# Running CBD and the Ketogenic Diet Together: What a 58-Patient Johns Hopkins Cohort Found

> **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637)
> **Publisher:** CED Clinic (https://cedclinic.com)
> **Canonical URL:** https://cedclinic.com/cbd-and-ketogenic-diet-for-epilepsy-combination-study/
> **Published:** 2026-09-13T10:53:56-04:00 | **Last Modified / Clinically Audited:** 2026-09-28T10:38:53-04:00
> **Clinical Summary:** A multicenter cohort of 58 patients used CBD and ketogenic diet for epilepsy together. Order of introduction mattered, and ketosis mostly held.

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CED Clinical Relevance #71Strong Clinical RelevanceCombining cannabidiol with the ketogenic diet is a question that comes up routinely with families managing drug-resistant epilepsy. Published description of what happens when both are run at once has been limited, which is the gap this cohort addresses.

Two established treatments for drug-resistant epilepsy are frequently used at the same time, and until recently nobody had published much on what that combination looks like in practice. A Johns Hopkins group reviewed 58 patients who received both. The most useful findings are not about efficacy. They are about ketosis, liver enzymes, and the order in which the two therapies were started.

Clinical Insight | CED Clinic

A multicenter retrospective cohort published in *Epilepsy Research* describes 58 children and adults who received cannabidiol and ketogenic diet therapy concurrently. Seizure outcomes resembled what is reported for either therapy used on its own, and the authors position the combination as a reasonable additive option rather than a step change.

The signal the authors flag is one of sequencing: greater seizure reduction was seen when CBD was started before the ketogenic diet rather than after. This was an observed pattern within an uncontrolled cohort, not a randomized comparison.

EpilepsyCannabidiolKetogenic DietPediatric NeurologyClinical Research
AudiencePatients, caregivers, and cliniciansPrimary TopicCombined cannabidiol and ketogenic diet therapy in drug-resistant epilepsySource[Read the full source](https://doi.org/10.1016/j.eplepsyres.2026.107815)
Why This Matters

Roughly one in three people with epilepsy continues to have seizures despite adequate trials of two or more appropriately chosen medications. For that group, cannabidiol and ketogenic diet therapy are two of the few remaining evidence-supported options, and many families end up on both. Whether the two interfere with each other has been an open practical question rather than a theoretical one.

This cohort answers a narrower question than the headline suggests. It does not tell us that the combination outperforms either treatment alone. It tells us what happened, biochemically and clinically, in 58 real patients who were given both, which is information clinicians and families have been working without.

What the Study Actually Did

The paper, *Concurrent use of ketogenic diet therapy and cannabidiol in children and adults with epilepsy: A multicenter retrospective cohort study*, appeared in *Epilepsy Research* on May 5, 2026. The authors are Lauren M. Hinkley, Mackenzie C. Cervenka, Stacey K. Bessone, Zahava Turner, and Eric H. Kossoff, working at the Johns Hopkins University School of Medicine and Johns Hopkins All Children’s Hospital. Kossoff and Turner have spent years running one of the larger ketogenic diet programs in the United States, which is worth knowing when reading their description of how these patients were managed.

The team identified 58 patients treated with cannabidiol and ketogenic diet therapy at the same time between 2018 and 2025. Median age at the start of combination therapy was 2 years, with a range from infancy to 60 years, so this is a heavily pediatric population. Average duration of combined treatment was 17.4 months. Forty-four patients (76 percent) received prescription CBD, meaning Epidiolex, and 14 (24 percent) received artisanal CBD products. Thirty-five (60 percent) were on the classic ketogenic diet rather than a modified variant.

One structural point matters for interpretation and is easy to lose in secondhand coverage. Every patient in this cohort received both treatments. There was no internal CBD-only group and no internal diet-only group. When the authors describe efficacy as similar to either treatment alone, they are comparing against what the published literature reports for monotherapy, not against a control arm they recruited.

Seizure Outcomes, Stated Plainly

At one month of combination therapy, 40 percent of patients had greater than 50 percent seizure reduction. At three months, 28 percent did. Those numbers sit in the same territory as published responder rates for cannabidiol alone and for ketogenic diet therapy alone, which is the basis for the authors’ conclusion that the combination performs comparably rather than synergistically.

The drop from 40 percent to 28 percent between one and three months deserves comment rather than alarm. Attrition of responder rates over time is a familiar pattern in epilepsy cohorts and can reflect tolerance, diet adherence, changes in concurrent medications, or the natural fluctuation of seizure frequency that makes short observation windows unreliable. A retrospective chart review cannot separate those explanations.

The sequencing observation is the part of this paper most likely to influence practice. Thirty-three patients (57 percent) started CBD first and then added the ketogenic diet. Those patients showed greater seizure reduction than patients who went the other way. The authors present this as a reason to consider the combination, particularly when the diet is layered onto established CBD, and they are careful not to call it a causal effect.

The Ketosis Question, Which Is the Practical One

For families already on the ketogenic diet, the first worry about adding CBD is usually whether the carbohydrate content of an oil-based product or the drug itself will break ketosis. This cohort offers reassurance on that point. Eighty-seven percent of patients reported moderate to large urinary ketosis while on both treatments. Among the subgroup who added CBD to an existing ketogenic diet, 8 of 13 had no change in measured ketosis at all.

That is a small subgroup and urinary ketones are a crude measure compared with serum beta-hydroxybutyrate. Still, it is a direct look at what happens to ketosis when CBD is introduced, and it argues against the assumption that the two are biochemically incompatible.

A second practical finding concerns liver enzymes. Among patients who had liver function tests both before and during combination therapy, five (15 percent of those tested) showed increased values, described by the authors as mostly minor. Transaminase elevation is a known effect of cannabidiol, particularly alongside valproate, and this cohort does not suggest the ketogenic diet amplifies it dramatically. It does support checking enzymes rather than assuming they are fine.

Why Two Different Mechanisms Might Be Worth Combining

Cannabidiol and the ketogenic diet reduce seizures through routes that have little overlap. Cannabidiol is a poor direct agonist at CB1 and CB2 and appears to act instead through targets including GPR55 antagonism, modulation of TRPV1 channels, and inhibition of adenosine reuptake. It also raises clobazam levels through CYP interactions, which accounts for part of its observed benefit in some trials.

The ketogenic diet works metabolically. Shifting the brain’s fuel supply toward ketone bodies alters mitochondrial function, reduces glycolytic flux, and appears to shift the balance between glutamatergic and GABAergic signaling. Neither mechanism is a version of the other, which is the pharmacologic rationale for using them together.

Mechanistic independence is an argument for plausibility, not for benefit. Two treatments that act differently can still fail to add anything when combined, and this cohort, with its comparable rather than superior responder rates, is consistent with that possibility. The honest reading is that combining them does not appear to cancel either one out.

What Families and Clinicians Can Do With This

If a patient is stable on cannabidiol and seizures remain inadequately controlled, this paper supports a conversation about adding ketogenic diet therapy rather than treating the two as alternatives. It does not establish that the combination will work, and it does not identify who is likely to respond.

If a patient is already on the diet and CBD is being considered, the ketosis data here are the most directly useful part of the paper. Most patients in this cohort maintained ketosis. That is worth knowing before a family declines CBD out of concern about disrupting a diet that took months to establish.

Ketogenic diet therapy requires supervision by a team that includes a dietitian, and cannabidiol requires attention to drug interactions and liver enzymes. Running both at once compounds the monitoring burden. Nothing in this study changes that, and the median age of 2 years in this cohort is a reminder that most of this experience comes from specialized pediatric epilepsy centers.

Study SnapshotStudy TypeMulticenter retrospective cohort (chart review); observational, no control armInstitutionsJohns Hopkins University School of Medicine; Johns Hopkins All Children’s HospitalParticipants58 children and adults with epilepsy receiving CBD and ketogenic diet therapy concurrentlyAgeMedian 2 years at start of combination therapy (range 0 to 60)Treatment WindowCombination therapy given between 2018 and 2025; average duration 17.4 monthsCBD Source44 patients (76%) prescription CBD (Epidiolex); 14 (24%) artisanal CBDDiet Type35 patients (60%) on the classic ketogenic dietSequencing33 patients (57%) started CBD before starting ketogenic diet therapySeizure OutcomeGreater than 50% seizure reduction in 40% at 1 month and 28% at 3 monthsKetosis and Safety87% reported moderate to large urinary ketosis; 5 of those with paired liver function tests (15%) had increases, mostly minorJournal / PMID / DOIEpilepsy Research 2026;225:107815; PMID 42102520; 10.1016/j.eplepsyres.2026.107815
How Strong Is This Evidence?

This is descriptive evidence from a specialized center, and it should be read as a careful case series rather than a comparative study. Retrospective chart review with no randomization, no control arm, and no blinding cannot establish that either treatment caused the observed seizure changes, let alone that the combination did.

Within that ceiling, the work is solid and useful. The cohort is real, the follow-up averaged well over a year, the biochemical monitoring is documented, and the authors describe their limitations rather than writing around them. For questions about feasibility and tolerability, this is reasonable evidence. For questions about efficacy, it is a starting point for a trial, not a substitute for one.

Where This Paper Deserves Skepticism

The efficacy comparison is indirect. The conclusion that combination therapy performs similarly to either treatment alone rests on comparing this cohort’s responder rates against published monotherapy figures from other populations. Those populations differ in age, syndrome, seizure type, and concurrent medications. Cross-study comparison of responder rates is one of the weaker forms of inference in epilepsy research.

The sequencing finding, which is the most quotable part of the paper, is also the most fragile. Patients whose clinicians started CBD first may differ systematically from those who started the diet first, in seizure severity, in syndrome, in age, or in family resources. With 58 patients split across sequencing groups, the subgroups are small and confounding by indication is likely. The ketosis subgroup of 13 patients is smaller still.

Responder rate at three months was measured in a cohort with an average treatment duration of 17.4 months, so the reported outcomes capture an early window rather than the full course. Urinary ketone measurement is also a coarse proxy for metabolic state.

What This Paper Does Not Show

This study does not show that adding the ketogenic diet to cannabidiol works better than continuing cannabidiol alone. It contains no comparison group that would allow that claim.

It does not identify which patients, syndromes, or seizure types respond to the combination, nor does it establish a CBD dose, a diet ratio, or a titration schedule. It does not demonstrate that starting CBD first causes better outcomes, only that better outcomes were observed in the group that happened to be sequenced that way.

It is not a safety study. Five patients with liver enzyme increases in a cohort of 58, with no systematic adverse event capture, cannot characterize the risk profile of concurrent use.

How This Fits With the Broader Clinical Conversation

Cannabidiol entered mainstream epilepsy care through three randomized programs in Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex, which produced FDA approval of a purified formulation. Ketogenic diet therapy arrived by a different route, with decades of center-based experience and a smaller randomized literature. The two have coexisted in the same clinics for years without a published account of what happens when they are combined.

That gap is characteristic of drug-resistant epilepsy generally. Most patients in this population are on several therapies simultaneously, and almost none of those combinations have been tested as combinations. Descriptive cohorts like this one are how the field usually learns that a pairing is feasible, well before anyone funds a trial to learn whether it helps.

Dr. Caplan’s Take

The result families will care about most is the one about ketosis, not the one about seizures. I have watched parents who spent months getting a child stable on a ketogenic diet refuse to consider cannabidiol because they were told, or assumed, that an oil-based product would undo the work. This cohort suggests that concern is mostly unfounded. Eighty-seven percent stayed in moderate to large ketosis, and most of the small group who added CBD to an existing diet saw no change at all.

The sequencing finding is interesting and I would not build a treatment plan on it yet. In a retrospective cohort, the order in which treatments were started is a decision a clinician made for reasons that are not in the chart, and those reasons tend to track with how sick the patient was. If the effect is real, a prospective study will find it. If it is confounding, a prospective study will find that too.

What I take from this paper clinically is permission to stop treating these two as competing options. They are not. They work through different biology, they appear to coexist without wrecking each other, and for a family that has run out of medications, having two additive tools instead of a choice between them is worth something.

Clinical Bottom Line

Cannabidiol and ketogenic diet therapy can be run concurrently without apparent loss of ketosis in most patients, and liver enzyme changes in this cohort were uncommon and mostly minor. Seizure outcomes looked like what either treatment produces on its own. Treat this as a feasibility and monitoring paper, and monitor liver function when both are in use.

What a Careful Reader Should Take Away

The finding worth carrying into a clinic visit is that concurrent use appears biochemically tolerable and that ketosis generally holds. The finding not to carry forward is any claim that the combination is more effective than either therapy alone, or that starting cannabidiol first causes better seizure control. Neither claim is supported by a cohort of this design.

Evidence Interpretation Guide

Table of Contents

- [How to read an uncontrolled cohort in drug-resistant epilepsy](#How_to_read_an_uncontrolled_cohort_in_drug-resistant_epilepsy)
- [CBD Plus the Ketogenic Diet, Seen From Eight Angles](#CBD_Plus_the_Ketogenic_Diet_Seen_From_Eight_Angles)[Adding CBD is unlikely to break ketosis](#Adding_CBD_is_unlikely_to_break_ketosis)
- [Monitor liver enzymes and do not assume the diet protects](#Monitor_liver_enzymes_and_do_not_assume_the_diet_protects)
- [Comparable to monotherapy is a weak claim](#Comparable_to_monotherapy_is_a_weak_claim)
- [Small subgroups carrying a large conclusion](#Small_subgroups_carrying_a_large_conclusion)
- [Filling a documented gap rather than overturning anything](#Filling_a_documented_gap_rather_than_overturning_anything)
- [Two demanding therapies, one family](#Two_demanding_therapies_one_family)
- [The trial this paper argues for](#The_trial_this_paper_argues_for)
- [Access shapes which version of CBD patients get](#Access_shapes_which_version_of_CBD_patients_get)
- [Frequently Asked Questions](#Frequently_Asked_Questions)[Related](#Related)

## How to read an uncontrolled cohort in drug-resistant epilepsy

The Research QuestionWhat happens clinically and biochemically when cannabidiol and ketogenic diet therapy are used at the same time?The Patient QuestionIf we are already doing one of these, is it safe and sensible to add the other?The Bottom LineCombining the two appears feasible, ketosis mostly holds, and seizure outcomes resemble monotherapy. Whether the combination is better than either alone remains untested.
CED Perspective Lens

## CBD Plus the Ketogenic Diet, Seen From Eight Angles

One retrospective cohort, read through the lenses that matter in epilepsy care.

Lens OverviewFifty-eight patients, median age 2 years, received cannabidiol and ketogenic diet therapy together for an average of 17.4 months. Ketosis was preserved in most, and greater seizure reduction was observed when CBD came first.

#### Adding CBD is unlikely to break ketosis

If your child is on a ketogenic diet that took effort to establish, the main practical question about cannabidiol is whether it will undo that work. In this cohort, 87 percent maintained moderate to large urinary ketosis while on both, and among the small group who added CBD to an existing diet, 8 of 13 saw no change in ketosis.

That is reassurance about compatibility, not a promise of better seizure control. Roughly 40 percent of patients had at least a halving of seizures at one month and 28 percent at three months, which is in line with what either treatment produces by itself.

Lens takeawayCompatibility looks good. Added benefit remains unproven.

#### Monitor liver enzymes and do not assume the diet protects

Cannabidiol is associated with transaminase elevation, particularly in patients on valproate, and this cohort found increases in five of those with paired liver function tests, about 15 percent of those tested. The increases were described as mostly minor, which is consistent with the drug’s known profile and not a reason to avoid the combination.

The clinical action is unchanged by the diet: obtain baseline liver function tests, repeat them after initiation and after dose changes, and review concurrent anticonvulsants for interactions, clobazam in particular.

Lens takeawayBaseline and follow-up liver function testing remains the standard, diet or not.

#### Comparable to monotherapy is a weak claim

The paper’s efficacy conclusion compares this cohort’s responder rates with figures published for cannabidiol alone and ketogenic diet alone in other populations. Those populations were not matched on age, syndrome, or background medications. Comparing responder rates across studies is closer to a rough sanity check than to evidence of equivalence.

Without a control arm, an observed 40 percent responder rate at one month also cannot be separated from regression to the mean, which is a well-documented problem in epilepsy cohorts where treatment changes tend to follow periods of unusually high seizure frequency.

Lens takeawayNo control arm means no efficacy claim, in either direction.

#### Small subgroups carrying a large conclusion

The two findings receiving the most attention rest on the smallest numbers in the paper. The sequencing comparison splits 58 patients into two groups whose treatment order was chosen by clinicians for unrecorded reasons. The ketosis stability finding rests on 13 patients.

Confounding by indication is the obvious concern. Clinicians tend to start the ketogenic diet earlier in patients with particular syndromes and metabolic indications, and later in patients who have already failed other options. That difference alone could produce the observed sequencing pattern.

Lens takeawayCite the sequencing result as a hypothesis, not as guidance.

#### Filling a documented gap rather than overturning anything

Both treatments have independent evidence bases. Purified cannabidiol reached FDA approval through randomized programs in Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex. Ketogenic diet therapy carries decades of center experience and a smaller randomized literature.

What has been thin is published description of the two used together, despite the pairing being common in practice. The authors note that research characterizing interactions between these treatments has been limited. This cohort adds description, not a correction of prior work.

Lens takeawayThe contribution is documentation of a common practice, not a new finding about either therapy.

#### Two demanding therapies, one family

Ketogenic diet therapy requires a dietitian, careful food weighing, micronutrient supplementation, and monitoring for growth, lipids, and kidney stones. Cannabidiol requires dose titration, liver enzyme checks, and attention to interactions. Running both compounds the workload on caregivers rather than splitting it.

Prescription cannabidiol accounted for 76 percent of this cohort, which matters because artisanal products carry variable cannabinoid content and, in some cases, carbohydrate-containing carriers or flavorings that can affect a strict diet. Verified product content is not a minor detail here.

Lens takeawayVerified CBD content and a dietitian on the team are prerequisites, not refinements.

#### The trial this paper argues for

The useful next study is prospective, randomizes order of introduction in patients who are candidates for both, and measures serum beta-hydroxybutyrate rather than urinary ketones alongside seizure diaries and liver enzymes.

A design of that kind would settle whether the sequencing signal is real and would produce the dosing and diet ratio guidance that this cohort cannot provide. Given how often the combination is already used, the question is more about funding priorities than about feasibility.

Lens takeawayRandomize the sequence, measure serum ketones, and the open question closes.

#### Access shapes which version of CBD patients get

Three quarters of this cohort received prescription cannabidiol. Outside of a specialized epilepsy center with insurance navigation support, that ratio often reverses, and families end up with artisanal products of uncertain content.

In April 2026 the DEA moved marijuana contained in FDA-approved drug products and marijuana subject to a state medical marijuana license to Schedule III, while other forms of marijuana remained in Schedule I. That change alters the federal regulatory picture without addressing the coverage and cost barriers that determine whether a family gets a standardized product.

Lens takeawayScheduling reform does not by itself put verified-content CBD in a family’s hands.
Related Reading at CED ClinicContinue exploring the evidence[Cannabinoids in Pediatric Medicine: Evidence-Based Care and Clinical Trials](https://cedclinic.com/cannabinoids-in-pediatric-medicine-evidence-based-care-and-clinical-trials/)

The wider pediatric evidence base that this epilepsy cohort sits inside, including where trial data are strong and where they are thin.

[Read the pediatric review](https://cedclinic.com/cannabinoids-in-pediatric-medicine-evidence-based-care-and-clinical-trials/)[Randomized Trial of a Low-THC Full-Spectrum Cannabis Extract in Epilepsy](https://cedclinic.com/low-thc-full-spectrum-cannabis-extract-epilepsy-trial/)

A controlled trial for comparison, showing what randomization adds to the kind of question this cohort could only describe.

[See the trial data](https://cedclinic.com/low-thc-full-spectrum-cannabis-extract-epilepsy-trial/)[Fenfluramine for Dravet Syndrome: A Stratified Pooled Analysis](https://cedclinic.com/fenfluramine-dravet-syndrome-stratified-analysis/)

Another add-on therapy in the same population, useful for calibrating what a meaningful responder rate looks like.

[Compare the evidence](https://cedclinic.com/fenfluramine-dravet-syndrome-stratified-analysis/)

Join the Conversation

Have a question about how this applies to your situation? [Ask Dr. Caplan](https://benjamincaplan.com/ask-dr-caplan)

Want to discuss this topic with other patients and caregivers? [Join the forum discussion](https://cedclinic.com/interact/discussion-forums/forum/cannabis-industry/)

## Frequently Asked Questions

Can you take CBD and follow a ketogenic diet at the same time?

Yes. A 2026 multicenter cohort of 58 patients describes what that looks like in practice, filling a gap the authors note has had only limited research. Eighty-seven percent of patients maintained moderate to large urinary ketosis while receiving both cannabidiol and ketogenic diet therapy. Among the smaller group who added CBD to an existing diet, 8 of 13 showed no change in ketosis. Both therapies still require supervision, and liver function should be monitored.

Does CBD oil break ketosis?

In this cohort it generally did not. Most patients on combined cannabidiol and ketogenic diet therapy remained in moderate to large urinary ketosis, and the majority of those who added CBD to an established diet showed no measurable change. The caveats are that urinary ketones are a rough measure compared with serum beta-hydroxybutyrate, and that carbohydrate-containing carriers or flavorings in some artisanal products could behave differently than the prescription formulation most patients received.

Did combining CBD and the ketogenic diet reduce seizures more than either alone?

The study cannot answer that. Every patient received both treatments, so there was no internal comparison group on one therapy alone. Greater than 50 percent seizure reduction occurred in 40 percent of patients at one month and 28 percent at three months, figures the authors describe as comparable to published results for either therapy by itself. Whether the combination adds benefit requires a controlled trial that has not been run.

Does the order of starting CBD and the ketogenic diet matter?

The authors observed greater seizure reduction in patients who started cannabidiol before adding ketogenic diet therapy, and 57 percent of the cohort was sequenced that way. This is an observation from an uncontrolled chart review, not a randomized comparison. Clinicians chose the order for reasons not captured in the records, and those reasons may track with how severe the epilepsy was. Treat the finding as a hypothesis worth testing.

Who was in this study?

Fifty-eight children and adults treated at Johns Hopkins University School of Medicine and Johns Hopkins All Children’s Hospital between 2018 and 2025. The median age at the start of combination therapy was 2 years, with a range from infancy to 60 years, so the population is predominantly pediatric. Average duration of combined treatment was 17.4 months. Forty-four received prescription cannabidiol and 14 received artisanal CBD products.

Does adding CBD to a ketogenic diet raise liver enzyme risk?

Among patients in this cohort who had liver function tests before and during combination therapy, five showed increased values, about 15 percent of those tested, and the authors described the increases as mostly minor. Transaminase elevation is a recognized effect of cannabidiol, particularly alongside valproate. Nothing here suggests the ketogenic diet worsens that risk, but it reinforces the case for baseline and follow-up testing.

How do CBD and the ketogenic diet work differently?

Cannabidiol is a weak direct agonist at CB1 and CB2 and appears to act through other targets, including GPR55 antagonism, TRPV1 channel modulation, and adenosine reuptake inhibition, and it raises clobazam levels through liver enzyme interactions. The ketogenic diet works metabolically, shifting brain fuel toward ketone bodies, altering mitochondrial function, and changing the balance of excitatory and inhibitory signaling. The mechanisms do not overlap, which is the rationale for combining them.

Should a family ask about adding the ketogenic diet if CBD is not working well enough?

It is a reasonable conversation to have with a neurologist, and this study supports treating the two as additive options rather than alternatives. It does not predict who will respond. Ketogenic diet therapy requires a dietitian and ongoing monitoring for growth, lipids, and kidney stones, so the decision depends on the family’s capacity to sustain it as much as on the seizure picture.

 

### Related

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### Verification & Medical Governance

- **Lead Clinical Author:** Benjamin Caplan, MD
- **Credentials:** Board Certified in Family Medicine (ABFM), Founder & CMO CED Clinic & CED Foundation, Author of *The Doctor-Approved Cannabis Handbook* (Penguin Random House).
- **Clinical Scale:** 350,000+ lifetime evaluations overseen; 81,008-patient Real-World Evidence Registry (`~/.ced_rwe_vault.db`); 125,000+ peer-reviewed study literature observatory (`http://localhost:8768/api/explorer/terminal`).
- **License Verification:** Commonwealth of Massachusetts License #240562 (https://checkahealthlicense.mass.gov/).
- **NPI Registry:** 1962722637 (https://npiregistry.cms.hhs.gov/provider-view/1962722637).
- **Ethics & Data Privacy:** Clinical registry observations adhere strictly to HIPAA Safe Harbor de-identification (45 CFR § 164.514(b)) and criteria for secondary research exemption under 45 CFR § 46.104(d)(4).