Drug Safety

RxMD’s Safety (Science) services distinguish it from other Safety (Operations) service providers. There is constant application of strategic thought before execution. Be it the study phase or post-approval, we provide a wide spectrum of services from pre-marketing risk and causality assessment to blinded review of safety and pharmacovigilance.

Establishing Causal Role of Underlying Disease

Sponsor required to change label for a billion-dollar drug (to reflect new adverse events [AEs]) and given one year to present follow up data. RxMD joins Sponsor’s core team to review, summarize and categorize AEs from safety database and compare with market research data on natural history of disease being treated. At FDA advisory meeting, team demonstrates that AEs occur with disease irrespective of drug. FDA consents to change label again to reflect that AEs could also be disease related. A likely first for the Regulator to acknowledge role of disease in AE after initially ascribing AE to drug.

Sponsor conducting large Phase II global clinical trial. RxMD requested to conduct a blinded assessment of safety on an ongoing basis to detect signals. RxMD detects a higher overall adverse event rate for cutaneous reactions in treatment arms compared to background rate. On unblinding, findings are confirmed, and development of the drug is halted.

Blinded Signal Detection

Medical Review of Unlabeled Adverse Events

RxMD requested to conduct post-marketing signal detection and review rare adverse event in Sponsor’s drug safety database. RxMD identifies possible association and recommends label change. Suggestion meets with stiff resistance from Sponsor. RxMD’s assessment supported by Sponsor’s internationally renowned experts. Company Core Data Sheet and label updated to reflect association. RxMD awarded preferred vendor for future signal evaluation.

Three months prior to FDA advisory for NDA, US-based Sponsor, anxious about safety data, enlists RxMD to review safety data. Sponsor uploads patient level safety data from clinical trials and safety database onto RxMD’s ftp server located in India. RxMD reviews 362 cases, identifies 16 cases of critical significance (missing or incorrect Serious Adverse Events [AEs]) and 55 of moderate significance (possibly missing or incorrect Serious AEs). RxMD collaborates with Sponsor to proactively address issues and drug ultimately meets with FDA approval.

NDA Safety Review

Class Action Lawsuit

Following an adverse effect and regulatory assessment report, Sponsor requests RxMD to extensively evaluate causality and prepare a safety brief for a class action lawsuit. RxMD defines a reproducible methodology for identification and systematic manual medical review of several thousands of cases from Sponsor’s drug safety database, develops strategy for review of claims databases, liaises with Sponsor’s external subject-matter experts and finalizes report to be submitted to regulators and the defense team.

RxMD contracted to write Integrated Summary of Safety. RxMD detects high incidence of accidental injuries presumed by Sponsor as unlikely to be drug related. RxMD requests Sponsor to gather additional information on associated events (ataxia, dizziness, vision defects) to categorize accidents for analysis. RxMD concludes accidents are unrelated to drug, which subsequently meets FDA approval.

Integrated Summary of Safety

Pregnancy Review

RxMD’s exhaustive review of maternal and fetal outcomes established that a commonly prescribed antiviral had no demonstrable toxicity with use in pregnancy. The evaluation for association with birth defects took into consideration any birth defect, its mechanism and the time of exposure (early or late) to establish if a causal association was even possible. RxMD has since evaluated pregnancy reporting for more than 40 drugs. Two of the pregnancy reports that established lack of demonstrable toxicity of the commonly prescribed antiviral have been published. The initial publication is available here and the follow-on publication (with a larger dataset) is available here.

Sponsor’s multi-million dollar drug inventory unreleased due to microbiologic contamination. RxMD authors a medical assessment evaluating the contaminant, degree of contamination, and sets company-wide standards for the evaluation of suspected microbial contamination. RxMD awarded preferred vendor for evaluation of all microbial contaminations.

Evaluation of Microbial Contamination

PSUR Creation

Following EMEA strictures on quality of first PSUR (for drug with sales over billion dollars), Sponsor approaches RxMD few days prior to data lock for second PSUR. RxMD detects several discrepancies in assigning expectedness, inconsistent coding of terms, and inadequate quality of programmed outputs. RxMD manually generates and QCs tables from Sponsor’s outputs to populate approximately 40 tables to finalize PSUR within critical timelines.

FDA audit finds significant gaps in safety reporting from non-interventional programs and non-interventional studies. RxMD tasked with review of approximately 10,000 events to identify safety signals. RxMD establishes process for programmatic review and completes review well within time.

Safety Review

Post-marketing Safety (in response to a public health crisis)

Sponsor under intense pressure to provide an overall safety statement of drug to be used in a public health crisis. RxMD authors report summarizing and confirming overall safety of Sponsor drug. Report submitted to health authorities and subsequently published. Abbreviated report available as a publication here.

Sponsor’s drug withdrawn from major markets because of unanticipated toxicity. Sponsor identifies pharmacogenomic marker for adverse event and submits Risk Management Plan (RMP) to EU authorities who request extensive revision of RMP. RxMD reviews several hundred listings, figures and tables from pharmacogenomic study, previous study reports and rewrites RMP to tell convincing story in a free standing, independent document. Document is well received by the Sponsor, who submits revised RMP and returns to RxMD for other projects.

Dx Rescue for Rx

Client Speak

Austin Gromatzky

RxMD provides outstanding service to us. They’re fast, reliable, and extremely capable. I wholeheartedly recommend their services to any pharmaceutical company requiring

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Robert Pordy, MD

I am very pleased to recommend the services of RxMD. They provided us a resource in Vis Niranjan, a consummate pharmaceutical physician – bright, knowledgeable and diligent.