Drugs' Other Side-Effects

• Author: Craig J. Konnoth
• Position: Associate Professor of Law, University of Colorado School of Law
• Pages: 171-237

171

Drugs’ Other Side-Effects

Craig J. Konnoth*

ABSTRACT: Drugs often induce unintended, adverse physiological reactions

in those that take them—what we commonly refer to as “side-effects.”

However, drugs can produce other, broader, unintended, even non-

physiological harms. For example, some argue that taking Truvada, a drug

that prevents HIV transmission, increases promiscuity and decreases condom

use. Expensive Hepatitis C treatments threaten to bankrupt state Medicaid

programs. BiDil, which purported to treat heart conditions for self-identified

African-Americans, has been criticized for reifying racial categories. Although

the Food & Drug Administration (“FDA”) has broad discretion under the

Food, Drugs, and Cosmetics Act (“FDCA”) to regulate drugs, it generally

considers only traditional side-effects. Neither the agency, courts, nor scholars

have offered a systematic account of how to regulate collateral effects that do

not involve direct physiological harm to the drug’s recipient.

This Article more clearly defines these harms and explains why and how the

FDA should take them into account. It starts by offering three characteristics

that distinguish these harms from those the FDA traditionally considers. First,

unlike traditional harms, these harms are often the indirect rather than direct

result of drug consumption. Second, they often affect third parties rather than

the person that ingests the drug. Third, they might often raise non-health

considerations, such as economic or moral concerns.

Both ethically and legally, the FDA should take into account such indirect,

third-party, and non-health harms to some degree at least. Bioethical

considerations, administrative accountability and practice, as well as

pragmatic policy interests, all counsel considering these harms. But how

should the FDA do so? As the Article explains, the FDCA offers a variety of

choices for FDA intervention, ranging in intensity from flat approval refusals

to mandating labeling or prescription guidelines. In most cases, various

considerations suggest that more limited forms of intervention are usually

appropriate to address these harms.

*

Associate Professor of Law, University of Colorado School of Law. My thanks to Patti

Zettler, Hank Greeley, Lewis Grossman, and Pierre Schlag for helpful conversations and detailed

comments. My thanks also to participants of the Colorado Law Works in Progress Workshop, the

Stanford Law Biolawpalooza, the Health Law Professors Conference, the Mid-Atlantic Health Law

Conference, and the Duke Culp Colloquium.

172 IOWA LAW REVIEW [Vol. 105:171

I.INTRODUCTION ............................................................................. 173

II.DESCRIBING THE PROBLEM ........................................................... 178

A.THE FDA OVERSIGHT PROCESS ................................................ 178

B.CABINING THE QUESTION ........................................................ 181

III.DRUG WARS .................................................................................. 183

A.INDIRECT HARMS .................................................................... 183

B.THIRD-PARTY EFFECTS ............................................................ 186

C.NON-HEALTH EFFECTS ............................................................ 189

D.SHORTCOMINGS ...................................................................... 193

1.Lack of Collection of Data or Assessment of

Concerns ........................................................................ 193

2.Failure of Process to Incorporate Data into

Concerns ........................................................................ 195

3.Lack of Systematization Across Drugs .......................... 195

IV.THE ETHICAL CASE FOR CONSIDERING ‘OTHER’ SIDE-EFFECTS ... 196

A.INDIRECT HARMS .................................................................... 196

B.THIRD-PARTY EFFECTS ............................................................ 199

C.NON-HEALTH EFFECTS ............................................................ 202

V.THE POLICY CASE FOR CONSIDERING ‘OTHER’ SIDE-EFFECTS ...... 207

A.CONSEQUENTIALISM ................................................................ 207

B.ACCOUNTABILITY AND LEGITIMACY ......................................... 211

C.INFORMATION ......................................................................... 215

D.OBJECTIONS ............................................................................ 216

1.Time and Cost ............................................................... 216

2.The Kitchen Sink/Overreach Objection ..................... 218

3.Expertise ........................................................................ 219

4.Federalism...................................................................... 221

VI.REGULATOR Y CALIBRATION .......................................................... 223

A.DESCRIBING REGULATORY CALIBRATION .................................. 223

B.JUSTIFYING CALIBRATION ......................................................... 226

C.STATUTORY CALIBRATION ....................................................... 230

1.Approval ......................................................................... 231

2.Advertising/Labeling Review ....................................... 233

3.Post Approval/Marketing Power .................................. 234

4.Adjusting the Process .................................................... 234

VII. CONCLUSION ................................................................................ 235

2019] DRUGS’ OTHER SIDE-EFFECTS 173

I. INTRODUCTION

Drugs produce side-effects—that is, unintended, incidental,

consequences of ingesting the drug.1 Benadryl causes drowsiness;2 Zoloft

causes nausea;3 Warfarin might result in internal bleeding.4 Sometimes such

side-effects are serious enough for the Food & Drug Administration (“FDA”)

to deny approval of the drug.5 And the public hears of the side-effects of some

drugs only after they are approved, marketed, and even prescribed.

Sometimes these side-effects are positive. NyQuil is frequently used as a

sleep medication because it produces drowsiness.6 Manufacturers might even

market these desirable side-effects.7 But most of the time, side-effects are

negative, causing discomfort, danger, and even death. These side-effects have

in common one important feature: they all involve physiological reactions to

the chemical effects of the drug. Government agencies have been equipped

to deal with these physiological effects—their experts can identify side-effects

through the pre-approval clinical trials and post-approval drug surveillance,

and their legal powers permit them to withhold or withdraw approval of drugs

that have dangerous effects.8

1. Many of my concerns apply to food and devices as well. However, the cultural role that

food plays renders distinguishing between main and side-effects impossible. The regulation of

devices differs slightly from that of drugs—enough that clarity counsels focusing only on drugs

for the purpose of this Article.

2. Diphenhydramine Hydrochloride-Drug Summary, PDR, https://www.pdr.net/drug-summary/

Diphenhydramine-Hydrochloride-diphenhydramine-hydrochloride-1140.941 [https://perma.cc/

H36P-FKQ4]. Benadryl is a brand name of diphenhydramine hydrochloride.

3. Sertraline Hydrochloride-Drug Summary, PDR, http://www.pdr.net/drug-summary/Zoloft-

sertraline-hydrochloride-474.3608 [https://perma.cc/HA6S-8FHS]. Zoloft is the brand name of

sertraline hydrochloride.

4. Charles Ornstein, Popular Blood Thinner Causing Deaths, Injuries at Nursing Homes,

PROPUBLICA (July 12, 2015, 7:00 PM), https://www.propublica.org/article/popular-blood-

thinner-causing-deaths-injuries-at-nursing-homes [https://perma.cc/3KKJ-HBUX] (“Coumadin

(or warfarin) is a medicine often prescribed to older adults for prevention of strokes, blood clots

and heart attacks. However, the dose must be closely monitored. Too much can lead to internal

bleeding.”).

5. See W. Kip Viscusi & Richard J. Zeckhauser, Reg ulating Ambiguous Risks: The Less than

Rational Regulation of Pharmaceuticals, 44 J. LEGAL STUD. S387, S388–89 (2015).

6. Christine Skopec, The Most Dangerous Over-the-Counter Cold Medications, SHOWBIZ

CHEATSHEET (Dec. 5, 2017), https://www.cheatsheet.com/health-fitness/dangerous-over-the-

counter-cold-medications.html [https://perma.cc/MDR6-GHJN]; David Warren, Does Nyquil

Help You Sleep? What You Need to Know [Experts Say], WFM HEALTH, https://wealthformy

health.com/does-nyquil-help-you-sleep [https://perma.cc/J7Q9-D68X]. Though it is often

marketed as such.

7. United States Calming and Sleepi ng Market: New Insights, COMPANIES & MKTS. (June 9, 2015,

10:12 PM), https://advance.lexis.com/document/index?crid=23a32442-d5c1-42d0-a59a-bbfbc5eb

fb0b&pdpermalink=c043930e-1f86-45bb-94c1-e678af38d170&pdmfid=1000516&pdisurlapi=true. It

is notable that off-label marketing is impermissible in FDA’s view. While labels indicat e adverse

effects, indicating that those are benefits might be construed as misleading in the FDA’s view.

8. See infra Part V.