Format Laporan Journal Reading

Judul Tulisan

: The Roche European American Cataract Trial (REACT): A randomized clinical trial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow progression of agerelated cataract.

Penulis

: The REACT Group (Leo T. Chylack, Jr. ;M.D.,Nicholas P. Brown, F.R.C.Ophth. ; Anthony Bron, F.R.C.Ophth. ; Mark Hurst, O.D. ; Wolfgang Kpcke, Ph.D. ; UtaThien, Ph.D. ; Wolfgang Schalch, Ph.D.)

Nama jurnal, volume, nomor dan tahun terbit Vol.9, No. I, 2002 Analisis PICO Patient Intervention Comparison Outcome

: Ophthalmic Epidemiology,

: European and American with early cataract. : oral antioxidant micronutrient mixture : placebo : Grup dengan oral antioxidant micronutrient menunjukkan

perlambatan pada progresi opacity lensa yang signifikan dibanding dengan placebo.

Topik Judul dan abstrak

No

Keterangan

Ditemukan di halaman berapa, jelaskan

1 1. Indicate the studys material (ex 1. subjek penelitian terlihat pada plant) animal) 2. Provide in the abstract an Four-hundred-and-forty-ve informative and balanced summary patients were eligible; 297 of what was done and what was were randomized; 231 (78%) were and subject (human or abstrak bagian patient.

found 1. Menjelaskan subyek penelitian 2. Memberikan ringkasan

followed for two years; 158 (53%) were followed for three years; 36

yang (12%) were followed for four years.

informatif dan seimbang atas apa Twelve patients died during the trial yang dilakukan dan apa yang (9 on vitamins; 3 on placebo (p = ditemukan (hasil) dalam abstrak 0.07)). There were no serious safety issues.

2. untuk perlakuan partisipan terlihat dalam bagian intervention After a three-month placebo runin, patients were randomized by clinical center to the vitamin or placebo groups and followed every four months.

Sementara hasilnya terlihat di bagian result dan conclusion RESULT.

There

were

no

statistically signicant differences between the treatment groups at baseline. The characteristics of dropouts and the mean follow-up group times were by the

treatment

same.After two years of treatment, there was a small positive treatment effect in U.S. patients (p = 0.0001); after three years a positive effect was apparent

(p = 0.048) in both the U.S. and the U.K. groups. The positive effect in the U.S. group was even greater after three years: (IPO = 0.389 (vitamin) vs. IPO = 2.517 (placebo); p = 0.0001). There was no statistically signicant benet of treatment in the U.K. group. In spite of nearly perfect randomization into

treatment groups, the U.S. and U.K. cohorts differed signicantly CONCLUSION.Daily use

of

the

afore-mentioned micronutrients for three years produced in a small of

deceleration ARC. Introduksi Latarbelakang 2

progression

Explain the scientific background Halaman kedua dan ketiga (50-51). and rationale for the investigation Several studies in the past 10 being reported years have suggested that Menjelaskan latar belakang yang antioxidant vitamins (C and E) and ilmiah dan rasional mengapa carotenoids reduce the risk of agerelated cataract (ARC). Many of these publications stressed the need for prospective, randomized, double-masked clinical trials of the efficacy of anti-oxidant vitamins and micronutrients in slowing

penelitian perlu dilakukan

progression of ARC.

ARC is the leading cause of blindness worldwide. In addition

to

reducing

the

financial expenditures for cataract surgery, uch treatment could offer individuals with early cataract the possibility of avoiding cataract surgery altogether.

Tujuan

State including

specific any

objectives, Halamankedua (50). prespecified to determine if oral supplementation with a mixture of

hypotheses Menentukan tujuan

spesifik, anti-oxidant

micronutrients

termasuk hipotesis yang diajukan.

[mg/day] b-carotene [18], vitamin C [750], and vitamin. E [600] could slow the progression of early agerelated cortical [C], nuclear [NO], or posterior subcapsular [P] cataract

Bahan dan Cara Bahan 4 Clearly defined how the material Halaman ketiga (51) pada paragraf were collected and prepared Menjelaskan bagaimana pertama data patients Patients material and methode

dikumpulkan dan disiapkan. were recruited

consecutively from outpatient ophthalmology clinics in the United States (U.S.) and the United

Kingdom (U.K.). The U.S. center was the Brigham and Womens Hospital in Boston; the U.K. centers were the

Nufeld Laboratory of Ophthalmology in Oxford and the

University of Bradford. The tenets of the Declaration of Helsinki 23 were followed. Each centers

Human Studies Committee approved the protocol. Written informed consent was obtained from all patients.Of 445 eligible patients, 315 entered into the placebo run-in phase of the trial. The recruitment and randomization took approximately 1.5 years

(Figures 1 & 2) Participant penelitian Subyek 5 Eligibility criteria for participant / Halaman ketiga hingga kelima (51subject Kriteria subyek penelitian 53). Pada sub-bagian inclusion

criteria dijabarkan kriteria per poin secara rinci, dan didukung dengan hasi linklusi/eksklus ipadaFig. 1. Flow chart.

Inclusion/exclusion determine eligibility were

criteria

to

applied

during

recruitment. If they were violated, the subject was deemed ineligible for the run-in phase. Each patient [a] provided written informed consent, [b] was able to attend for all visits,

and [c] was at least 40 years old. [d] At least one eye met the following ocular criteria: 1. 2. cataract immature extraction idiopathic unlikely senile

within two years,

cataract present in one or both eyes, 3. (U.S. patients) presence of

minimal cataract by Lens Opacities Classication System [LOCS II] 14 criteria: NC, NO, and P grades: >0, and 1; C grade: >0, and trace, 4. (U.K. patients) presence of

cataract of minimal Oxford grade: cortical and posterior subcapsular grades: grade I; nuclear brunescence: grade II; and white nuclear scatter: grade II. 5. If both eyes met the inclusion criteria, and cataracts were of different types, the cataract type in the eye with the worse visual acuity determined the group for randomization. If an eye had more than one type of cataract, the morphological type that in the clinicians opinion to was the more acuity

destructive determined

visual

the group for randomization 6. logMAR acuity 0.5, Intervensi 6 Precise details of the intervention Halaman kelima (53). Study design, intended for each group and how bagian overview, dipaparkan waktu and when they were actually dan proses berjalannya penelitian. administered Menjelaskan intervensi yang The REACT study began on

dilakukan pada tiap kelompok October 20, 1990 and was perlakuan dengan detail. concluded on July 20, 1995. It Termasuk bagaimana dan kapan began with Visit 1 at the beginning intervensi diberikan. of a three-month placebo run-in

period, after which the patient was seen for Visit 2 and randomization was carried out

Halamankeenam (54) bagian length of trial, berisi rencana alokasi waktu dan beberapakendala. The original protocol specied the length of the trial as two years with patients

continuing on treatment until the last randomized patient completed two years of follow-up. At the ninth meeting of trial investigators a formal amendment to the protocol was adopted: . . . that the trial be continued until each subject has com-

pleted at least 11 visits, which is equivalent to a treatment duration of three years. This ofcial

recommendation was based in part on an interim analysis that, in spite of revealing signicant difference between groups A and B, showed continued follow-up. At this meeting the outcome data were not presented in a manner in which the identity of the treatment (vitamin or placebo) could be inferred. In accord with this amendment, the three-year data, rather than the two-year data, were used for the primary analyses.Due to the long period of recruitment (approximately 1.5 years), some patients completed three or more years before the last randomized patient completed was two years. a trend that justied no statistically

Recruitment primarily

prolonged

because of the difculty in nding patients who satised the complex inclusion/exclusion criteria.

Bagian randomization, berisi tentang

pengelompokan,

pelaksana

intervensi, intervensi itu sendiri, dan nama metode yang digunakan. The unit of randomization was the individual. For randomization stratied by patients clinical were center

(Boston,Bradford, Oxford). Each group was further stratied for randomization according to cataract class: C, NO, and P. There was no stratication according to age. If both eyes of a patient had mixed cataracts (more than one class of cataract in a given lens), then the predominant cataract type in the eye with the worse visual acuity determined the group for randomization. The

treatment allocation (vitamins or placebo) was given at random in each of the 9 groups (3 centers 3 classes of cataract).

Randomization was calculated by Efrons biased coin method.

Pada kedua bagian method, berisi pelaksanaannya, siapa saja yang berhubungan dengan penelitian ini dan perannya. Method of allocation concealment and timing of the assignment The

intervention assignment and the timing of the assignments were not known to the participants, center administrators, or clinicians until the study and data sets were closed. Method used to separate the

generator from the executor of the assignment The generator of the assignment (the individual who generated, using a bias-free method, the listing that identied the intervention assignment for every

participant) was located in Munich, Germany. The executor of the assignment (the individual who, having determined eligibility, a participants the

consulted

assignment system for that participants intervention designation) was also located in Munich, Germany. The persons who prepared the randomization scheme were not involved in

determining administering intervention, outcomes. or

eligibility,

assessing

Bagian masking, halaman ketujuh (55), menjelaskan apa yang menjadi

intervensi yang akan diberikan pada partisipan, Capsules dan sekilas tentang

bagaimana pemberiannya. for this trial were

provided by HLR and contained 200mg all-rac

alpha-tocopherol acetate (Vitamin E), 250mg ascorbic acid, and 6mg bcarotene (in the form of beadlets). The placebos were identical in appearance and contained corn oil as the major constituent. At each visit, active or placebo capsules were dispensed packs, capsule requirement for the four-month period between two consecutive visits. Three capsules per day were taken with meals. See Figure 3 for evidence that there was good in one-week to blister the

enough

cover

compliance with the intervention schedule and no apparent vitamin

supplementation by patients on placebo Untuk evaluation, halaman ketujuh (55) berisikan rincian tentang apa saja yang diukur dan meode atau

cara pengukurannya, hingga halaman kesembilan (57), data hasil ada pada tabel-tabel yang ada pada halaman 62-65, 67, 69-70. Outcome 7 Clearly defined primary and Halaman kesembilan (57). Pada

secondary and,

outcome

measures Criteria for Response, bagian main any endpoints, dijelas kanapa yang

when

applicable,

methods used to enhance the utamanya diukur pada penelitian ini, quality of measurements (e.g., yaitu progresi kataraknya, dengan multiple observations, training of penjelasan. Dalam plasma analyses, assessors). Menjelaskan merupakan hal lain yang juga diukur pengukuran dalam penelitian semua ini, adalah

outcome, baik utama maupun pengukuran sekunder, plasma

kandungan data

selama

penelitian,

lengkap terdapat padaTable 2 di halaman keempat belas hingga

kelima belas (62-63) danTable 3 (6465). Besar sampel 8 Subject number used in the study Jumlah subyek penelitian. Terdapat di halaman 61 Table 3 contains baseline data relevant to this trial for the 158 patients who completed the study (the completers). Metode statistik 9 Statistical compare methods groups for used to Halaman kesepuluh hingga kedua

primary belas (58-60). Pada statistic, bagian overview, dijelaskan secara ringkas metode statistic yang

outcome(s) and other outcome

Metode statistik yang digunakan mengenai untuk membandingkan satu dengan

hasil digunakan, dalam hal ini,yaitu, ITT yang (intention-to-treat).Selain dijelaskan hal-hal itu, lain juga yang

kelompok kelompok

digunakan dalam memperoleh hasil statistic, yaitu, macam analisis, dan ketentuan-ketentuan, yang nantinya

akandijelaskan hasil(result). Hasil Alur penelitian 1 0

lebih

lanjut

di

Defining the periods of study and Halaman kedua belas hingga ketiga follow-up belas (60-61). Terdapat pada subbab

Menjelaskan waktu penelitian dan result, bagian patient population, follow-up sebelumnya pada Figure sudah I, digambarkan dan patients,

overview berisi pnjelasan ringkas tentang perekrutan partisipan dan proses follow-up. Paragraph

selanjutnya merincikan alasanya dan partisipan yang tidak ikut serta pada saat masih berjalannya penelitian dan perbandingannya dengan partisipan yang berpartisipasi hingga akhir.

Status pasien pada saat awal akan diberikan dan intervensi (visitasikedua) penelitian patient

setelah

selesai bagian

dijelaskan

pada

characteristic, dandidukung dengan data padaTable 2 dan Table 3. Bagaimana inervensi proses pemberian pada bagian

dijelaskan

treatment delivery, halaman 66. Outcomedanestima si 1 1 For each primary and secondary Halaman kedelapan belas hingga outcome, a summary of results for keduapuluh tiga (66 71). Pada bagian each group . outcome analyisis by treatment, pertama memaparkan

Untuk tiap outcome utama dan paragraph

sekunder, ringkasan atas hasil hasil yang diperoleh, yaitu, terdapat bagi tiap kelompok. pengurangan bertambahnya opasitas pada grup dengan intervens

ipemberian vitamin dibanding grup

dengan

placebo.Paragraph

selanjutnya adalah menerang kanapa yang telah terdata pada table 4 (main outcome), table 5 (measures of visual function), generalized dan table 6 (GEE-

estimation

equetion-

analyses). Diterangkan juga keadaan yang membahayakan yang

ditemukan selama penelitian pada bagian adverse events. Diskusi Interpretasi 1 2 Interpretation of the results, taking Halaman kedua puluh tiga hingga into account study hypotheses, kedua puluh sembilan (71-77). Pada sources of potential and with the bias or paragraph kedua, After two years of there was a small of positive treatment effect in U.S. patients (p = 0.0001).This positive hasil, effect was even greater after three hipotesis years: (IPO = 0.389 (vitamin) vs. IPO bias atau = 2.517 (placebo); p = 0.0001). After years of treatment the dangers treatment,

imprecision associated

multiplicity

analyses and outcomes. Interpretasi memperhitungkan penelitian, sumber

ketidaktepatan dan bahaya yang three

berhubungan dengan keragaman positive effect was apparent (p = analisis dan outcome. 0.048) in the entire cohort. These results suggest that the daily use of the afore-mentioned micronutrients for three years

produced a small deceleration in progression of ARC.

Pada paragraf akhir bagian bawah halaman kedua puluhdelapan (76), mengenai bias, We have considered

whether biases affected the REACT trial and have concluded that they did not.

Generalizability

1 3

Generalizability (external validity) Halamankeduapulusdelapan of the trial findings.

(75).

The profile suggested that U.K. well-nourished than U.S. subjects. That the beneficial effect appeared earlier in the U.S. group than in the U.K. group is most intriguing and may be due to the differing health and nutrition of the two groups. .the greater benefit of vitamin treatment cataract. The most striking differences was seen in the

Apakah hasil penelitian dapat subjects were less healthy and less digeneralisasikan di masyarakat.

population with the less severe

between U.K. patients and U.S. patients in this trial were the lower baseline levels of serum vitamins in the U.K.

Bahwa pada masyarakat, perbedaan regional atau tempa ttinggal dapat mempengaruhi besar nilai yang

diperoleh dalam penelitian. Dalam hal ini lebih terutama karena perbedaan nutrisi. Selain itu, derajat katarak juga

mempengaruhi, makin ringan maka nilai dari terapi vitamin lebihbesar. Jenis katarak cortical nilai efek (C) lebih

lebihmenunjukkan

besar daripada posterior subcapsular (P), dannuclear cataract (NO).

Overall evidence

1 4

General

interpretation

of

the Halamankeduapuluhsembilan

(77).

results in the context of current The deceleration may be greater evidence. Interpretasi umum terhadap hasil dalam konteks bukti terkini. The therapeutic effect was greater in U.S. than U.K. patients and may be due to the better nutritional status in the former group. .the efficacy of vitamin treatment as a function of the maturity of the cataract suggested that the in C than in P and NO cataract.

treatment was effective both in early and moderately advanced stages of cataract progression.