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Unmasking bias in your survival analysis

Competing risks methods are advanced statistical approaches designed to analyze multiple events that may simultaneously impact a patient, using methods such as cumulative incidence functions and Fine & Gray models. These methods are essential in survival analysis, particularly in situations where multiple risks can interact and interfere with another, making traditional survival analyses potentially biased or incomplete.

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Competing risks methods are advanced statistical approaches designed to analyze multiple events that may simultaneously impact a patient, using methods such as cumulative incidence functions and Fine & Gray models. These methods are essential in survival analysis, particularly in situations where multiple risks can interact and interfere with another, making traditional survival analyses potentially biased or incomplete.

Survival analysis 

Survival analysis encompasses a wide range of statistical methods designed to handle censored data. Censoring occurs when we can only partially observe the timing of an event – we know that a subject hasn’t experienced the event (such as death, system failure, or disease recurrence) up until a certain date, but we lose track of them after that point. These analyses allow for the inclusion of incomplete information in the analysis, enabling researchers to estimate survival probabilities and time-to-event outcomes more accurately.

What is a competing risk?

A competing risk is an event that can occur in place of the event of interest, thereby preventing its occurrence or accurate observation. For instance, if a patient dies prior to being hospitalized, the hospitalization event is no longer observable.

Applications of competing risk analyses

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Treatment discontinuation

Treatment discontinuation is a classic competing risks scenario, as patients may stop treatment for various reasons: experiencing adverse effects, failing to adhere to the treatment i.e. non-adherence, dying before treatment completion, or achieving their therapeutic goals (e.g. clinical remission or desired treatment outcome).

 

❓Research questions
  • What is the rate of treatment discontinuation due to death or treatment switch?
  • What is the impact of patient characteristics on treatment discontinuation ?
🔍 Event of interest
  • Treatment switch
⚠️ Competing event
  • Treatment discontinuation for others reasons (death, adverse event)

Clinical events

A specific type of competing risk scenario, known as a semi-competing risk situation, arises when the occurrence of death precludes the occurrence of the clinical event of interest, while the reverse is not true. The clinical event of interest could involve the occurrence of adverse events, disease progression, or treatment failure.

 

❓Research questions
  • What is the rate of rehospitalizations following initial surgery?
  • What is the impact of the surgical method on rehospitalization rates?
🔍 Event of interest
  • Rehospitalization
⚠️ Competing event
  • Death prior to rehospitalization

    Tableau à styliser

    Données primaires SNDS
    image ici Représentativité Échantillon Exhaustivité
    image ici Caractéristiques
    socio-démographiques des patients
    Sur mesure Âge, sexe, lieu de naissance, lieu de résidence, statut vital

    Insertion de vidéo youtube

    Critère Données primaires SNDS
    Icon Représentativité Données primaires Échantillon SNDS Exhaustivité
    Icon Caractéristiques socio-démographiques des patients Données primaires Sur mesure : Âge, sexe, lieu de naissance, lieu de résidence, statut vital SNDS Âge, sexe, lieu de naissance, lieu de résidence, statut vital
    Icon Description de la maladie Données primaires Diagnostic et histoire de la maladie, évaluation clinique (stade / sévérité) SNDS Diagnostic et histoire de la maladie (proxy)
    Icon Parcours de prise en charge Données primaires Description des traitements et du parcours de prise en charge
    Motifs d'arrêt de traitement, tolérance / sécurité
    SNDS Traitements remboursés, parcours thérapeutiques
    Icon Paramètres biologiques et cliniques Données primaires Résultats examens biologiques radiologiques / investigations cliniques SNDS -
    Icon Qualité de vie Données primaires PROMs / PREMs SNDS -
    Icon Coûts Données primaires Recueil fastidieux et compliqué avec une qualité discutable SNDS
    Icon Période d'étude - suivi Données primaires Suivi à court et long terme, mais étude coûteuse SNDS Suivi long terme (morbidité, efficacité, statut vital)
    Critère ✓ Utilisation du NIR ✗ Pas d'utilisation du NIR
    Appariement direct Méthodologie d'appariement ✓ Utilisation du NIR Appariement direct
    (Appariement reposant sur le numéro d’identification anonyme du patient : nécessite son recueil dans la base à apparier, date de naissance et sexe)
    ✗ Pas d'utilisation du NIR Appariement indirect
    (Appariement reposant sur des variables communes aux deux bases et suffisamment discriminantes : date de naissance, sexe, dates de soins…)
    CNIL Autorisation réglementaire ✓ Utilisation du NIR Autorisation CNIL ✗ Pas d'utilisation du NIR Méthodologie de référence
    Qualité Qualité de l'appariement ✓ Utilisation du NIR Excellent
    (proche de 100%)
    ✗ Pas d'utilisation du NIR Variable selon la qualité et la typologie de la base
    Responsable Responsable d'appariement ✓ Utilisation du NIR Appariement réalisable par la CNAM ✗ Pas d'utilisation du NIR Appariement réalisable par le bureau d'étude
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    Accès à l’application
    App Store App Store
    Public
    Inhouse Inhouse
    Privé
    Custom Apps Custom Apps
    Privé
    Validation de l’application
    App Store App Store
    Apple
    Inhouse Inhouse
    L’entreprise
    Custom Apps Custom Apps
    Apple
    Plateforme de distribution
    et mise à jour
    App Store App Store
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    Inhouse Inhouse
    Propre à l’entreprise
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    App Store
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    Conclusion

    In conclusion, understanding and accurately modeling competing risks is fundemental to conducting valid survival analyses and for obtaining reliable and meaningful results. Whether in clinical trials, epidemiological studies, or medical research, failure to account for events that may interfere with the occurrence of the primary outcome of interest can significantly impact their interpretation. Understanding the interplay between competing events not only ensures statistical rigor but also provides clinicians with more reliable evidence for patient care.

     

    References

    Ignoring competing event in survival analyses: the amplitude of the bias in Kaplan-Meier estimates

    Competing risks in SNDS: application to amputation risk in acute ischemia

    Ignoring competing event in survival analyses: the amplitude of the bias in Kaplan-Meier estimates