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What is the difference between OS PFS and DFS?
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What is the difference between OS, PFS and DFS?
This article let you understand the endpoints of 6 major tumor clinical trials, also take a look at advantages and disadvantages of commonly used clinical trial endpoints.
When it comes to oncology clinical research, we have to talk about the end points of clinical trials, such as the well-known OS, PFS, ORR, DFS, TTP, TTF…different endpoints serve different research purposes.
Let us take a look at the differences and advantages and disadvantages of commonly used clinical trial endpoints.
OS: Overall survival
Defined as: the time from the start of randomization to death (for any reason).
OS is considered to be the best efficacy endpoint in cancer clinical trials, and it is the preferred endpoint when the patient’s survival can be fully assessed.
The biggest advantage is that it is convenient to record. Whether in hospital or out of hospital, there is basically no difficulty in determining the date of death of a patient. If the results of the study show a small improvement in survival, it can be considered as significant evidence of direct clinical benefit.
There are also disadvantages, and the follow-up period for large trials is longer. The 5-year survival rate is often used in clinical trials, that is, the proportion of patients who survive for more than five years after a certain tumor undergoes various comprehensive treatments.
After treatment, some tumor patients recurred and metastasized, some died, and some survived. 80% of recurrence and metastasis usually occur within 3 years after radical surgery, and about 10% occur within 5 years.
The probability of recurrence after 5 years is very low. Therefore, taking 5 years as the node, this is somewhat scientific.
Of course, three-year survival rate and ten-year survival rate are also used to express curative effects.
Except for OS, all other endpoints are based on tumor measurements.
Different tumor trials have large differences in the accuracy of tumor measurement, which requires researchers to fully evaluate the benefits and biases.
If the clinical trial endpoint based on tumor measurement is used as the only evidence of effectiveness in the drug marketing application, then it should usually provide conclusive evidence from the second trial.
ORR: Objective response rate
It is defined as: the proportion of patients whose tumor volume has shrunk to a predetermined value and can maintain the minimum time limit, which is the sum of the proportion of complete remission and partial remission.
The remission period usually refers to the period from the onset of efficacy to the confirmation of tumor progression. ORR is an indicator that directly measures the anti-tumor activity of drugs and is evaluated in a single-arm test.
The ORR remission criteria should be defined in advance in the protocol before the start of the trial. The evaluation content includes the degree of remission, the duration of remission, and the complete remission rate (without measurable tumor). It does not include stable disease-tumor shrinkage is a direct effect. Stabilization is the natural course of disease.
PFS: Progression-free survival
Defined as: the time from the start of randomization to the progression of tumor (in any aspect) or death (for any reason).
Compared with OS, the node of “deterioration” has been added, and “deterioration” is often earlier than death, so PFS is often shorter than OS, but it can also be evaluated before OS, so the follow-up time is shorter.
The improvement of PFS includes “not worsening” and “not dead”, that is, indirectly and directly reflecting the clinical benefit, which depends on the efficacy/risk of the new treatment and the current treatment.
And because of the addition of the node “deterioration”, different tumor progressions have different definitions, and different studies are prone to bias when judging tumor progression.
Therefore, in the design of clinical trials, the criteria for “tumor progression” must be clearly defined. It also includes methods for assessment, observation, and analysis of PFS. Follow-up and imaging evaluation must be balanced. It is best to have an imaging expert A blind independent adjudication team composed of clinical experts.
PFS includes death, which better reflects the side effects of drugs, and therefore has a better correlation with OS. However, if in the process of evaluating PFS, it is found that most patients died of other diseases instead of tumors, then PFS will inevitably be biased. At this time, I have to say another evaluation indicator similar to PFS-TTP.
TTP: Time to progress
Defined as: the time from the start of randomization to the progression of tumorigenesis (in any aspect).
TTP mainly records disease “deterioration” and does not include “death”. It considers tumor activity. Therefore, when most deaths are not related to tumors, TTP is an acceptable endpoint. In addition, if there are multiple treatments, there is a crossover effect-the difference in TTP will not be masked by the second treatment.
TTP, like PFS, requires a small sample size for evaluation and a shorter follow-up time than OS.
The problem is that if the subject died before worsening, then his TTP must not be observed. At this time, the recorded TTP is incomplete. It is statistically called censoring. This is for missing data. It is difficult to determine the deadline for processing and data.
In addition, since most clinical trials are not double-blind, this introduces bias into TTP decisions. However, the follow-up of patients is difficult: it is necessary to determine the lesions of all parts, the follow-up time and interval are different, there will be differences in TTP, and it is difficult to determine the clinical significance of the difference.
It can be seen that TTP is inferior to PFS in predicting clinical benefits, there are many problems, and it also requires a clear definition and assessment of “progress”.
DFS: Disease-free survival
Defined as: the time from the start of randomization to the recurrence of the disease or death (for any reason).
DFS is most commonly used in the research of adjuvant therapy after radical surgery or radiotherapy. It is currently used as the main approval basis for adjuvant hormone therapy for breast cancer, adjuvant therapy for colon cancer, and adjuvant chemotherapy for breast cancer.
Recurrence of the disease requires careful follow-up, and recording is also difficult, and cancer patients often have comorbidities that can easily interfere with the judgment of DFS.
When the patient died outside the hospital, the progress of the tumor was not recorded in advance. At this time, autopsy is often not possible, and the recurrence cannot be determined.
TTF: Time to treatment failure
It is defined as: from the beginning of randomization to “withdrawal from the trial”, the reasons for withdrawal may be patient rejection, disease progression, patient death, adverse events, etc.
Since it does not only show the efficacy of drugs, it is not recommended for efficacy confirmation tests.
The essence of TTF is an index with comprehensive characteristics. Therefore, it can cause a reduction in toxicity and potentially affect the production of expected curative effects.
~~ What is the difference between OS, PFS and DFS? ~~~
(source:internet, reference only)