---
title: >-
  Negative Control Outcomes to Assess the Comparability of Biologics versus
  Small-molecule Therapeutics for Osteoporosis: Considerations for Differential
  Non-adherence
description: >-
  Explore this publication on real-world evidence: Negative Control Outcomes to
  Assess the Comparability of Biologics versus Small-molecule Therapeutics for…
date: '2022-01-01'
author: M. Alan Brookhart, PhD, Lydia Feinstein, Peter S. Samai
category: Publications
tags:
  - ICPE
  - Care
  - 'Yes'
  - Oral Presentation
  - Methods/Pharmacoepi
  - R&D
canonical_url: >-
  https://www.headwaterscience.com/resources/publications/icpe/negative-control-outcomes-to-assess-the-comparability-of/
source: Headwater Science
license: © 2026 Headwater Science. All rights reserved.
slug: negative-control-outcomes-to-assess-the-comparability-of
id: 4GM4iU2i7rjK4LnY9GHRRB
contentType: article
---

## Challenge

NCOs had been applied primarily in studies of conventional small-molecule drugs, but whether they could reliably assess the comparability of biologic versus small-molecule treatment groups had not been evaluated in an osteoporosis setting.

## Solution

Target RWE researchers applied NCOs to compare biologic versus small-molecule treatment groups in an osteoporosis cohort, demonstrating how NCO balance or imbalance reveals whether standard confounding adjustment has achieved comparable groups.

## Impact

Demonstrating NCO utility for biologic vs. small-molecule comparisons validates the approach for an expanding range of comparative effectiveness questions relevant to pharma partners developing biologics.

## Use Cases / Links

NCO-based comparability assessment for biologic vs. small-molecule comparative effectiveness in pharma programs, NCO gating framework extension to biologic therapy comparative effectiveness design