In our 31st episode we offer an approach to new drugs. We look at the last five years of new product introduction and consider the frequency of new drugs being truly novel and a substantial addition. We examine how medicines termed “new” are frequently modifications that make no measurable change in the product. Finally, we consider a basic approach to new products. James gets militant on the theme (but not the message) while Mike runs for cover.

Show Notes

1) Number of drugs considered to be a “substantial” improvement – 2001 to 2007 – category 2 is considered substantial improvement (14 out of 147) PMPRB 2007 Annual report

2) Prescrire review of new drugs Can J Clin Pharmacol 2005;12:e10-e21

3) Drugs withdrawn from the Canadian market for safety reasons CMAJ 2005;172:765–7

4) Guideline recommendations are not necessarily based on “solid” evidence and are often opinion-based Example – Canadian Cardiovascular Society position statement – Recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease

Can J Cardiol 2006;22:913-927

Of the 15 specific recommendations in this document:

4 were considered Level A – Data derived from multiple randomized controlled trials or meta-analyses

0 were considered Level B – Data derived from a single randomized controlled trial or large, nonrandomized studies

11 were considered Level C – Consensus of opinion by experts and/or small studies, retrospective studies or registries

The topic for our 30th episode is stolen from the headlines. We look at the much publicized Jupiter trial of C-Reactive Protein (CRP) and the use of a statin. We review the details, strengths and weakness of the trial. From there we look at related questions of risk assessment with CRP, reducing CRP and the uncertainty in the lipid hypothesis. We end by concluding that although trust in mechanisms and theories can lead to poor decisions they are generally less confusing than our podcasts.

Show Notes

1) Jupiter – statins, lipids and CRP

NEJM 2008;359:2195-207

2) Knowing CRP doesn’t change estimation of cardiovascular risk

NEJM 2006;355:2631-9

Arch Intern Med 2006;166:1368-73

3) Web site calculator that uses CRP

Reynolds Risk Score

4) Ezetrol Study (reduces CRP but no other change)

N Engl J Med 2008;358:1431-43.

5) Mechanistic mistaken thinking Beta-blockers in CHF

Arch Intern Med 2002;162:641-8

Anti-oxidant studies

Lancet 2002;360:23-33

Lancet 2003;361:2017-23.

Atenolol for BP but not for outcomes

Lancet 2004;364:1684-9

In Episode 29, we review questions around informed decision-making, risk-benefits of statins across different populations (women, chronic kidney disease, etc), and comparisons of calculated risks and trial results. We also talk about prescribing of new antimicrobials, differentiating typical from atypical pneumonias and then attempt to clarify a few trials including HOPE. James desperately searches for pearls among Mike’s explanations of the uncertainty and gaps in the research.

Show Notes

1) The HOPE trial

NEJM 2000;342:145–53

2) HOPE was actually more like a blood pressure trial than originally thought – 24 hour blood pressure differences between the 2 groups were 10/4 mmHg

Hypertension 2001;38;e28-e32

4) Meta-analysis of statins in patients with chronic kidney disease

BMJ 2008;336:645-51

5) Meta-analysis CMAJ on high vs low dose statin in secondary prevention

CMAJ 2008;178:576-84

6) Mediterranean diet – no difference between the groups in weight, cholesterol or blood pressure at the end of the study but cardiovascular events were reduced

Lancet 1994;343:1454-9

7) ACCORD and ADVANCE trials

Podcast #9

8)UKPDS (recent results)

NEJM 2008;359:1577-89

9) BP trial for patients over age 80

NEJM 2008;358:1887-98

In Episode 28, we review questions around osteoporosis including: bone density testing and the limits of medical tests in general; the risks (including osteoporosis) and benefits of proton pump inhibitors for heartburn; and assessing calcium intake and the possible risks of calcium. We also briefly discuss topics of risk assessors of CVD, an approach to patients using complementary alternative therapies, and make a few random, but obviously brilliant suggestions.

Show Notes

1) Comparison of H2 Blocker vs PPI

CADTH report on the Evidence for PPI Use in GERD

2) Studies suggesting risk from PPI for osteoporosis/fracture and C. difficile CMAJ 2008;179:319-26 JAMA 2005;294:2989-95.

3) Calcium and vascular events BMJ 2008;336:262-6 Circulation 2007;115:846-54

4) STENO – multifactorial intervention for type 2 diabetes N Engl J Med 2008;358:580-91

5) The book The Bedford Murder: An Evidence-Based Clinical Mystery (Paperback) by Marshall Godwin & Geoffrey Hodgetts