Compassionate access policies
in the U.S. are fraying the ties between patients, and the drug companies,
physicians and regulators that are essential for medical progress.
Now that the Josh Hardy case
has let the social media genie out of the bottle, it is urgent that these
groups, as well as lawmakers, work together to quickly create a system that is
seen by the public as a fair way to adjudicate complex interests that can be
both in conflict and legitimate (see Cover Story).
The result needs to be a
process that is transparent so all the stakeholders understand the rules and
the criteria for granting or denying access, and it must be applied in a way
that the stakeholders can see the criteria have been applied objectively and
with due diligence.
BioCentury has identified some
basic principles that should guide responses to compassionate use requests no
matter who does the answering (see "Decision Tree for Compassionate
Two broad ideas are at their
core. First, access should be granted to as many patients who are out of
options and could benefit as possible, even if access cannot be provided to all
Second, when there are
impediments to providing compassionate access, all the
stakeholders have a responsibility to try to lift them.
The key to implementing these
principles in a way that will make the outcome of tough decisions more
equitable, easier to understand and therefore more acceptable, is the creation
of an independent third party that can make recommendations based on a
dispassionate assessment of the facts.
It also would be desirable to
create sources of funding for compassionate access that can be used when
provision of treatment is beyond the manufacturer's means. Compassionate access
is in the public interest, so the public should help pay for it.
The principles guiding
decisions about compassionate access requests are the same regardless of
differences among individual requests.
The starting point is the
principle that compassionate access to experimental therapies should be
restricted to patients with life-threatening or serious illnesses who have no
A clinical trial is an
acceptable alternative. Compassionate access should not be a ticket to avoid
the risk of being randomized to standard of care or even placebo. Doing so
would make it difficult, and in some cases impossible, to enroll patients in
trials that are essential to determining safety and efficacy.
Patients who are eligible for a
clinical trial therefore should not be granted early access, but rather should
be given information about enrolling in appropriate trials.
The next question is whether
granting early access could substantially slow or prevent FDA approval,
which would mean slowing or denying access to the broader patient population.
In the case of Josh Hardy, FDA and Chimerix
Inc. were able to create a pilot trial of the company's brincidofovir
in a new indication, which enabled the medicine to reach the boy and create a
pathway to a registration study in the second setting (see "The Josh
Hardy Chronicles," A7).
But if risks to timely approval
truly cannot be mitigated, compassionate access should not be granted. It is
difficult to deny patients access to hope, but this must be done if providing
an experimental treatment would imperil access by much larger numbers of future
The next question is whether
there is adequate supply of the experimental medicine to provide access to all
If supply is too constrained to
meet demand, funds should be provided to increase supply if it is possible to
do so. This could include a dedicated fund to pay for expanding production.
If supply cannot be increased
even with the provision of additional money, capacity and personnel, but there
is enough supply to help some patients, then an equitable access program should
necessarily mean equal, nor must access be random. Depending on the
circumstance, priority could be given, for example, to children, or patients
most likely to have a cure, or those who are sickest.
Some advocates suggest that as
a matter of principle, children should have priority over adults. Certainly,
children should not be put at a disadvantage relative to adults.
The last question is whether
providing compassionate access would impose a substantial financial burden on a
company. Here again, the focus must be on finding solutions rather than
This could include a fund to
pay for the cost of producing, quality testing and distributing the compound,
and to pay companies to hire additional personnel to handle the
pharmacovigilance required by FDA.
Clearly, the judgments that
must be made to answer many of these questions are subjective, and they are
based in part on risk calculations that will be different depending on who
For example, many drug company
executives believe that compassionate access exposes drug development programs
to substantial regulatory risk, a contention that FDA officials and patient
advocates say is exaggerated.
Decisions about the effects of
compassionate access on a drug development program must give a great deal of
weight to the opinions of the company that is developing a drug. But to be
credible to patients, their physicians and the public, an independent entity
that does not have a financial interest should render an opinion.
In addition to taking some
steam out of allegations that companies are putting profits ahead of patients,
input from a trusted third party would shield drug company executives from
Similarly, when supply
limitations cannot be overcome, third parties - not drug companies - should
step in to develop and implement fair policies for allocating experimental
In light of the Josh Hardy case and another involving ovarian
cancer patient Andrea Sloan - both of which generated physical threats against
company employees - the third party idea is gaining some traction among patient
groups and companies, and has been mooted by New
York University ethicist Arthur Caplan as well.
The specific makeup of this
entity, how it should be funded and where it should be housed is a topic for
discussion. It needs to have representatives of industry, patients and
regulators. And it needs a mandate to call on advisors who have sufficient
expertise to make science-based decisions about the appropriateness of the
requested medicine for a particular patient.
Finally, the system will
require some sort of appeals process. It will be harder to wage protests if the
facts of the decision can be transparently reviewed and it can be confirmed the
rules were applied as intended.
The notion of an appeals
process also suggests that at least part of the compassionate use pathway
should be addressed through law and regulation. While some of the pathway
probably could be hammered out by patient groups and companies, there are
several reasons why it is likely that Congress will have to step in.
First, bipartisan legislation
would show that the new system reflects broad public consensus.
Second, the overall environment
for providing early access to experimental therapies would be improved by
passing laws that create incentives and remove disincentives to compassionate
For example, it may be necessary
to create a statutory safe harbor so that adverse event reports from use of a
compound in uncontrolled settings or in indications the sponsor isn't seeking
don't adversely affect FDA approval.
Finally, Congress would have to
authorize a public fund and allocate money towards it.
Companies that are developing
medicines have responsibilities to obtain regulatory approval as soon as
possible so their products can be disseminated as rapidly and widely as is
They also have a responsibility
to help people along the way, and if they lack resources needed to do so, to
seek those resources.
In the meantime, every company
would be well advised to adopt and make public a compassionate use policy if
its experimental drugs are likely to provide meaningful benefits over existing
products for life-threatening or serious conditions.
Some companies have already
For example, the Genentech
Inc. unit of Roche
states that compassionate access to investigational drugs is available to patients
if they have a serious, life-threatening illness, and have "exhausted all
available therapies typically used to treat the disease and [they are] no
longer responsive to, or able to tolerate, these treatments." Patients
must also have "no other viable therapy options, including participation
in ongoing relevant clinical trials."
Genentech also says it will
grant compassionate access only if it has "adequate supply of the
investigational medicine," and, in the U.S., if an institutional review
board (IRB) at the patient's treating hospital or clinic reviews and approves
the use of the medicine for the patient.
- Unsigned Commentary
represents BioCentury's Editorial viewpoint.
Inc. (NASDAQ:CMRX), Durham, N.C.
Inc., South San Francisco, Calif.
York University, New York, N.Y.
(SIX:ROG; OTCQX:RHHBY), Basel, Switzerland
Food and Drug Administration (FDA), Silver Spring, Md.