The US Food and Drug Administration (FDA) has put a class of antiemetic drugs, including ondansetron (Zofran, GlaxoSmithKline, and Zuplenz, Par Pharmaceutical), on its latest quarterly list of products to monitor because of potential signals of an increased risk for serotonin syndrome.
The beta blocker metoprolol succinate (Toprol-XL, AstraZeneca) also landed on the list, posted on the FDA Web site last month, because of reports that suggested therapeutic ineffectiveness.
The agency received reports of possible adverse events for these products in the FDA Adverse Event Reporting System (FAERS) database during the first 3 months of 2013. The FDA cautions that an appearance on the watch list does not mean that the agency has concluded that the drug poses the health risk reported through FAERS. What it does mean is that the FDA will investigate whether there is a causal connection. If there is one, the agency would consider a regulatory action such as collecting more data to better characterize the risk, revising the drug’s label, or requiring a risk evaluation and mitigation strategy.
Likewise, by adding a drug to the list, the FDA is not implying that clinicians should cease prescribing it or that patients should stop taking it, the agency says.
The antiemetics on the watch list belong to a subtype of serotonin blockers that bind to the 5-HT3 receptor. Clinicians prescribe them to prevent nausea and vomiting in patients undergoing chemotherapy for cancer. Serotonin syndrome, which was reported to FAERS in conjunction with these antiemetics, is caused by excessive levels of the neurotransmitter. It can be fatal. Symptoms include confusion, agitation, dilated pupils, headache, rapid heart rate, and changes in blood pressure and temperature.
The other drug on the latest watch list, metoprolol succinate, is used to treat angina, heart failure, and hypertension.
Potential Signals of Serious Risks/New Safety Information Identified by FAERS, January 2013 to March 2013
Our coursework focuses on key critical-thinking and leadership skills.
Information from Industry
| Product name: active ingredient (trade) or product class |
Potential signal of a serious risk/new safety information |
Additional information (as of May 1, 2013) |
| Metoprolol succinate (Toprol-XL, AstraZeneca) extended-release products |
Lack of therapeutic effect, possibly related to product quality issues |
FDA is continuing to evaluate this issue to determine the need for any regulatory action. |
| Serotonin-3 (5-HT3) receptor antagonist products: ondansetron(Zofran, GlaxoSmithKline, andZuplenz, Par Pharmaceutical), palonosetron (Aloxi, Helsinn Healthcare), granisetron (Kytril, Hoffmann-La Roche) |
Serotonin syndrome |
FDA is continuing to evaluate this issue to determine the need for any regulatory action. |
SOURCE
http://www.medscape.com/viewarticle/806890
More information on FAERS and its quarterly watch list is available on the FDA Web site.
Potential Signals of Serious Risks/New Safety Information Identified by FAERS, January 2013 to March 2013
http://www.medscape.com/viewarticle/806890
Carvedilol superior to Metoprolol in MADIT-CRT analysis
APRIL 2, 2013 Michael O’Riorda
The benefit of carvedilol over metoprolol was more pronounced in the subgroup of patients with a cardiac resynchronization therapy defibrillator (CRT-D), where carvedilol was associated with a significant 39% reduction in the risk of hospitalization for HF or death, and in those with left bundle branch block (LBBB). In the LBBB patients with a CRT-D, treatment with carvedilol was associated with a 49% reduction in risk compared with metoprolol.
“Furthermore, we found a pronounced dosage-dependent relationship between outcome and dose in carvedilol, which was not found in metoprolol-treated patients,” write Dr Martin Ruwald (University of Rochester Medical Center, New York) and colleagues in the April 1, 2013 issue of the Journal of the American College of Cardiology.
Benefit follows results observed in COMET
The MADIT-CRT study was presented and published in 2009 and included patients with mild HF or left ventricular dysfunction without symptoms. Participants in the trial had NYHA class 1 and 2 disease, systolic dysfunction, and ventricular dyssynchrony (wide QRS complexes). As reported by heartwire, the study showed that the addition of resynchronization pacing in primary-prevention patients with an implantable cardioverter defibrillator (ICD) reduced the risk of HF events by approximately one-third over 2.5 years.
Both metoprolol and carvedilol have a class IA indication in the management of patients with HF, with choice of the drug left to the discretion of the physician. In the Carvedilol or Metoprolol European Trial (COMET), there was an absolute 5.7% survival benefit with carvedilol over metoprolol. Other studies and analyses have suggested that there are differences between the two beta-blockers, say Ruwald and colleagues.
In this analysis of MADIT-CRT, which included 1515 patients with left ventricular ejection fraction (LVEF)<30%, QRS duration >130 ms, and NYHA functional class 1 or 2, the primary end point of hospitalization for HF or death from any cause occurred in 132 patients (30%) taking metoprolol and 243 patients (23%) taking carvedilol. During the 3.4-year follow-up, 48 patients (11%) taking metoprolol and 104 patients (10%) taking carvedilol died.
In multivariate analysis, the reduction in the primary end point with carvedilol translated into a 30% reduction in risk compared with metoprolol, a benefit that was driven primarily by a reduction in HF hospitalizations. There was only a trend toward a reduction in the risk of ventricular tachycardia/ventricular fibrillation (VT/VF). The reduction in the risk of hospitalization for HF/death from any cause was more pronounced in patients receiving CRT-Ds.
Reduction in HF hospitalization/death (carvedilol vs metoprolol)
| Study population and subgroups |
Hazard ratio (95% CI) |
| MADIT-CRT |
0.70 (0.57-0.87) |
| CRT-D |
0.61 (0.46-0.82) |
| ICD |
0.81 (0.59-1.11) |
| CRT-D and LBBB |
0.51 (0.35-0.76) |
| CRT and non-LBBB |
0.79 (0.51-1.23) |
| ICD and LBBB |
0.96 (0.66-1.39) |
| ICD and non-LBBB |
0.55 (0.30-1.00) |
| LBBB |
0.73 (0.56-0.95) |
| Non-LBBB |
0.64 (0.45-0.91) |
The researchers note that mean carvedilol and metoprolol doses in MADIT-CRT were 18 mg and 64 mg, respectively. These dosages are comparable to real-life dosages administered to patients in the clinical setting, although somewhat lower than in previous randomized controlled trials, according to the researchers.
“We speculate that low baseline resting heart rates in our study indicate that the patients generally were well titrated at baseline and that the rate may have contributed to a relatively low dose in both metoprolol and carvedilol compared with the beta-blocker dosage in clinical trials,” state Ruwald et al.
http://www.theheart.org/article/1524745.do
Effect of metoprolol versus carvedilol on outcomes in MADIT-CRT (multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy).
Ruwald MH, Ruwald AC, Jons C, Alexis J, McNitt S, Zareba W, Moss AJ.
Source
Heart Research Follow-up Program, Cardiology Division, University of Rochester Medical Center, Rochester, NY 14642, USA. mruwald@hotmail.com
Abstract
OBJECTIVES:
This study sought to compare the effects of metoprolol and carvedilol in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) study.
BACKGROUND:
The impact of beta-blockers in heart failure (HF) patients with devices is uninvestigated.
METHODS:
All patients receiving either metoprolol or carvedilol in the MADIT-CRT study were identified and compared. Time-dependent Cox proportional hazard regression analyses were performed to assess differences in hospitalization for HF or death and ventricular arrhythmias.
RESULTS:
Hospitalization for HF or death occurred in 30% of the patients on metoprolol and in 23% on carvedilol. Treatment with carvedilol was associated with a significantly decreased risk of hospitalization for HF or death when compared with metoprolol (hazard ratio [HR]: 0.70, [95% confidence interval (CI): 0.57 to 0.87], p = 0.001). This reduction in risk was further attenuated in the subgroup of cardiac resynchronization therapy with implantable cardioverter-defibrillator (CRT-D) patients (HR: 0.61 [95% CI: 0.46 to 0.82], p = 0.001) and CRT-D patients with left bundle branch block (LBBB) (HR: 0.51 [95% CI: 0.35 to 0.76], p < 0.001). Ventricular arrhythmias occurred in 26% and in 22%, respectively, of the patients receiving metoprolol or carvedilol (HR: 0.80 [95% CI: 0.63 to 1.00], p = 0.050). General use of beta-blockers and adherence in this study was high, and a clear dose-dependent relationship was found in carvedilol, but not in metoprolol.
CONCLUSIONS:
In HF patients in New York Heart Association functional class I and II and with wide QRS complexes, carvedilol was associated with a 30% reduction in hospitalizations for HF or death when compared with metoprolol. A novel beneficial and synergistic effect of carvedilol was seen in patients with CRT-D and LBBB. Furthermore, we found a pronounced dose-dependent relationship in carvedilol, but not in metoprolol.
http://www.ncbi.nlm.nih.gov/pubmed/23500269?dopt=Abstract
Extended-Release Metoprolol ( Toprol-XL) Must Be Combined With Alpha-Blocker in Pheochromocytoma
On February 12, the FDA approved safety labeling revisions for metoprolol succinate (Toprol-XL extended-release tablets; AstraZeneca LP) to provide recommendations regarding its use in the setting of pheochromocytoma.
Patients diagnosed with pheochromocytoma should only receive extended-release metoprolol in combination with an alpha-blocker and only after alpha-blocker therapy has been initiated. Administration of beta-blockers alone in this setting has been linked to a paradoxic increase in blood pressure because of the attenuation of beta-mediated vasodilation in skeletal muscle.
Metoprolol is a beta 1-selective (cardioselective) adrenoceptor-blocking agent indicated for the treatment of hypertension; angina pectoris; and stable, symptomatic heart failure of ischemic, hypertensive, or cardiomyopathic origin.
http://www.medscape.com/viewarticle/591151
Study Suggests Benefit For Beta Blockers During Noncardiac Surgery
The use of perioperative beta-blockade for noncardiac surgery has been declining as a result of the controversial POISE study, which turned up evidence for harm associated with extended-release metoprolol in this setting. Now a large new observational study published in JAMA offers a contrary perspective by suggesting that perioperative beta-blockade may be beneficial in low- to intermediate-risk patients. But without better evidence the debate about this topic is unlikely to be resolved. Martin London and colleagues performed a retrospective analysis of 136,745 patients who underwent noncardiac surgery at VA hospitals, 40…
Source: CardioBrief – April 23, 2013 Category: Cardiology Authors: Larry Husten Tags: Interventional Cardiology & Surgery Prevention, Epidemiology & Outcomes beta blockers JAMA Observational study Source Type: blogs
http://www.medworm.com/rss/search.php?t=Toprol&f=drugs&blogs=1
NDA 19-962/S-038 Page 3 Rx only
TOPROL-XL®
(metoprolol succinate)
EXTENDED-RELEASE TABLETS TABLETS: 25 MG, 50 MG, 100 MG, AND 200 MG
DESCRIPTION
TOPROL-XL, metoprolol succinate, is a beta1-selective (cardioselective) adrenoceptor blocking agent, for oral administration, available as extended release tablets. TOPROL-XL has been formulated to provide a controlled and predictable release of metoprolol for once-daily administration. The tablets comprise a multiple unit system containing metoprolol succinate in a multitude of controlled release pellets. Each pellet acts as a separate drug delivery unit and is designed to deliver metoprolol continuously over the dosage interval. The tablets contain 23.75, 47.5, 95 and 190 mg of metoprolol succinate equivalent to 25, 50, 100 and 200 mg of metoprolol tartrate, USP, respectively. Its chemical name is (±)1-(isopropylamino)-3-[p-(2-methoxyethyl) phenoxy]-2-propanol succinate (2:1) (salt). Its structural formula is:
Metoprolol succinate is a white crystalline powder with a molecular weight of 652.8. It is freely soluble in water; soluble in methanol; sparingly soluble in ethanol; slightly soluble in dichloromethane and 2-propanol; practically insoluble in ethyl-acetate, acetone, diethylether and heptane. Inactive ingredients: silicon dioxide, cellulose compounds, sodium stearyl fumarate, polyethylene glycol, titanium dioxide, paraffin.
CLINICAL PHARMACOLOGY General
Metoprolol is a beta1-selective (cardioselective) adrenergic receptor blocking agent. This preferential effect is not absolute, however, and at higher plasma concentrations, metoprolol also inhibits beta2adrenoreceptors, chiefly located in the bronchial and vascular musculature. Metoprolol has no intrinsic sympathomimetic activity, and membrane-stabilizing activity is detectable only at plasma concentrations much greater than required for beta-blockade. Animal and human experiments indicate that metoprolol slows the sinus rate and decreases AV nodal conduction.
Clinical pharmacology studies have confirmed the beta-blocking activity of metoprolol in man, as shown by (1) reduction in heart rate and cardiac output at rest and upon exercise, (2) reduction of systolic blood pressure upon exercise, (3) inhibition of isoproterenol-induced tachycardia, and (4) reduction of reflex orthostatic tachycardia. NDA 19-962/S-038 Page 4
The relative beta1-selectivity of metoprolol has been confirmed by the following: (1) In normal subjects, metoprolol is unable to reverse the beta2-mediated vasodilating effects of epinephrine. This contrasts with the effect of nonselective beta-blockers, which completely reverse the vasodilating effects of epinephrine. (2) In asthmatic patients, metoprolol reduces FEV1 and FVC significantly less than a nonselective beta-blocker, propranolol, at equivalent beta1-receptor blocking doses.
In five controlled studies in normal healthy subjects, the same daily doses of TOPROL-XL and immediate release metoprolol were compared in terms of the extent and duration of beta1-blockade produced. Both formulations were given in a dose range equivalent to 100-400 mg of immediate release metoprolol per day. In these studies, TOPROL-XL was administered once a day and immediate release metoprolol was administered once to four times a day. A sixth controlled study compared the beta1-blocking effects of a 50 mg daily dose of the two formulations. In each study, beta1-blockade was expressed as the percent change from baseline in exercise heart rate following standardized submaximal exercise tolerance tests at steady state. TOPROL-XL administered once a day, and immediate release metoprolol administered once to four times a day, provided comparable total beta1blockade over 24 hours (area under the beta1-blockade versus time curve) in the dose range 100–400 mg. At a dosage of 50 mg once daily, TOPROL-XL produced significantly higher total beta1-blockade over 24 hours than immediate release metoprolol. For TOPROL-XL, the percent reduction in exercise heart rate was relatively stable throughout the entire dosage interval and the level of beta1-blockade increased with increasing doses from 50 to 300 mg daily. The effects at peak/trough (ie, at 24-hours post-dosing) were: 14/9, 16/10, 24/14, 27/22 and 27/20% reduction in exercise heart rate for doses of 50, 100, 200, 300 and 400 mg TOPROL-XL once a day, respectively. In contrast to TOPROL-XL, immediate release metoprolol given at a dose of 50–100 mg once a day produced a significantly larger peak effect on exercise tachycardia, but the effect was not evident at 24 hours. To match the peak to trough ratio obtained with TOPROL-XL over the dosing range of 200 to 400 mg, a t.i.d. to q.i.d. divided dosing regimen was required for immediate release metoprolol. A controlled cross-over study in heart failure patients compared the plasma concentrations and beta1-blocking effects of 50 mg immediate release metoprolol administered t.i.d., 100 mg and 200 mg TOPROL-XL once daily. A 50 mg dose of immediate release metoprolol t.i.d. produced a peak plasma level of metoprolol similar to the peak level observed with 200 mg of TOPROL-XL. A 200 mg dose of TOPROL-XL produced a larger effect on suppression of exercise-induced and Holter-monitored heart rate over 24 hours compared to 50 mg t.i.d. of immediate release metoprolol.
The relationship between plasma metoprolol levels and reduction in exercise heart rate is independent of the pharmaceutical formulation. Using an Emax model, the maximum effect is a 30% reduction in exercise heart rate, which is attributed to beta1-blockade. Beta1-blocking effects in the range of 30– 80% of the maximal effect (approximately 8–23% reduction in exercise heart rate) correspond to metoprolol plasma concentrations from 30-540 nmol/L. The relative beta1-selectivity of metoprolol diminishes and blockade of beta2-adrenoceptors increases at plasma concentrations above 300 nmol/L.
Although beta-adrenergic receptor blockade is useful in the treatment of angina, hypertension, and heart failure there are situations in which sympathetic stimulation is vital. In patients with severely damaged hearts, adequate ventricular function may depend on sympathetic drive. In the presence of AV block, beta-blockade may prevent the necessary facilitating effect of sympathetic activity on conduction. Beta2-adrenergic blockade results in passive bronchial constriction by interfering with endogenous adrenergic bronchodilator activity in patients subject to bronchospasm and may also interfere with exogenous bronchodilators in such patients. NDA 19-962/S-038 Page 5
In other studies, treatment with TOPROL-XL produced an improvement in left ventricular ejection fraction. TOPROL-XL was also shown to delay the increase in left ventricular end-systolic and end-diastolic volumes after 6 months of treatment.
Pharmacokinetics
Adults In man, absorption of metoprolol is rapid and complete. Plasma levels following oral administration of conventional metoprolol tablets, however, approximate 50% of levels following intravenous administration, indicating about 50% first-pass metabolism. Metoprolol crosses the blood-brain barrier and has been reported in the CSF in a concentration 78% of the simultaneous plasma concentration.
Plasma levels achieved are highly variable after oral administration. Only a small fraction of the drug (about 12%) is bound to human serum albumin. Metoprolol is a racemic mixture of R- and S- enantiomers, and is primarily metabolized by CYP2D6. When administered orally, it exhibits stereoselective metabolism that is dependent on oxidation phenotype. Elimination is mainly by biotransformation in the liver, and the plasma half-life ranges from approximately 3 to 7 hours. Less than 5% of an oral dose of metoprolol is recovered unchanged in the urine; the rest is excreted by the kidneys as metabolites that appear to have no beta-blocking activity. Following intravenous administration of metoprolol, the urinary recovery of unchanged drug is approximately 10%. The systemic availability and half-life of metoprolol in patients with renal failure do not differ to a clinically significant degree from those in normal subjects. Consequently, no reduction in dosage is usually needed in patients with chronic renal failure.
Metoprolol is metabolized predominantly by CYP2D6, an enzyme that is absent in about 8% of Caucasians (poor metabolizers) and about 2% of most other populations. CYP2D6 can be inhibited by a number of drugs. Concomitant use of inhibiting drugs in poor metabolizers will increase blood levels of metoprolol several-fold, decreasing metoprolol’s cardioselectivity. (See PRECAUTIONS, Drug Interactions.)
In comparison to conventional metoprolol, the plasma metoprolol levels following administration of TOPROL-XL are characterized by lower peaks, longer time to peak and significantly lower peak to trough variation. The peak plasma levels following once-daily administration of TOPROL-XL average one-fourth to one-half the peak plasma levels obtained following a corresponding dose of conventional metoprolol, administered once daily or in divided doses. At steady state the average bioavailability of metoprolol following administration of TOPROL-XL, across the dosage range of 50 to 400 mg once daily, was 77% relative to the corresponding single or divided doses of conventional metoprolol. Nevertheless, over the 24-hour dosing interval, ß1-blockade is comparable and dose-related (see CLINICAL PHARMACOLOGY). The bioavailability of metoprolol shows a dose-related, although not directly proportional, increase with dose and is not significantly affected by food following TOPROL-XL administration.
Pediatrics The pharmacokinetic profile of TOPROL-XL was studied in 120 pediatric hypertensive patients (6-17 years of age) receiving doses ranging from 12.5 to 200 mg once daily. The pharmacokinetics of metoprolol were similar to those described previously in adults. Age, gender, race, and ideal body weight had no significant effects on metoprolol pharmacokinetics. Metoprolol apparent oral clearance (CL/F) increased linearly with body weight. Metoprolol pharmacokinetics have not been investigated in patients < 6 years of age. NDA 19-962/S-038 Page 6
Hypertension
The mechanism of the antihypertensive effects of beta-blocking agents has not been elucidated. However, several possible mechanisms have been proposed: (1) competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac output; (2) a central effect leading to reduced sympathetic outflow to the periphery; and
(3) suppression of renin activity.
Clinical Trials
In a double-blind study, 1092 patients with mild-to-moderate hypertension were randomized to once daily TOPROL-XL (25, 100, or 400 mg), PLENDIL® (felodipine extended release tablets), the combination, or placebo. After 9 weeks, TOPROL-XL alone decreased sitting blood pressure by 6-8/47 mmHg (placebo-corrected change from baseline) at 24 hours post-dose. The combination of TOPROL-XL with PLENDIL has greater effects on blood pressure.
In controlled clinical studies, an immediate release dosage form of metoprolol was an effective antihypertensive agent when used alone or as concomitant therapy with thiazide-type diuretics at dosages of 100-450 mg daily. TOPROL-XL, in dosages of 100 to 400 mg once daily, produces similar ß1-blockade as conventional metoprolol tablets administered two to four times daily. In addition, TOPROL-XL administered at a dose of 50 mg once daily lowered blood pressure 24-hours post-dosing in placebo-controlled studies. In controlled, comparative, clinical studies, immediate release metoprolol appeared comparable as an antihypertensive agent to propranolol, methyldopa, and thiazide-type diuretics, and affected both supine and standing blood pressure. Because of variable plasma levels attained with a given dose and lack of a consistent relationship of antihypertensive activity to drug plasma concentration, selection of proper dosage requires individual titration.
Angina Pectoris
By blocking catecholamine-induced increases in heart rate, in velocity and extent of myocardial contraction, and in blood pressure, metoprolol reduces the oxygen requirements of the heart at any given level of effort, thus making it useful in the long-term management of angina pectoris.
Clinical Trials
In controlled clinical trials, an immediate release formulation of metoprolol has been shown to be an effective antianginal agent, reducing the number of angina attacks and increasing exercise tolerance. The dosage used in these studies ranged from 100 to 400 mg daily. TOPROL-XL, in dosages of 100 to 400 mg once daily, has been shown to possess beta-blockade similar to conventional metoprolol tablets administered two to four times daily.
Heart Failure
The precise mechanism for the beneficial effects of beta-blockers in heart failure has not been elucidated. NDA 19-962/S-038 Page 7
Clinical Trials
MERIT-HF was a double-blind, placebo-controlled study of TOPROL-XL conducted in 14 countries including the US. It randomized 3991 patients (1990 to TOPROL-XL) with ejection fraction ≤ 0.40 and NYHA Class II-IV heart failure attributable to ischemia, hypertension, or cardiomyopathy. The protocol excluded patients with contraindications to beta-blocker use, those expected to undergo heart surgery, and those within 28 days of myocardial infarction or unstable angina. The primary endpoints of the trial were (1) all-cause mortality plus all-cause hospitalization (time to first event) and
(2) all-cause mortality. Patients were stabilized on optimal concomitant therapy for heart failure, including diuretics, ACE inhibitors, cardiac glycosides, and nitrates. At randomization, 41% of patients were NYHA Class II, 55% NYHA Class III; 65% of patients had heart failure attributed to ischemic heart disease; 44% had a history of hypertension; 25% had diabetes mellitus; 48% had a history of myocardial infarction. Among patients in the trial, 90% were on diuretics, 89% were on ACE inhibitors, 64% were on digitalis, 27% were on a lipid-lowering agent, 37% were on an oral anticoagulant, and the mean ejection fraction was 0.28. The mean duration of follow-up was one year. At the end of the study, the mean daily dose of TOPROL-XL was 159 mg.
The trial was terminated early for a statistically significant reduction in all-cause mortality (34%, nominal p= 0.00009). The risk of all-cause mortality plus all-cause hospitalization was reduced by 19% (p= 0.00012). The trial also showed improvements in heart failure-related mortality and heart failure-related hospitalizations, and NYHA functional class.
The table below shows the principal results for the overall study population. The figure below illustrates principal results for a wide variety of subgroup comparisons, including US vs. non-US populations (the latter of which was not pre-specified). The combined endpoints of all-cause mortality plus all-cause hospitalization and of mortality plus heart failure hospitalization showed consistent effects in the overall study population and the subgroups, including women and the US population. However, in the US subgroup (n=1071) and women (n=898), overall mortality and cardiovascular mortality appeared less affected. Analyses of female and US patients were carried out because they each represented about 25% of the overall population. Nonetheless, subgroup analyses can be difficult to interpret and it is not known whether these represent true differences or chance effects.
SOURCE
http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019962s038lbl.pdf
Clinical Endpoints in the MERIT-HF Study
| CLINICAL ENDPOINT |
NUMBER OF PATIENTS |
RELATIVE RISK (95% CI) |
RISK REDUCTION WITH TOPROLXL |
NOMINAL P-VALUE |
| PLACEBO N=2001 |
TOPROLXL N=1990 |
| ALL-CAUSE MORTALITY PLUS ALL-CAUSE HOSPITALIZATION* |
767 |
641 |
0.81 (0.730.90) |
19% |
0.00012 |
Last week I moderated a panel called “The New Rules of Partnerships and Collaborations” at the Convergence East conference on Cape Cod, and the experience gave me a chance to probe some of the biopharma industry’s top dealmakers about their preferences and prejudices going into talks with other companies. I’ve decided to write down three key observations or “rules” that emerged during the panel and other notes from the Convergence meeting.
2012pharmaceutical
Amandeep Kaur
Aashir Awan, Phd
Abhisar Anand
Adina Hazan
Alan F. Kaul, PharmD., MS, MBA, FCCP
alexcrystal6
anamikasarkar
apreconasia
aviralvatsa
David Orchard-Webb, PhD
danutdaagmailcom
Demet Sag, Ph.D., CRA, GCP
Dror Nir
dsmolyar
Ethan Coomber
evelinacohn
Gail S Thornton
Irina Robu
jayzmit48
jdpmd
jshertok
kellyperlman
Ed Kislauskis
larryhbern
Madison Davis
marzankhan
megbaker58
ofermar2020
Dr. Pati
pkandala
ritusaxena
Rick Mandahl
sjwilliamspa
Srinivas Sriram
stuartlpbi
Dr. Sudipta Saha
tildabarliya
vaishnavee24
zraviv06
zs22