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Y ear: 2001 PO PU L A T IO N G roupssimilar atbaseline:Y es C H A R A C T ER IST IC S: A lzh eimer classification:M oderate-Severe donepezil placebo M eanage(years): 73 cheap carafate 1000mg visa. Y ear: 2001 R ESU L T S: IntermediateO utcomeM easures(C ont’d buy 1000 mg carafate with mastercard. Y ear:2000 PO PU L A T IO N G roupssimilar atbaseline:Y es C H A R A C T ER IST IC S: A lzh eimer classification:M ild-m oderate donepezil placebo M eanage(years): 70. Y ear:2000 A DV ER SEEV EN T S: donepezil placebo O veralladverseeffectsreported: 40% (atleast3incidences/event) 25% (atleast3incidences/event) • Coldsyndrom e 7% 2% Significantdifferencesinadverse Coldsyndrom ewasreportedm orefrequentlyinD O N -treatedpatients(P <0. Y ear:2004 C ountry:M ultinational(U K ,F inland,G erm any,N orway) F U N DIN G : E isaiInc. Y ear:2004 PO PU L A T IO N G roupssimilar atbaseline:N o(genderdistributiondifferedsignificantly) C H A R A C T ER IST IC S: A lzh eimer classification:M ild-m oderate donepezil galantamine M eanage(years): 73. Y ear:2004 A DV ER SEEV EN T S: donepezil galantamine O veralladverseeffectsreported: 67. Y ear:2005 C ountry:A uthorsareG erm an--studiesfrom anycountrywereincluded F U N DIN G : N one DESIG N : Studydesign:SR N umber ofpatients:N R A IM S O F R EV IEW : Thisreview assessedthescientific evidencefortherecom m endationof thecholinesterase inhibitorsdonepezil,rivastigm ine,andgalantam inefortreatm entof A D. Y ear:2005 C H A R A C T ER IST IC S O F D urationof treatm entvariedbetweensix weeksandthreeyears;N um berof patientsincludedper IN T ER V EN T IO N S: studyvariedbetween27and978;A llstudiesincludedpatientswithanestablisheddiagnosisof probableorpossibleA lzheim er’sdisease,according totheN ationalInstituteof N eurologicaland Com m unicativeD isordersandStroke— A lzheim erD iseaseandR elatedD isordersA ssociationwith oneex ceptionwhereaD SM -IV diagnosisof dem entiawasusedforinclusion;F ourteenof 22trials usedtheA D A S-cog astheprim arym easurem entof efficacy;In12trials,theCIBIC-pluswasused toassessefficacy M A IN R ESU L T S: • M ethodologicalassessm entof allstudiesfoundconsiderableflaws:Theuseof several “prim aryendpointswithoutcorrectionform ultiplecom parisons. A ftercorrection,twoof thefivetrialsonrivastigm inedonotshow anysignificantbenefitonprim aryendpoint m easuresanym ore;m issing ITT analysis,asin15of the22trialspatientswereex cluded from analysisafterrandom ization;Inatleasteightof thetrialsthelastobservationcarried forward(L O CF )m ethodwasusedtoincludedropoutsintoendpointanalyses. A DV ER SEEV EN T S: D onepezil,rivastigm ine,andgalantam inecausedabroadspectrum of adverseevents— nausea, vom iting,diarrhea,andweightlosswerethem ostcom m on. Y ear: 2001 PO PU L A T IO N G roupssimilar atbaseline:Y es C H A R A C T ER IST IC S: A lzh eimer classification:M ild-m oderate donepezil placebo M eanage(years): 75. Y ear: 2001 R ESU L T S: IntermediateO utcomeM easures: • D ifferencesinm eanchangefrom baselinetoendpointforD O N differedfrom placeboforboth instrum entalA D L (P = 0. ST U DIES IN C L U DEDIN A totalof 7placebo-controlledR CT studieswereincluded,6of whichwerePhaseII orIII industry- M ET A -A N A L Y SIS sponsoredm ulti-centertrials:W ilkinsonetal. Y ear:1998 C ountry:N R F U N DIN G : Som eauthorsweresupportedbyParke-D avisandSm ithK lineBeecham DESIG N : Studydesign:M eta-analysisof individualpatientdata N umber ofpatients:1,984 A IM S O F R EV IEW : Todeterm inetheeffectsof TA C onthesym ptom sof A D interm sof cognitiveperform ance,clinicalglobal im pression,behavior,andfunctionalautonom y ST U DIES IN C L U DEDIN A totalof 12publishedandunpublishedstudiesidentifiedfrom theCochraneregistry;6crossoverstudies M ET A -A N A L Y SIS and6parallelgroup designs T IM EPER IO DC O V ER ED: Trialscom pletedbeforeJanuary1,1996 C H A R A C T ER IST IC S O F R andom ized,double-blind,placebo-controlledtrialsinwhichTA C hadbeengivenform orethan1day; IN C L U DEDST U DIES: treatm entcom parisonsof TA C vs. Y ear:1998 C H A R A C T ER IST IC S O F Thetrialsinvolveddosagesvarying from 20to160m g/d,varying durationof treatm ent(3-36wks),and IN T ER V EN T IO N S: varying tim esandfrequenciesof assessm ent;twostudiescontainedm orethan1TA C group withfix ed dosageregim ens;in3of therem aining 10studies,patientsweregiventheir“bestdose”basedonpre- random izationdosetitration,andintheother7studies,patientsweretitratedtotheirbestdoesbythe clinicianafterrandom ization,giving possiblem ax im um dosagesbetween80and120m g/d M A IN R ESU L T S: • InpooledITT analysisforM M SE scoresat12weeks,therewasa0. Y ear:2000 PO PU L A T IO N G roupssimilar atbaseline:Y es C H A R A C T ER IST IC S: A lzh eimer classification:M ild-m oderate galantamine24 mg/d galantamine32 mg/d placebo M eanage(years): 75. Y ear:2000 A DV ER SEEV EN T S: galantamine24 mg/d galantamine32 mg/d placebo O veralladverseeffectsreported: 92. Y ear: 1996 C ountry:U S F U N DIN G : E isaiA m erica,Inc. Y ear:1996 PO PU L A T IO N G roupssimilar atbaseline:Y es C H A R A C T ER IST IC S: A lzh eimer classification:M ildtom oderatelysevere donepezil1mg donepezil3mg donepezil5 mg placebo M eanage(years): 72. Y ear:1996 A DV ER SEEV EN T S: donepezil1mg donepezil3mg donepezil5 mg placebo O veralladverseeffectsreported: 64% 68% 67% 65% • N ausea/vom iting 7% 0% 10% 5% • D iarrhea 0% 3% 10% 3% • D izziness 5% 3% 8% 10% • N asalcongestion 2% 13% 5% 8% • Com m oncold 10% 5% 5% 5% 10% 5% 3% 8% • H eadache 10% 3% 3% 3% • F lushing 2% 10% 3% 5% • Coughing 2% 3% 10% 3% Significantdifferencesinadverse N R events: A N A L Y SIS: IT T :Y es Postrandomizationexclusions:N R A DEQ U A T ER A N DO M IZ A T IO N : M ethodnotreportedbutgroupswellbalanced A DEQ U A T EA L L O C A T IO N M ethodnotreported C O N C EA L M EN T : B L IN DIN G O F O U T C O M E Y es A SSESSO R S: A T T R IT IO N (overall): O veralllossto follow-up: 12. Y ear:1998 PO PU L A T IO N G roupssimilar atbaseline:Y es C H A R A C T ER IST IC S: A lzh eimer classification:M ildtom oderate donepezil5 mg donepezil10 mg placebo M eanage(years): 73. Y ear:1998 A DV ER SEEV EN T S: donepezil5 mg donepezil10 mg placebo O veralladverseeffectsreported: 68% 78% 69% • N ausea 7% 22% 8% • Insom nia 8% 18% 5% • D iarrhea 6% 13% 3% • U TI 6% 4% 13% Significantdifferencesinadverse N ausea,insom niaanddiarrheaweresignificantlym orecom m oninpatientstaking highdoseD O N than events: patientstaking placebo(P <0. Y ear:1998 PO PU L A T IO N G roupssimilar atbaseline:N o;m eanageof D O N 10m g/dgroup was2yearsolderthan C H A R A C T ER IST IC S: placebo(P = 0. Y ear:1998 A DV ER SEEV EN T S: donepezil5mg donepezil10mg placebo O veralladverseeffectsreported: N R N R N R • F atigue 5% 8% 2% • D iarrhea 9% 17% 7% • N ausea 4% 17% 4% • V om iting 3% 10% 2% • M usclecram ps 6% 7% 2% 10% 8% 1% • D izziness Significantdifferencesinadverse Y es;D O N 10m g/dhadsignificantlym orereportsof fatigue,diarrhea,nausea,vom iting andm uscle events: cram ps(P ≤ 0. Y ear:1999 PO PU L A T IO N G roupssimilar atbaseline:Y es C H A R A C T ER IST IC S: A lzh eimer classification:M ildtom oderatelysevere rivastigmine1-4 mg/d rivastigmine6-12 mg/d placebo M eanage(years): N R N R N R Sex(% female): N R N R N R Eth nicity: N R N R N R O th er germanepopulationqualities: • BaselineA D A S-Cog 23. Y ear:1999 A DV ER SEEV EN T S: rivastigmine1-4 mg/d rivastigmine6-12 mg/d placebo O veralladverseeffectsreported: 71% 91% 72% • N ausea 17% 50% 10% • V om iting 8% 34% 6% • D izziness 10% 20% 7% • H eadache 7% 19% 8% • D iarrhea 10% 17% 9% 3% 14% 2% • A norex ia 5% 12% 3% • A bdom inalPain 2% 10% 3% • F atigue 1% 10% 2% • M alaise Significantdifferencesinadverse A lladverseeventsoccurredsignificantlym oreoftenforhighdoseR IV thanplacebo(P <0. Y ear:1998;2002;2004 C ountry:M ultinational F U N DIN G : N ovartisPharm aceutical DESIG N : Studydesign:M eta-analysis N umber ofpatients:2,126 A IM S O F R EV IEW : Toassesstheefficacyof R IV inpatientswithm ildtom oderatelysevereprobableA D. ST U DIES IN C L U DEDIN ThreeR CTs(2publishedR osler1998,Corey-Bloom 1998;1unpublished) M ET A -A N A L Y SIS T IM EPER IO DC O V ER ED: N R C H A R A C T ER IST IC S O F R andom ized,controlled,double-blindedtrialswith26weeksstudydurations. Y ears:1998;2002;2004 C H A R A C T ER IST IC S O F R IV 1-4m g/dor6-12m g/d(publishedtrials)or3m g/d,6m g/d,12m g/d(unpublished)for26weeks IN T ER V EN T IO N S: M A IN R ESU L T S: R IV -treatedpatientsex periencedstatisticallysignificantbetterresultsthanplacebo-treatedpatientsin: Cognition:A D A S-Cog,placebo-2. Subgroup analysisof thepooledpopulationpresentedthatnicotineuseattenuatesthedose-responsecurveof R IV andolderpatientsex periencedgreaterbenefitfrom R IV R etrospectivesubgroup analysisof patientswithm oderatelysevereA D (n= 117;M M SE 10– 12)revealed asignificantlysm allerdeclineof A D A S-cog (ITT-L O CF :0vs.

Long-term darifenacin treatment for overactive bladder in patients aged 65 years and older: analysis of results from a 2-year buy 1000mg carafate amex, open-label extension study buy 1000 mg carafate amex. Treatment of overactive bladder in the older patient: pooled analysis of three phase III studies of darifenacin, an M3 selective receptor antagonist. Wagg A, Wyndaele JJ, Sieber P, Wagg A, Wyndaele J-J, Sieber P. Efficacy and tolerability of solifenacin in elderly subjects with overactive bladder syndrome: a pooled analysis. Efficacy and tolerability of tolterodine extended release in male and female patients with overactive bladder. Solifenacin treatment for overactive bladder in Hispanic patients: patient-reported symptom bother and quality of life outcomes from the VESIcare Open-Label Trial. Tolterodine does not affect the human in vivo metabolism of the probe drugs caffeine, debrisoquine and omeprazole. Brynne N, Dalen P, Alvan G, Bertilsson L, Gabrielsson J. Influence of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamic of tolterodine. Brynne N, Forslund C, Hallen B, Gustafsson LL, Bertilsson L. Ketoconazole inhibits the metabolism of tolterodine in subjects with deficient CYP2D6 activity. Pharmacokinetics and pharmacodynamics of tolterodine in man: a new drug for the treatment of urinary bladder overactivity. International Journal of Clinical Pharmacology & Therapeutics. Overactive bladder Page 52 of 73 Final Report Update 4 Drug Effectiveness Review Project 138. Brynne N, Svanstrom C, Aberg-Wistedt A, Hallen B, Bertilsson L. Fluoxetine inhibits the metabolism of tolterodine-pharmacokinetic implications and proposed clinical relevance. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. Tolterodine treatment improves storage symptoms suggestive of overactive bladder in men treated with alpha-blockers. Safety and tolerability of tolterodine for the treatment of overactive bladder in men with bladder outlet obstruction. Tolterodine extended release with or without tamsulosin in men with lower urinary tract symptoms including overactive bladder symptoms: effects of prostate size. Effect of tolterodine extended release with or without tamsulosin on measures of urgency and patient reported outcomes in men with lower urinary tract symptoms. Kaplan SA, Roehrborn CG, Chancellor M, Carlsson M, Bavendam T, Guan Z. Extended- release tolterodine with or without tamsulosin in men with lower urinary tract symptoms and overactive bladder: effects on urinary symptoms assessed by the International Prostate Symptom Score. Overactive bladder Page 53 of 73 Final Report Update 4 Drug Effectiveness Review Project Appendix A. Glossary This glossary defines terms as they are used in reports produced by the Drug Effectiveness Review Project. Some definitions may vary slightly from other published definitions. Absolute risk: The probability or chance that a person will have a medical event. It is the ratio of the number of people who have a medical event divided by all of the people who could have the event because of their medical condition.

However buy carafate 1000mg low price, even after SMART order carafate 1000 mg on-line, not all questions were answered. A striking fact was the high incidence of clinical occurrences compared to Staccato, a study involving 430 patients. As measured by the AIDS/mortality rates of ART, there should have been at least 17 cases in Staccato – instead there was not one. Moreover the significantly higher risk of an AIDS-defining malignancy during therapy interruption (Silverberg 2007) was questionable as the majority of the patients who developed KS or lym- phoma in SMART had already suffered from AIDS illnesses before. Why were these patients enrolled in the SMART study? One can only speculate about the increased cardiovascular, renal and hepatic inci- dents in the interruption group. How many patients interrupted therapy that should not have? How many patients with chronic hepatitis B experienced a HBV rebound during interruption, how many patients with previous HIVAN developed renal prob- lems, how many patients decided to stop concomitant medications (statins) that led to a cardiovascular event? However, there are some newer studies that show an increase of inflammatory or coagulation parameters during therapy interruption (Kuller 2008, Calmy 2009, Baker 2011, Olmo 2012). Cystatin C, a parameter for renal dysfunction, also increases (Mocroft 2009). Especially the argument that therapy interruptions improve quality of life is no longer the case. One can discuss higher values for initiation and interruptions, but there will certainly not be any second SMART with new starting/stopping values for some time. Patients should always be encouraged to continue ART. Thanks to the new classes, the options have widened, enabling us to respond to side effects. If the patient, after discussion, still wishes to interrupt therapy the wish should be respected. The inter- ruption will happen anyway with or without the doctor’s agreement. A monitored interruption is better than one done secretly behind the physician’s back. Under strict surveillance the risk for complications is rather low, but again, the patient should consider the possibilities of changing treatment vs leaving it. Practical tips for treatment interruptions • If there are no problems with ART, there is no reason to stop it. A supervised treatment inter- ruption is better than one undertaken without the awareness of the clinician. References Ananworanich J, Kerr SJ, Vernazza P, et al. Genital shedding of HIV after scheduled treatment interruption. Recurring thrombocytopenia associated with structured treat- ment interruption in patients with HIV infection. TILT: a randomized controlled trial of interruption of antiretroviral therapy with or without interleukin-2 in HIV-1 infected individuals. A randomized pilot study comparing combination therapy plus enfuvirtide versus a treatment interruption followed by combination therapy plus enfuvirtide. A randomized trial of treatment interruption before optimized antiretrovi- ral therapy for persons with drug-resistant HIV: 48-week virologic results of ACTG A5086. Bernasconi E, Vernazza PL, Bernasconi A, Hirschel B. HIV transmission after suspension of highly active anti- retroviral therapy. The role of hydroxyurea in enhancing the virologic control achieved through structured treatment interruption in primary HIV infection: final results from a randomized clinical trial (Pulse). When to stop ART 243 Bonhoeffer S, Rembiszewski M, Ortiz GM, Nixon DF. Risks and benefits of structured antiretroviral drug therapy interruptions in HIV-1 infection. Incidence and risk factors of thrombocytopenia in patients receiv- ing intermittent antiretroviral therapy: a substudy of the ANRS 106-window trial.

Authors report 9 laboratory ADEs in parva: 22% simva vs proven carafate 1000mg. One simva patient experienced significant elevation in CK after beginning R buy carafate 1000 mg otc, DB, MC, not ITT LDL-c reduction from baseline at 6 weeks: rigorous exercise program the day before. Simva was stopped and restarted parva: 17% with no further incident. One parva patient developed a rash and was 48 patients randomized simva: 29% (no p-value provided) withdrawn. Statins Page 112 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Funding Source Lefebvre et al. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Inclusion Criteria/ Patient Clinical Trial Population Exclusion criteria Intervention Malini et al. Statins Page 114 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Results (mean changes in lipoprotein levels) Harms/Comments Malini et al. No patient R, OL, ITT LDL-c reduction from baseline at 6 weeks: withdrew from the study due to ADEs. R, OL, C, not ITT LDL-c reduction from baseline at 8 weeks: parva: 23. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Funding Source Malini et al. R, OL, C, not ITT 74 patients randomized 16 weeks Statins Page 116 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Inclusion Criteria/ Patient Clinical Trial Population Exclusion criteria Intervention Stalenhoef et al. Steinhagen-Thiessen Men or women 21-71 years with Patients with diabetes [fasting glucose >6. Statins Page 117 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Results (mean changes in lipoprotein levels) Harms/Comments Stalenhoef et al. No clinically R, DB, MC, not ITT LDL-c reduction from baseline at 18 weeks: significant increases in ALT/AST or CK. Most common treatment-related ADE was musculoskeletal complaints in 1994 LDL-c reduction from baseline at 6 weeks: simva group vs. No details on 3rd 281 patients randomized LDL-c reduction from baseline at 12 weeks: withdrawal. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Funding Source Stalenhoef et al. R, DB, MC, not ITT 281 patients randomized 12 weeks Statins Page 119 of 395 Final Report Update 5 Drug Effectiveness Review Project Evidence Table 1. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Inclusion Criteria/ Patient Clinical Trial Population Exclusion criteria Intervention Sweany et al. Simva 207 mg/dl before baseline and treatment with immunosuppressive drugs. Doses doubled if LDL-c at weeks 6 and 12 were >130 mg/dl, up to a maximum of 40 mg qd for each statin. Misc Gratsianskii N, et al Men and postmenopausal women Recent ACS, receiving statins, and patients with evident systemic Series 1- control vs. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Results (mean changes in lipoprotein levels) Harms/Comments Sweany et al. Reasons in parva group: R, DB, MC, not ITT LDL-c reduction from baseline at 6 weeks: headache and tinnitus, rash, abdominal pain, GI complaints and dizziness. CK elevation in other HDL-c increase from baseline at 18 weeks: myalgia reports not clinically significant. Trigs reduction from baseline at 18 weeks: parva 14% Nonequivalent doses compared. Prava40 unknown, SC, not ITT (n=25) -23% (atorva10 and prava40 vs. Trials comparing LDL-c lowering/HDL-c raising abilities of 2 or more statins Clinical Trial Funding Source Sweany et al.

Electronic database searches were supplemented by hand searches of reference lists of included studies and reviews effective carafate 1000mg. In addition cheap carafate 1000mg without a prescription, we searched the US Food and Drug Administration (FDA) Center for Drug Evaluation and Research, the Canadian Agency for Drugs and Technologies in Health, and the National Institute for Health and Clinical Excellence web sites for medical or statistical reviews and technology assessments. Finally, we searched dossiers of published and unpublished studies submitted by pharmaceutical companies. Study Eligibility All citations were reviewed for inclusion using the criteria shown in Table 2. Two reviewers independently assessed titles and abstracts of citations identified from literature searches. Full- text articles of potentially relevant citations were retrieved and assessed for inclusion by two reviewers, and disagreements were resolved by consensus. Results published only in abstract form (such as a conference proceeding) were not included, because they typically provided insufficient detail for adequate quality assessment. Study inclusion and exclusion criteria Included populations • Adults and children • Type 1 and type 2 diabetes mellitus Excluded populations • Gestational diabetes and Type 1 and type 2 diabetes mellitus in pregnancy Subgroups of interest • Demographic characteristics (age, race, and sex) • Concomitant medications and drug-drug interactions • Comorbidities such as obesity and cardiovascular disease • History of hypoglycemic episodes • Baseline A1c • Drug specific-subgroups: pramlintide, renal insufficiency; exenatide, renal insufficiency; and sitagliptin, renal and hepatic insufficiency Included health outcomes • All-cause mortality • Microvascular disease: chronic kidney disease including renal dialysis, renal transplantation, and end-stage renal disease; retinopathy including proliferative retinopathy and blindness; and peripheral neuropathy • Macrovascular disease: cardiovascular events, cardiovascular mortality, stroke or transient ischemic attack, coronary heart disease, cardiovascular procedures, and extremity amputation • Other complications of diabetes: lower extremity ulcers • Quality of life including treatment satisfaction Diabetes Page 10 of 99 Final Report Drug Effectiveness Review Project • Other: hospitalization and medical visits related to diabetes care Included intermediate outcomes • Glycemic control: fasting glucose, post-prandial glucose, and A1c • Change in weight • Time to treatment failure Included safety and harms outcomes • Overall adverse events • Withdrawals due to adverse events • Major adverse events including but not limited to diabetic ketoacidosis and non-ketotic hyperosmolar coma • Specific adverse events including but not limited to hypoglycemia, liver toxicity, liver function abnormalities, gastrointestinal effects, adverse changes in lipid concentrations, and weight gain • Adverse events specific to drug class: DPP-4 inhibitors, infection and neoplasm including cancer; amylinomimetics, neoplasm including cancer Included study designs • All studies (efficacy, effectiveness, and harms) were required to have ≥12 weeks of follow-up, the minimum study duration needed to adequately assess change in glycemic control. We recorded intention-to-treat results when reported. For included systematic reviews, we abstracted the searched databases, study eligibility criteria, numbers of studies and patients represented, characteristics of included studies, data synthesis methods, and main efficacy and safety results. Validity Assessment We assessed the internal validity (quality) of trials based on the predefined criteria listed in Appendix C. These criteria are based on the US Preventive Services Task Force and the National 4, 5 Health Service Centre for Reviews and Dissemination (UK) criteria. We rated the internal validity of each trial based on the methods used for randomization, allocation concealment, and blinding; the similarity of compared groups at baseline; maintenance of comparable groups; adequate reporting of dropouts, attrition, crossover, adherence, and contamination; loss to follow-up; and the use of intention-to-treat analysis. We considered methods to meet criteria for intention-to-treat analysis if outcomes for at least 95% of participants were analyzed according to the group to which they were originally assigned. We considered total attrition of ≥15% in any of the treatment arms to be excessive. Diabetes Page 11 of 99 Final Report Drug Effectiveness Review Project Trials that had fatal flaws were rated poor quality. Trials that met all criteria were rated good quality and the remainder rated fair quality. As the fair-quality category is broad, studies with this rating vary in their strengths and weaknesses: The results of some fair-quality studies are likely to be valid, while others are only probably valid. A poor-quality trial is not valid; the results are at least as likely to reflect flaws in the study design as the true difference between the compared drugs. A fatal flaw is reflected by failing to meet combinations of items of the quality assessment checklist that work together to suggest a potential for bias. We assessed the quality of systematic reviews using pre-defined criteria developed by Oxman and Guyatt (See Appendix C). These included adequacy of literature search and study selection methods, methods of assessing validity of included trials, methods used to combine studies, and validity of conclusions. Data Synthesis A qualitative analysis of the available evidence or lack of evidence was undertaken. We constructed evidence tables (included as a separate document) showing the study characteristics, quality rating, and results for all included studies. Pooled estimates of effect sizes were estimated by meta-analysis using random-effects 6 models. Results from each study were stratified by dose level of the drug intervention arms (high and low doses). Weighted mean differences between drug and control were calculated for outcomes (percent change in A1c, weight loss, fasting plasma glucose, and post-prandial glucose). Risk ratios between drug and control were pooled for withdrawals and adverse events.