As direct outcomes on health are hard to measure, we estimated the effects by studying all cause mortality using a newly developed health impact model to integrate recently developed tools, existing data from scientific studies, and local data.
For example, the relevant direct outcome for the question on the effectiveness of chemoprophylaxis before hospital discharge in preventing further cases among contacts (Question A) would be the incidence of subsequent cases in household contacts of the IMD patients who received antibiotics prior to discharge from hospital.
In a recent German trial, internet based data sampling showed an additional response bias but had no direct effect on outcome scales [ 38].
HU remains a standard cytoreduction therapy in PV, and it is important to recognize that HU resistance increases both LT and MF transformation risk (HR 6.8; 95% CI, 3.0 15.4%, P<0.001), whereas HU intolerance has no direct effect on outcomes.
Although the necessity for mediation of a direct effect on outcomes has since been questioned (criterion 3 [ 20, 32]), Baron and Kenny's [ 31] causal steps framework is still the most widely used approach to testing mediation in the social sciences [ 33].
In other words, the instrument neither has a direct effect on the outcome variable nor is it related to the outcome through a channel other than the endogenous regressor.
If a relationship is causal, and the gene is not having a direct effect on the outcome, a relationship will be seen between the genotype and outcome only in smokers and not in non-smokers, as the gene will not influence smoking among those who have never started smoking.
Although the proxy gene identified only affects the outcome via the behaviour or exposure of interest, if a linked gene has a direct effect on the outcome, it may be this driving any association found, rather than the exposure.
The possibility of the variant having a direct effect on the outcome of interest can be tested directly – if the variant has a direct effect on the outcome, there will be a relationship between genotype and outcome in non-smokers.
The few hours the Jets spent playing Skee-Ball and Pop-A-Shot had no direct effect on the outcome Sunday, a 37-14 loss to Buffalo in the swirling wind at Ralph Wilson Stadium.
