficacy of conventional and novel intervention measures

208 model of SZ and can explain the lack of full efficacy of conventional antipsychotic medication on SZ

209 en to compensate for the reduced therapeutic efficacy of conventional chemotherapy.

210 cific antitumor effects, and can improve the efficacy of conventional therapeutic agents.

211 Putative mechanisms of suboptimal efficacy of DARA include downregulation of CD38 expressi

212 simple and inexpensive method to improve the efficacy of deltamethrin, the most active and most commo

213 infected subjects is an important measure of efficacy of drugs and vaccines.

214 nges and have great potential to improve the efficacy of DSF-based cancer therapy.

215 nce remains the key obstacle to the clinical efficacy of EGFR tyrosine kinase inhibitors (TKI).

216 Although the efficacy of exercises for primary convergence insufficie

217 in conjunction with fluoxetine restores the efficacy of fluoxetine actions on D1 receptor expression

218 We previously reported superior efficacy of fostemsavir versus placebo in the randomised

219 prior to challenge abrogated the protective efficacy of GCP-rCpa1 vaccine.

220 ar to the hypertrophic scar and keloids, the efficacy of glucorticoids (GC) for vocal fold injury is

221 has been structurally defined; however, the efficacy of h5B3.1 in vivo is unknown.

222 Here, we demonstrate the efficacy of ICT12035, in a number of 2D and 3D prolifera

223 he tumour microenvironment, reflected in the efficacy of immune checkpoint interventions, further pro

224 , the increasing evidence for the safety and efficacy of immunotherapies in the context of HIV and ca

225 emethylases in tumor cells contribute to the efficacy of immunotherapy and identify ALKBH5 as a poten

226 kinase 1/2 signaling; however, the clinical efficacy of inhibitors to this pathway is limited by res

227 y examined how O-GlcNAcylation modulates the efficacy of inhibitory neurotransmission.

228 Data on the safety and efficacy of IPT in pregnant women living with HIV (PWLHI

229 The goal of this work is to evaluate the efficacy of machine learning algorithms to cluster the p

230 The antiviral efficacy of many nucleoside analogues is strongly depend

231 Randomized clinical trials support the efficacy of MDMA in the treatment of PTSD and psilocybin

232 double-blind clinical trial to evaluate the efficacy of miltefosine combined with topical GM-CSF (M+

233 en limited until recently, and the antitumor efficacy of most cancer immunotherapies still needs to b

234 hat target women are required to bolster the efficacy of OAT in preventing HCV transmission.

235 d, controlled trials evaluating the clinical efficacy of PCCs in patients with factor Xa inhibitor-re

236 periodontal health in situations with waning efficacy of personal oral hygiene.

237 In Zintl phases and skutterudites, the efficacy of phase-boundary mapping is demonstrated throu

238 utilize NCT, these findings demonstrate the efficacy of polymersomes to deliver encapsulated payload

239 The efficacy of polypharmacy showed additivity when gentamic

240 Here we investigate the efficacy of remdesivir in a rhesus macaque model of SARS

241 e data presented here support testing of the efficacy of remdesivir treatment in the context of a MER

242 ters and to elucidate the mode of action and efficacy of REP 2139-Ca against HDV in 12 treatment-naiv

243 d CNTs for dsRNA delivery could increase the efficacy of RNA interference in insect pest species.

244 l adjunctive approach to improve therapeutic efficacy of SSRI antidepressants.

245 d trials (RCTs) investigating the safety and efficacy of systemic treatments for AD up to February 20

246 t HOCl stress and therefore may increase the efficacy of the innate immune response.

247 toichiometry all play important roles in the efficacy of the ionophoric activity.

248 We sought to evaluate safety and efficacy of the JAK1/2 inhibitor ruxolitinib in patients

249 This study evaluated the efficacy of the Placebo-Control Reminder Script (PCRS),

250 way collapsibility of DS and to evaluate the efficacy of therapeutic interventions for breathing and

251 However, the efficacy of these agents often decreases over time, whic

252 We aimed to test the efficacy of these drugs in an efficient manner with resp

253 Naturally, the efficacy of these therapeutic strategies will depend on

254 The encoding efficacy of this large synapse depends on its activity r

255 ur multicenter trial demonstrated safety and efficacy of transplantation of 30 HCV-viremic kidneys in

256 l murine cancer models to test the antitumor efficacy of undifferentiated monocytes loaded with prote

257 ized mouse models cannot be used to test the efficacy of vaccines expressing alpha-Gal epitopes becau

258 The tolerability and efficacy of venetoclax in combination with intensive che

259 teins in H. zea will challenge the long-term efficacy of Vip3Aa technology.

260 elevated IgG4 levels may be a biomarker for efficacy of VIT in cMCD patients, as it correlates with

261 n malaria infection (CHMI) to assess vaccine efficacy offer a unique opportunity to study the immune

262 The primary efficacy outcome was stroke and the primary safety outco

263 The primary efficacy outcome, symptomatic recurrent venous thromboem

264 his study was to systematically evaluate the efficacy, outcomes, and complications of gamma knife rad

265 g fewer IOP elevations with EGP-437, similar efficacy overall, and possibly better efficacy in more s

266 pendent A(3)AR-selective nucleosides are low efficacy partial agonists and novel, nuanced modulators

267 Safety, efficacy, predictability, astigmatic vector changes, con

268 Endpoints consisted of (i) technical efficacy; primary - requiring one treatment, and seconda

269 depressants are widely prescribed, but their efficacy relative to placebo is modest, in part because

270 XL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies.

271 The efficacy results trended modestly in favor of the treatm

272 ntimicrobials for treatment under the Animal Efficacy Rule, where efficacy can be demonstrated in 1 o

273 This review summarizes the clinical efficacy, safety and tolerability of pitolisant in treat

274 ejection fraction with T2DM to assess their efficacy, safety, and risk-benefit profile.

275 Our aim was to determine the efficacy, safety, and tolerability of berotralstat in pa

276 nt drug mechanisms that could yield superior efficacy, safety, and tolerability.

277 se-3 randomized clinical trials (AMAGINE -1 [Efficacy, Safety, and Withdrawal and Retreatment With Br

278 d pursuit of appropriately reduced intrinsic efficacy should guide development of safer opioids.

279 a, and CXCL9 which had a combined diagnostic efficacy similar to immunoglobulin G (IgG) index and neu

280 In vitro bactericidal efficacy studies were carried out using 5 different FARs

281 Dose-ranging efficacy studies were performed on a 1 T MRI scanner usi

282 l in terms of their contribution to catalyst efficacy, suggesting that tuning individual electronic e

283 programs, including natural enemy selection, efficacy testing and quantification of non-target impact

284 Alongside efficacy testing of novel therapies, effects on pulmonar

285 nd (3) C15:0 has demonstrated activities and efficacy that parallel associated health benefits in hum

286 mAbs) have demonstrated significant clinical efficacy, there is also the potential for severe adverse

287 correlation = 0.93 when comparing predicted efficacies to measured efficacies for >5000 combinations

288 ry vaccines and allows the bar on safety and efficacy to be lowered, risking people's health and unde

289 g PEG~TLZ for humans that may be superior in efficacy to daily oral TLZ and would be useful for treat

290 finally evaluated for their tumor inhibition efficacy using in vivo MMTV-neu transplantation mouse mo

291 an be used as a treatment for dysphagia, its efficacy varies across individuals.

292 te that proximal threats impaired extinction efficacy via persistent multivariate representations of

293 While Zostavax efficacy wanes with age, Shingrix protection retains its

294 Efficacy was defined as complete response (CR) rate on e

295 Efficacy was tested using the very aggressive human trip

296 dose, the primary endpoint (overall vaccine efficacy) was assessed in the first 11 months, and the s

297 ffective glioblastoma treatment by improving efficacy while reducing systemic toxicities.

298 : (225)Ac-L1 demonstrated activity-dependent efficacy with minimal treatment-related organ radiotoxic

299 ion of anise seed extract and to compare its efficacy with the bulk extract against pathogenic bacter

300 w-up duration, and determination of clinical efficacy would require larger randomized trials with mor