Characteristic | Goal of Randomized Clinical Trial (RCT) | Real World Data (RWD) (Possible confounders noted) |
---|---|---|
Treatment assignment | Randomization | Agreement to treat between patient and physician (Ideal might be limited due to insurance coverage or other considerations) |
Concomitant medications | Specified in protocol | Some patients may be receiving concomitant medications excluded in the RCT protocol. Underreporting of concomitant medications more likely than in RCT |
Risk/benefit | Data monitoring committees and cardiac panels scrutinize adverse events and can request further information on adverse-event experiences | Limited to the data in the database or individual event reporting. Insurance data may not include deaths as they are not a billable event |
Adverse event reporting | Attempts are made to be complete Events reported in structured format and actively collected as part of the ongoing clinical assessment | Reporting may be less rigid and may be over- or under-inclusive. Diagnosis often not verified, and a tendency not to report well established toxicities may also exist. History may be incomplete |
Attribution of a cardiotoxic event to drug of interest | Not always possible to separate drug-induced change from a confounding factor | Not always possible to separate drug-induced change from a confounding factor. Inconsistent reporting of events may compromise the validity of conclusions |
Medication and other compliance | Often recorded as per the protocol. Deviations in compliance exist.17 | Data on drug compliance may not be sought |
Clinical endpoints | Pre-specified efficacy and cardiac events adjudicated according to schedule in most trials | Adverse event noted clinically, and conditions of concern may be scrutinized. Endpoint data often not obtained |
Confounders | Balance between measured and unmeasured confounders may be handled by randomization | Many unmeasured confounders allow for a more comprehensive overview of adverse events |
Inclusion/Exclusion Criteria | Precisely defined in protocol | Patients may have comorbidities or take concomitant medications that are not allowed in the RCT and are not reported in database |
Baseline variables | Attempts made to limit variables by inclusion and exclusion criteria | Often baseline variables not adequately measured |
Cardiovascular data | Consistently measured using standardized techniques at defined intervals | Technique and timing may vary |