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Understanding variation in disease risk: the elusive concept of frailty.

Aalen OO, Valberg M, Grotmol T, Tretli S - Int J Epidemiol (2014)

Bottom Line: Heterogeneity often manifests itself as clustering of cases in families more than would be expected by chance.We emphasize that apparently moderate familial relative risks can only be explained by strong underlying variation in disease risk between families and individuals.Finally, we highlight the potential impact of frailty variation in the interpretation of standard epidemiological measures such as hazard and incidence rates.

View Article: PubMed Central - PubMed

Affiliation: Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway and Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway o.o.aalen@medisin.uio.no.

No MeSH data available.


Effect of discontinuing treatment. A control group with hazard rate  is compared with a treatment group with hazard rate . Treatment is discontinued at time point 1.
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dyu192-F7: Effect of discontinuing treatment. A control group with hazard rate is compared with a treatment group with hazard rate . Treatment is discontinued at time point 1.

Mentions: Another interesting effect of frailty occurs when discontinuing treatment in a clinical trial. Let us assume that the treatment group has hazard rate and the control group has hazard rate, presuming the treatment is effective. At the start of the study, the hazard ratio is 2. Because the treatment is effective, patients in the control group will on average have events earlier than in the treatment group, and the hazard ratio will decrease with time. At some point the difference between the hazard rates is so small that it is decided treatment is no longer effective, and it is stopped. A possible consequence of this decision is that the hazard ratio drops below 1, and it appears protective to be a member of the control group (Figure 7). In the control group the frailest individuals would already have had an event at this point and, at the time of discontinuing the treatment, there would be a higher proportion of less frail individuals in the control group. In the treatment group, frail individuals that would already have had an event if they had not been treated, have a very high risk immediately after the treatment is stopped. Not being aware of a possible frailty effect may lead to a wrong impression of the effect of discontinuing a treatment for an individual.Figure 7.


Understanding variation in disease risk: the elusive concept of frailty.

Aalen OO, Valberg M, Grotmol T, Tretli S - Int J Epidemiol (2014)

Effect of discontinuing treatment. A control group with hazard rate  is compared with a treatment group with hazard rate . Treatment is discontinued at time point 1.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588855&req=5

dyu192-F7: Effect of discontinuing treatment. A control group with hazard rate is compared with a treatment group with hazard rate . Treatment is discontinued at time point 1.
Mentions: Another interesting effect of frailty occurs when discontinuing treatment in a clinical trial. Let us assume that the treatment group has hazard rate and the control group has hazard rate, presuming the treatment is effective. At the start of the study, the hazard ratio is 2. Because the treatment is effective, patients in the control group will on average have events earlier than in the treatment group, and the hazard ratio will decrease with time. At some point the difference between the hazard rates is so small that it is decided treatment is no longer effective, and it is stopped. A possible consequence of this decision is that the hazard ratio drops below 1, and it appears protective to be a member of the control group (Figure 7). In the control group the frailest individuals would already have had an event at this point and, at the time of discontinuing the treatment, there would be a higher proportion of less frail individuals in the control group. In the treatment group, frail individuals that would already have had an event if they had not been treated, have a very high risk immediately after the treatment is stopped. Not being aware of a possible frailty effect may lead to a wrong impression of the effect of discontinuing a treatment for an individual.Figure 7.

Bottom Line: Heterogeneity often manifests itself as clustering of cases in families more than would be expected by chance.We emphasize that apparently moderate familial relative risks can only be explained by strong underlying variation in disease risk between families and individuals.Finally, we highlight the potential impact of frailty variation in the interpretation of standard epidemiological measures such as hazard and incidence rates.

View Article: PubMed Central - PubMed

Affiliation: Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway and Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway o.o.aalen@medisin.uio.no.

No MeSH data available.