Scientific Safety Research

Scientific Safety Research Services include comparison of blinded adverse event rates with background rates and close scrutiny of serious adverse events for causality during the clinical trial phase. Post-marketing Safety Research Services include analysis of aggregate unlabeled adverse events for a causal association, mitigation of labeled events by evaluating causal role of underlying disease, assessing impact of microbial contamination of non-sterile oral formulations and authoring of drug safety reports.

RxMD's niche in drug safety research is in both blinded assessment of safety during the clinical trial phase and medical assessment of safety signals (from proportional reporting, literature and regulatory requests) in the post-marketing phase.

Blinded Signal Detection

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

Medical Review of Unlabeled Adverse Events

RxMD requested to review rare AE in client'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 label updated to reflect association. RxMD awarded preferred vendor for future signal evaluation.

Establishing Causal Role of Underlying Disease

Sponsor required to change label for a billion dollar drug (to reflect new 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.

Evaluation of Microbial Contamination

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.

NDA Safety Review

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 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.

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.

Safety Review

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.

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.

Pregnancy review

RxMDs exhaustive review of maternal outcomes (Live birth, Spontaneous abortion, therapeutic abortion, stillbirth, pregnancy ongoing, unknown/not reported) and foetal outcomes (Normal [normal delivery or normal foetus] or abnormal [birth defect, low birth weight, small for gestational age, intra-uterine growth retardation, etc.]) 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 (e.g. malformation [poor tissue formation], deformation [unusual forces on normal tissue], disruption [breakdown of normal tissue] or dysplasia [abnormal cell organization in tissue]) and the trimester 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.