Evidence based practice Flashcards

Question

Consequences of ‘getting it wrong’

Answer 1

Visible - putting poison on the market Invisible - witholding lifesaving treatment

Answer 2

Introduced following thalidomide Spontaneous reports sent by healthcare professionals and patients to pharmaceutical companies Yellow card scheme Methodology for monitoring safety of all marketed medicines Primary function: To provide early warnings of unknown adverse effects of medicines Historically: problem was where to find signals Now: large databases of signals so how to identify early, relevant signals

Answer 3

Either the event was caused by the drug or not Can this be determined definitely? What is the relationship between the event and the exposure being considered? Totally linked? Partially linked? Independent?

Answer 4

Type A – drug effect Type B – patient reaction Type C – where drug increases the frequency of spontaneous disease

Answer 5

Here, a signal is defined as PRR ≥2 and chi2 ≥ 4 and ≥4 case reports ROR: lower confidence interval >1 IC: lower confidence interval > 0 EBGM ≥ 2

Answer 6

the detection, assessment and prevention of adverse drug effects in humans’ (WHO) Detection of unknown adverse events and interactions Identification of risk factors and quantification of risk for known adverse reactions Detection of increases in frequency of adverse reactions Information dissemination

Answer 7

The principles of chronic disease epidemiology applied to the area of clinical pharmacology How is the drug used? What are the predictors of use? What are the outcomes?

Answer 8

- Despite rubella causing birth defects, little consideration given to drug effects on foetus until thalidomide - One third of women using thalidomide gave birth to babies with defects, (limb, bowel, ear, eye, heart, gallbladder, uterus malformations) - 40% of thalidomide victims died before 1st birthday

Answer 9

- Animal testing: mice usually used for safety screening but later found to be insensitive to thalidomide. Now several species are used in in vivo testing - Timing of exposure: if thalidomide was taken before the 34th day OR after the 50th day then no malformations were present - Earlier exposure can lead to miscarriage; late exposure to brain damage

Answer 10

Unavoidable exposure chronic underlying conditions e.g. epilepsy acute conditions e.g. infection Inadvertent exposure ~30-50% of pregnancies are unplanned

Answer 11

- Very little is known when a medicine is first marketed about its safety when used during pregnancy - Between 2011 and 2013 the US Food and Drug Administration (FDA) approved 95 new medicines - only 3 had human pregnancy experience at the time of approval – based on prior use in other countries - In a study of 172 medicines approved by the FDA between 2000 and 20101, the teratogenic risk in human pregnancy was undetermined for 168 (97.7%). - US study found 1 in 6 pregnant women receives a prescription for a potentially teratogenic medication but only 50% receive counselling

Answer 12

- Pregnant women are often excluded from clinical trials - Preclinical animal studies are often not predictive of human risk - Not possible to assume a ‘class effect’ - Gaps in our knowledge of teratogenic mechanisms - Birth defects are rare and drug exposures can be rare - Baby is an “Innocent bystander”

Answer 13

Virtually impossible to evaluate the safety of a medicine before it is granted a licence Need to monitor pregnancy outcomes once the product is on the market Aims to collect sufficient information to allow women and their healthcare professionals to balance the risks and benefits of medication use during pregnancy

Answer 14

Developed during 1970s/early 1980s Case-control surveillance systems Recruit infants with and without congenital anomalies from hospitals or birth registries Aim to evaluate associations between medicine use and pregnancy outcomes Some still actively recruiting today

Answer 15

Point of contact for women and healthcare professionals who need advice and information regarding in-utero exposures Women who have voluntarily contacted them in search of information on the safety of a medicine they are using are recruited Valuable signal generating tool Information on large number of confounding variables

Answer 16

First registry in 1984 Observational study Aim to identify major teratogens ≥ a 10-fold increase in risk requires ~1000 enrolled pregnancies

Answer 17

Self enrolment Loss to follow-up Small numbers Slow enrolment - GSK lamotrigine pregnancy registry - took 10 years to enrol the first 1,000 pregnancies Suitable comparator group

Answer 18

Often provide representative sample Routinely recorded Exposure data recorded prospectively Internal comparator(s) Some capture pregnancy losses Sample size

Answer 19

- No OTC medicines or in-patient prescribing - Don’t know whether medicine was taken - Outcome data may lack detail/completeness and accuracy - Sample size

Answer 20

- Spontaneous losses or stillbirths might be the outcome of interest - Advances in prenatal screening mean some women who are prenatally diagnosed with a severe birth defect may opt to terminate

Answer 21

- For a relatively small number of medicines, there is now sufficient evidence to demonstrate that the product is highly teratogenic when used during pregnancy - For some individuals, however, the benefits of treatment with one of these products cannot be achieved from other products - PPPs aim to allow women of child bearing potential to use highly teratogenic products whilst ensuring they are not pregnant when they start treatment and do not become pregnant during therapy or within an appropriate time period after stopping treatment.

Answer 22

- Treatment for severe recalcitrant nodular acne - Animal studies had identified concerns that there could be potential teratogenicity - However, it has a unique efficacy with a 5 month course often resulting in a cure and it has a short half life meaning the period of risk is limited - Whilst on the market between 1982 and 1988 evidence of human teratogenicity was documented

Evidence based practice Flashcards

(46 cards)