8/20/2019 Tutorial about Hazard Ratios - Students 4 Best Evidence

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Tutorial about Hazard Ratios

Posted on April 5, 2016 by Loai Albarqouni

Tutorials and Fundamentals

You have been asked to run a journal club in your department about heart failure. You followed the key steps of Evidence-Based

Practice that you have learned: formulated a clear searchable clinical question, searched the main databases and came across
this recent hypothetical article.

In this hypothetical article, the authors conducted a randomised controlled trial to investigate the e ectiveness of a new treatment for

improving the survival of patients with heart failure. A total of 105 patients were randomised to the treatment group and a total of

106 were randomised to the control group. The primary outcome was the overall survival rate.

The main result of this trial can be summarised in this paragraph: “After a median follow-up of 1500 days, the hazard ratio for death in the

treatment group, 0.38; 95% con dence interval [CI], 0.28 to 0.53; P<0.0001).”

In addition, the authors presented the gure below summarizing their main results:

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Figure produced by the author using R software

(Blue line represents treatment group and green line represents control group).

You want to critically appraise the article. However, you have some di culty understanding its main results and have a few
questions:

What is Hazard Ratio? What do the authors mean by 95% con dence interval? How can you interpret this information?

How can I read the gure? What are the main ndings I can learn from this gure?

How can I convey this information to my patients?

In this blog, you may nd the answers to these questions.

What is a Hazard Ratio & what are Confidence Intervals?

Hazard ratio (HR) is a measure of an e ect of an intervention on an outcome of interest over time. Hazard ratio is reported most
commonly in time-to-event analysis or survival analysis (i.e. when we are interested in knowing how long it takes for a

particular event/outcome to occur).

The outcome could be an adverse/negative outcome (e.g. time from treatment/surgery until death/relapse) or a positive outcome (e.g.

time to cure/discharge/conceive/heal or disease-free survival).

Hazard Ratio (i.e. the ratio of hazards) = Hazard in the intervention group ÷ Hazard in the control group

Hazard represents the instantaneous event rate, which means the probability that an individual would experience an event (e.g.

death/relapse) at a particular given point in time after the intervention, assuming that this individual has survived to that particular point
of time without experiencing any event.

Con dence Interval (CI): is the range of values that is likely to include the true population value and is used to measure the precision of
the study’s estimate (in this case, the precision of the Hazard Ratio). The narrower the con dence interval, the more precise the estimate.

(Precision will be a ected by the study’s sample size). If the con dence interval includes 1, then the hazard ratio is not signi cant.

Interpretation of Hazard Ratio

Because Hazard Ratio is a ratio, then when:

HR = 0.5: at any particular time, half as many patients in the treatment group are experiencing an event compared to the control group.

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HR = 1: at any particular time, event rates are the same in both groups,
HR = 2: at any particular time, twice as many patients in the treatment group are experiencing an event compared to the control group.

Applying this to our hypothetical study results:

In the results, the authors reported that the hazard ratio for death with the new treatment = 0.38 (95% CI, 0.28-0.53; P<0.0001). What does

that mean?
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Patients in the new treatment group at any time point during the study period were 62% less likely to die than patients in the control group, and we
are 95% con dent that the true value is lying between 47%-72%. (i.e. we are 95% sure that patients in the new treatment group were between 47%

and 72% less likely to die than patients in the control group). 

Kaplan-Meier curve (or Survival curve)

Figure produced by the author using R software

(Blue line represents treatment group and green line represents control group).

Kaplan-Meier curve: is a graphical method of displaying survival data or time-to-event analysis (i.e. the proportion of patents surviving

against time) and is usually drawn as a step function.

The horizontal axis represents the time of follow-up starting from enrolment while the vertical axis represents the estimated probability

of survival.

Each downward step in the lines represents an event (the outcome of interest, e.g. death) experienced by a patient in that corresponding
group, while each small vertical tick represents a censored observation (i.e. a patient who did not experience the event of interest by the

last follow-up. This can be due to being lost to follow-up, the study period ending without an event or because the patient died from an

unrelated cause).

The numbers of patients at risk at regular time intervals is shown at the bottom of the gure. With time, fewer people remaining are at

risk.

This graph also allows you to detect the progression of the condition (e.g. early postoperative mortality or a serious adverse event
caused by the drug), by the presence of a notable sudden steep drop in survival at a particular time point.

Interpretation of this figure

The results of this graph can be communicated in various ways:

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Median survival: half of the patients in the treatment group have survived for 2246 days (median survival rate) compared to 906 days in

the control group.

Di erence in median survival: On average, patients in the intervention group survived for 1340 days longer than patients in the control

group (2246 – 906 days).

Proportion surviving at a speci c time point: about 45% of patients in the treatment group have survived for 10 years (3650 days, i.e. 10-
year survival rate). Another way of saying this is that about 45% of the patients in the treatment group have not experienced the
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Hazard Ratios vs. Risk Ratios (or Relative Risk)

Hazard ratio is frequently interpreted as risk ratio (or relative risk), but they are not technically the same. However, if that helps you to

understand hazard ratio then it is OK.  But keep in mind HR is not RR.

One of the main di erences between risk ratio and hazard ratio is that risk ratio does not care about the timing of the event but only about

the occurrence of the event by the end of the study (i.e. whether they occurred or not: the total number of events by the end of the study

period). In contrast, hazard ratio takes account not only of the total number of events, but also of the timing of each event.

References & Further Reading

1. Altman D.G., Bland J.M. Time to event (survival) data. BMJ 1998; 317:468

2. Bland J.M., Altman D.G. Survival probabilities (the Kaplan-Meier method). BMJ 1998;317:1572

3. Spruance S.L., Reid J.E., Grace M., Samore M. Hazard ratio in clinical trials. Antimicrob Agents Chemother 2004; 48: 2787–2792.

4. Sedgwick P. How to read a Kaplan-Meier survival plot. BMJ 2014; 349: g5608

5. Sedgwick P. Hazards and hazard ratios. BMJ 2012; 345: e5980

Tags:

critical appraisal epidemiology evidence hazard ratio hazard ratios interpreting patients

research risk statistics

Loai Albarqouni
Hi, I am Loai Albarqouni, a Ph.D. candidate at the Center for Research in Evidence-Based Practice, Bond University, Australia. Before, I

completed my medical degree (MD) at AlQuds University and a masters degree in Epidemiology at Ludwig Maximilian University of
Munich.

View more posts from Loai

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26 Comments on Tutorial about Hazard Ratios

Alvaro Whittembury

I would recommend to add that the intervention reduced the risk of death by 62% (1-(0.38)*100) when

compared to the comparison group.

April 9, 2016 at 1:51 am

Reply to Alvaro

Loai Albarqouni
Sure, and i did something similar in the de nition of hazard ratio : “Patients in the new treatment group at

any time point during the study period were 62% less likely to die than patients in the control group”

April 11, 2016 at 11:34 pm

Reply to Loai

Anne Abbott
Thank you!

April 20, 2016 at 4:50 am

Reply to Anne

April

Hi Loai. Could you please clarify this statement:

we are 95% con dent that the true value is lying between 47%-72%. (i.e. we are 95% sure that patients in the

new treatment group were between 28% and 53% less likely to die than patients in the control group.

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Wouldn’t it be (i.e. we are 95% sure that patients in the new treatment group were between 47% and 72%. less

likely to die than patients in the control group?

Thanks in advance.

April 30, 2016 at 10:55 am

Reply to April
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Selena Ryan-Vig

You’re quite right. Apologies, this was a mistake in the publication process and was not Loai’s error. It has

now been amended.

May 6, 2016 at 10:19 am

Reply to Selena

MedTrial

Hi, Loai!

I have a question related to this topic, please.

I have 4 groups (let’s call them A, B, C and D) and I am given hazard ratios with con dence intervals for groups B,

C and D with A being the comparator. What I really want to do is combine A, B and C ‘s data and have that whole
group compared to group D. Possible? How?

Thanks in advance!

May 27, 2017 at 5:30 am

Reply to MedTrial

Janine Khuc

HI there, thank you for the explanation it was super helpful. If I had the average age for the treatment and
control group, would it be possible to “translate” Hazard Ratios in years of life expectancy following treatment

relative to control?

Many Thanks,

Janine

August 17, 2017 at 4:27 pm

Reply to Janine

Scott Lonning
Loai

Very nice explanation on HR. The best I’ve ever seen and much appreciated. I’m sharing with my sta !

Thank you

August 18, 2017 at 1:10 pm

Reply to Scott

Simon
I am still confused about the di erence between HR and RR. You say HR takes into account timing. Does this

mean HR is actually a function of time, HR(t)? If so, then is the reported HR basically an average at the end of the

study? Doesn’t that make a single HR number quite equivalent to Risk Ratio? Or what? Thanks

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September 25, 2017 at 6:10 pm

Reply to Simon

Gene Heyman
Hazard ratios are by de nition time-dependent and thus must change as a function of time, except in the

6 exponential case. How then can there be a single, summary hazard ratio for two di erent (non exponential)
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survival curves? Is there an agreed upon comparison time, say the median for each?

November 10, 2017 at 11:47 pm

Reply to Gene

Stace

Thank you so much for the explanation, so easy to understand, gonna share it with the whole team. Bless you!

November 15, 2017 at 7:48 am

Reply to Stace

maya

hi there
could you please tell me how to calculate CI from HR & P value in an published article?

it should be noted that i havnt any data about participants in this study.

i need it for my meta analysis article

regards

March 6, 2018 at 8:36 am

Reply to maya

Richard

ci IS .25 TO .53 tHEN WHERE IS THE 47 TO 72% COME FROM?

May 17, 2018 at 5:02 pm

Reply to Richard

Lakshmi Arangan

What does a hazard ratio of 1.75 mean?

July 9, 2018 at 1:29 pm

Reply to Lakshmi

june

Thank you !

August 6, 2018 at 2:33 pm

Reply to june

Elliot Dinetz

very informative for M.D.’s thanks

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September 5, 2018 at 4:29 am

Reply to Elliot

Ritasman Baisya

Nice explanation

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Reply to Ritasman

Silverio Cabellon, Jr.

May I commend the clarity in which you have presented Hazard Ratio.

September 21, 2018 at 11:56 pm

Reply to Silverio

Alice Chu
Thank you, thank you, thank you for explaining these complex stats so well.

October 17, 2018 at 3:55 am

Reply to Alice

Abdullah

Good stu .Thank you Loai

November 19, 2018 at 9:44 pm

Reply to Abdullah

George

In case anyone is looking for a quick and easy way to calculate a hazard ratio, HR p-value and con dence

intervals, I found this free tool: https://www.gigacalculator.com/calculators/hazard-ratio-calculator.php . Real

easy to use as well, just copy & paste from a spreadsheet.

January 17, 2019 at 11:04 am

Reply to George

Funmilayo

Great topic

January 26, 2019 at 8:53 pm

Reply to Funmilayo

Omar

thank you, great tutorial

February 4, 2019 at 9:13 pm

Reply to Omar

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Cyril Spann

what about median endpoint ratio

April 1, 2019 at 8:11 am

Reply to Cyril

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Emma Carter

A comment from Twitter from Ralph Brinks (Mathematician): Thx for sharing Not 100% accurate in 2nd part
of the def “Hazard [rate] represents the instantaneous event rate, which means the probability that an individual

would experience an event”. It’s not a probability (bc can be > 1) but a limit. See Kalb eisch & Prentice – “The

Statistical Analysis of Failure Time Data”.

July 22, 2019 at 10:58 am

Reply to Emma

Akash
Hi Laoi,

Great job on explanation. Could you help me understand:

Drug A vs placebo: Stable disease in 66.7% vs 37.2% at 12 months p=0.00007 HR 0.34 (95% CI, 0.20-0.59)

How do you verbalize this data?

July 23, 2019 at 6:28 pm

Reply to Akash

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